Low-density lipoprotein LTBI Latent tuberculosis (TB) infection MAC Mycobacterium avium complex MCV Mean corpuscular volume MHT Menopausal hormone therapy MI Myocardial infarction MMR Mumps, measles and rubella MRI Magnetic resonance imaging MSM Men who have sex with men MSP Medical services plan NAAT Nucleic acid amplification test NACI National Advisory Committee of Immunization (Canada) NASH Non-alcoholic steatohepatitis NNRTI Non-nucleoside reverse transcriptase inhibitor NRTI Nucleoside reverse transcriptase inhibitor NP Nurse practitioner OI Opportunistic infection# INTRODUCTION - 22
Figure 2.

# 1: The HIV Cascade of Care - 22
2.2 MODES OF HIV TRANSMISSION  

# - 2.3 NATURAL HISTORY OF HIV/AIDS - Figure 2.2: Natural history of HIV/AIDS. 
2.4 HIV TESTING 
RECOMMENDATIONS: - 3.

# INITIAL ASSESSMENT - Table 3.1: Initial assessment, medical history. - 3.2 PHYSICAL EXAMINATION 
Table 3.

# 2: HIV-related physical examination. - 3.3 BASELINE LABORATORY EVALUATION 
Table 3. 

# 3: Baseline laboratory assessment - 3.4 COUNSELLING PLWH REGARDING HIV TRANSMISSION RISK - 4 SCREENING AND IMMUNIZATION FOR SELECTED CO-MORBID INFECTIONS 

# SCREENING FOR CO-MORBID INFECTIONS - 4.2 IMMUNIZATIONS AND HIV - 4.2.1 Recommended Vaccines - Table 4.1: Recommended vaccines for adults living with HIV - 4.2.2 Additional Vaccines - 4.2.3 Contraindicated Vaccines - 5 SPECIAL CONSIDERATIONS FOR CISGENDER WOMEN LIVING WITH HIV (WLWH)

# INTRODUCTION - 5.2 SPECIAL CONSIDERATIONS RELATED TO ART DURING PREGNANCY AND THE POST-PARTUM PERIOD - 5.3 REPRODUCTIVE ISSUES AND GYNECOLOGIC HEALTH IN THE CONTEXT OF HIV - 5.4 ART AND WEIGHT GAIN IN WOMEN - 5.5 MENOPAUSE - 5.6 BONE HEALTH - 6 SPECIAL CONSIDERATIONS FOR TRANSGENDER INDIVIDUALS LIVING WITH HIV - 7 COMMON NON-INFECTIOUS CO-MORBIDITIES 

# INTRODUCTION - 7.2 CARDIOVASCULAR DISEASE - 7.3 INSULIN RESISTANCE (IR) AND DIABETES MELLITUS (DM) - 7.4 BONE - 7.5 RENAL DISEASE - 7.6 HYPOGONADISM - 7.7 NEUROCOGNITIVE IMPAIRMENT - 7.8 LUNG DISEASE 
7.9 LIVER DISEASE/CIRRHOSIS - 7.

# CANCER - 89 Table 7.1 Recommendations for cancer screening in PLWH - 7.11 MENTAL HEALTH - 8 SPECIAL CONSIDERATIONS FOR INDIVIDUALS WITH ADVANCED HIV -OPPORTUNISTIC INFECTION & PROPHYLAXIS 
-- 9.1 CHRONIC DISEASE MODEL OF CARE - 9.2 ACTIVE REFERRAL FOLLOWING DIAGNOSIS- Figure 9

# .1: The Chronic Care Model - 107 9.3 ADDRESSING SOCIAL DETERMINANTS OF HEALTH - 9.4 PEER-SUPPORT AND PATIENT OR PEER NAVIGATION - 9.5 CASE MANAGEMENT - 9.6 OUTREACH SERVICES - 9.7 OTHER SUPPORTS - APPENDIX 1: SIGNS AND SYMPTOMS ASSOCIATED WITH HIV SEROCONVERSION SYNDROME/ACUTE RETROVIRAL SYNDROME AND THEIR FREQUENCY IN SYMPTOMATIC INDIVIDUALS - APPENDIX 2: AIDS-DEFINING CONDITIONS - APPENDIX 3: SCREENING FOR NON-INFECTIOUS CO-MORBID CONDITIONS IN PEOPLE LIVING WITH HIV (PLWH) - APPENDIX 4: CONTACT LIST - PROVINCIAL AND REGIONAL HIV/AIDS SERVICE ORGANIZATIONS - 117 REGIONAL HEALTH AUTHORITY CONTACTS/ COMMUNICABLE DISEASE NURSING CONTACTS - 117 APPENDIX 5: OTHER GUIDELINES RELATED TO THE CARE OF PEOPLE LIVING WITH HIV (PLWH) - DISCLAIMER
No financial or in-kind commercial support has been received for the development of these guidelines; no commercial organization has supported the development of these guidelines. The content of the guidelines has been developed by the authors and reflect best practices in HIV care in British Columbia. Both positive and negative trials are mentioned where possible. Generic names of medications are used in place of brand names where possible.
These Guidelines represent the view of the Primary Care Guidelines Writing Committee, in consultation with an external group of experts and are based on available scientific evidence current to July 31, 2021. These Guidelines may be superseded by subsequent Guidelines. Please check  for the most recent Guidelines. Every health care professional is responsible for exercising their own professional skill and judgment and should consider these Guidelines in the context of the individual patient's circumstances, in consultation with that patient or their guardian(s), and when appropriate, external experts (e.g., specialty consultation). These Guidelines are not medical advice nor are they intended to be the only approach to the management of a clinical problem. These Guidelines should not be relied on by any individual as a substitute for the advice or professional judgment of a health care professional.

# WHAT'S NEW IN THE GUIDELINES

# Updated: November 2022
Toxoplasma Serology Table 3.3, Toxoplasma IgG serology, has been updated for agreement with the existing recommendations provided in the body of the Primary Care Guidelines. Toxoplasma IgG serology is indicated in all persons, regardless of CD4 cell count (Table 3.3). Previous versions stated toxoplasma IgG serology is indicated in persons with CD4 cell count <200 cells/mm3.

# INTRODUC TION
There has been a significant decrease in the morbidity and mortality of people living with HIV (PLWH) in the province of British Columbia since the introduction of potent antiretroviral treatment in 1996. According to the British Columbia Centre for Excellence in HIV/AIDS (BC-CfE) HIV Quarterly Monitoring Report for the fourth quarter of 2019, there were approximately 10,603 people in the province living with HIV.(1) Among them, around 7415 were receiving antiretroviral treatment in 2020. (2) The Primary Care Guidelines for the Management of HIV/AIDS in Adults in British Columbia, along with other therapeutic guidelines, have been developed by the BC-CfE to provide support for care and treatment programs for PLWH. These guidelines also respond to the need to expand HIV treatment to meet the goals of 90-90-90 in British Columbia and respond to requests from primary care providers in the community for HIV-specific guidelines.

# OBJECTIVES
- To provide consensus-based guidelines for the management of primary care for PLWH. 2. To provide practical and easily accessible information and resources for primary care providers of PLWH in the province of British Columbia.

# METHODS

# Process Overview and Committee Composition
An expert committee composed of primary care and infectious disease physicians, a nurse practitioner, a pharmacist, and a person living with HIV prepared the original guidelines in 2011. Since the guidelines were first published, they have been consistently reviewed and revised to ensure that the information is up-to-date. In 2014/15, the original expert committee collectively undertook a review of the 2011 guidelines. The most recent review was finalized in 2021 by a review committee consisting of primary care, public health, and infectious disease physicians (refer to above). Where applicable, the committee updated epidemiology, baseline assessment, immunizations, and co-morbidities data and added new recommendations. The revisions were sent out to subject matter experts for review where necessary.

# Consensus Development on the Basis of Evidence
The review committee met a total of eight times. Committee members developed sections, in consultation with external medical experts where appropriate, and presented their work at committee meetings, where all recommendations were discussed until consensus was reached. The final manuscript was reviewed by all committee members and then presented to and reviewed by members of the Committee for Drug Evaluation and Therapy (CDET) at the BC-CfE and reviewed by external reviewers (listed above).
Each recommendation in the guidelines has been assigned a level of evidence based on the GRADE criteria (refer to Table 1.
Note that this method of grading recommendations is different from previous versions of the BC-CfE Primary Care Guidelines. 

# Quality of Evidence Definition
A High
Further research is very unlikely to change our confidence in the estimate of effect.
Several high-quality studies with consistent results
In special cases: one large, high-quality multi-centre trial

# B Moderate
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
One high-quality study Several studies with some limitations

# C Low
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
One or more studies with severe limitations

# D Very Low
Any estimate of effect is very uncertain.

# Expert opinion
No direct research evidence One or more studies with very severe limitations 

# WLWH
Women living with HIV

# X-ray
Penetrating form of high-energy electromagnetic radiation

# SUMMARY OF PRIMARY CARE RECOMMENDATIONS FOR THE MANAGEMENT OF HIV/AIDS INITIAL ASSESSMENT OF PEOPLE LIVING WITH HIV (PLWH)
- All PLWH should have timely access to a primary care clinician with knowledge in the management of HIV infection and should receive care in a culturally sensitive environment. Primary care clinicians without expertise in HIV care should consult with a physician with this expertise. (D)
- All patients entering HIV care should have documented evidence of HIV antibody testing. If laboratory confirmation is not available, a repeat HIV antibody test should be performed. (D) 3. Clinicians should obtain a comprehensive present and past medical history, including HIV-related information, assessment of present medications, family history and psycho-social issues, and review of systems and conduct a complete physical examination upon the patient's entry into care. (D) 4. A baseline CD4 cell count (absolute and fraction) and quantitative HIV RNA (plasma viral load) should be done for all patients upon entry into care. (A) 5. All patients should be assessed for transmitted HIV drug resistance using genotypic drug resistance testing. Ideally, the drug resistance testing should be conducted on the first available sample of HIV plasma viral load. (B) 6. HLA-B*5701 testing is recommended once at baseline for all patients. HLA-B*5701-positive patients must not be given abacavir-containing regimens. (A) 7. Hematology (CBC with differential and platelet count) and comprehensive biochemistry (liver and renal function, lipid profile, fasting blood glucose and/or HbA1C) is recommended at baseline to support management of ART toxicities and to evaluate other potential co-morbidities. (D) 8. A chest X-ray should be performed at baseline in all PLWH. (D) 9. All patients should receive baseline screening for a variety of other infectious agents to assess the need for immunization, monitoring, and counselling (see Section 4, Screening and Immunization for Selected Co-Morbid Infections). (D) 10. PLWH should be advised of the risk of onward transmission, the effectiveness of HIV treatment in preventing transmission, other practices to prevent transmission, and the legal implications of HIV non-disclosure with their sexual partners. (D)

# SCREENING AND IMMUNIZATION FOR SELECTED CO-MORBID INFECTIONS
Tuberculosis Screening
- All PLWH should be screened at baseline for Mycobacterium (M.) tuberculosis (TB) infection. (A) Screening involves reviewing history of TB exposure and/or treatment history and previous tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) results. (B) A chest X-ray should be undertaken if there is history of TB exposure or positive screening test. (B) 2. In BC, the TST using 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) is the main test for diagnosing latent TB infection (LTBI), provided there are no contraindications. (B)
- IGRAs are currently recommended as an adjunct test to TST and may be valuable in the following two situations: a) PLWH with CD4 cell count <200 cells/mm 3 who are TST-negative (if possible, the T-SPOT assay is preferred); and b) PLWH with a history of contact with active TB and who are TST-negative. (C)

# Toxoplasmosis Screening
- All PLWH should be screened at baseline for Toxoplasma IgG antibodies to determine prior exposure to Toxoplasma (T.) gondii. (D)

# Hepatitis Screening
- PLWH should be screened at baseline for hepatitis A virus (HAV) using total anti-HAV antibodies. (B)
- PLWH should be screened at baseline for hepatitis B virus (HBV) using HBsAg (hepatitis B surface antigen), anti-HBs (hepatitis B surface antibody), and anti-HBc (hepatitis B core antibody). (B) 

# Screening for Syphilis and Other Sexually Transmitted Infections (STIs)
- All PLWH should be screened for syphilis at baseline with Treponema pallidum-specific enzyme immunoassay (EIA). (B) Syphilis screening should be repeated annually, or every 3-6 months in the presence of ongoing risk behaviours, or in the presence of symptoms. (D)
- A lumbar puncture should always be performed for patients with a reactive syphilis serology who have neurologic or ocular symptoms or signs, irrespective of past syphilis treatment history. (D)
- All PLWH should be screened at baseline for gonorrhea and chlamydia. (B) Screening should occur every 3-6 months in the presence of ongoing risk behaviours or in the presence of symptoms. (D)

# Recommended Vaccines
Hepatitis A
- All PLWH who are susceptible (anti-hepatitis A  negative) should be vaccinated against HAV, ideally when CD4 >200 cells/mm 3 . (B)
- The HAV vaccine should be administered intramuscularly at the standard dose, at 0, 1, and 6 months. (B)

# Hepatitis B
- All PLWH who are susceptible to hepatitis B virus (HBV) infection (HBsAg negative and anti-HBs less than 10 IU/mL) should be vaccinated against HBV, ideally when CD4 >200 cells/ mm 3 . (B)
- HBV vaccination should also be offered to PLWH who have positive hepatitis B total core antibody (anti-HBc) with negative HBsAg and anti-HBs results (titre less than 10 IU/mL) and undetectable HBV DNA. (D)
- In the situations described above, HBV vaccine should be administered intramuscularly (IM) to PLWH 20 years of age and older at a higher dose (40 mcg).
- Recombivax HB (10 mcg/mL): give 4.0 mL IM at 0, 1, and 6 months (B)
- Recombivax HB  Adult Dialysis formulation (40 mcg/mL) give 1.0 mL IM at 0, 1, and 6 months (B)
- Engerix-B Adult (20 mcg/mL): give 2.0 mL IM at 0, 1, 2, and 6 months (B)
- Post-serologic testing (using anti-HBs) within 1-6 months of completion of the vaccine series is recommended to monitor success of immune response to vaccine. (B)

# Pneumococcal Disease
- All PLWH should be vaccinated against pneumococcal disease using standard vaccine doses (A), regardless of CD4 cell counts and according to the following schedules: (i) Individuals who have not previously received any pneumococcal vaccine: One dose of conjugate pneumococcal vaccine (Pneu-C-13) is followed at least 8 weeks later by one dose of polysaccharide pneumococcal vaccine (Pneu-P-23). (B) (ii) Individuals who have received a pneumococcal polysaccharide vaccine (Pneu-P-23) previously: The Pneu-C-13 dose should be administered at least one year after any previous dose of Pneu-P-23. (C) (iii) If re-immunization with Pneu-P-23 is needed, it should be given at least 8 weeks after the Pneu-C-13 dose and at least 5 years after the initial Pneu-P-23 dose. (C)

# Influenza
- All PLWH should be vaccinated annually against influenza using standard doses of the inactivated vaccine, regardless of CD4 cell counts or HIV plasma viral load. (B)

# Tetanus and Diphtheria
- All PLWH should be offered a tetanus and diphtheria (Td) toxoid booster every 10 years, ideally when CD4 >200 cells/mm 3 . (D)

# Human Papillomavirus (HPV)
- HPV-9 vaccine is recommended for all PLWH aged 9-27 years (A) and should be strongly considered in women and MSM aged 27 years and older. (B) A three-dose series is recommended in adults.

# Additional Vaccines
Measles, Mumps, and Rubella (MMR)
- All PLWH without evidence of immunity and with CD4 cell counts >200 cells/mm 3 should be considered for measles and/or mumps and/or rubella vaccination (given as a two-dose series of MMR vaccine). (B)

# Varicella
- All PLWH without evidence of immunity and with CD4 cell counts >200 cells/mm 3 may be considered for varicella vaccination (given as a two-dose series of varicella vaccine given >3 months apart). (D)
Herpes Zoster 

# Hypogonadism
- Cisgender men living with HIV presenting with symptoms of hypogonadism should be assessed with a morning serum total testosterone level; an abnormal testosterone level should be confirmed with repeat testing. (B) An estimated bioavailable testosterone measurement may be helpful to assess certain individuals, including obese cisgender men with borderline low total testosterone levels. (B)
- Testosterone replacement is indicated only for symptomatic cisgender men with total testosterone levels less than 10 mmol/L (B) and should be prescribed in consultation with a specialist. (D)
- Endocrine therapy for transgender individuals living with HIV should be provided in consultation with an endocrinologist or other clinician who has experience providing endocrine care to transgender individuals. (D)

# Neurocognitive Impairment
- ART to suppress plasma viral load should be started early and administered continuously to prevent or minimize HIV-related neurocognitive impairment. (B)
- In PLWH presenting with cognitive complaints that affect their daily functioning, an investigation should be done to rule out relevant underlying conditions. (B)

# Lung Disease
- Smoking cessation should be strongly encouraged in all PLWH because they are at a higher risk for chronic obstructive pulmonary disease (COPD) and lung cancer than smokers who do not have HIV. (A)
- A chest X-ray should be performed at baseline in all PLWH. (D) Once infection has been treated or ruled out, patients with persistently abnormal chest X-ray findings should be investigated and referred to a respiratory specialist if necessary. (D) 

# Mental Health
- Mental health should be proactively assessed during clinic visits, and identified conditions should be managed using a stepped-care approach. (D)

# BACKGROUND

# INTRODUCTION
Today, HIV infection is a chronic manageable medical condition. Early diagnosis and initiation of potent antiretroviral therapy (ART) has dramatically improved the management of HIV infection and has led to substantial reductions in HIV-related morbidity and mortality.(1, 2) A study from 2013 estimated that a 20-year-old living with HIV and receiving ART in the U.S. or Canada could expect to live into their early 70s, a life expectancy approaching that of the general population.(3) In addition, there is now clear evidence that the widespread use of ART prevents HIV transmission at the individual (4-6) and population level. (7)(8)(9) In order for ART to be effective, individuals must be fully engaged in care, from the initial assessment following diagnosis, in order to receive timely initiation of ART and achieve long-term retention in care and virologic suppression. This concept, known as the HIV Cascade (or Continuum) of Care (10) has been adopted as the framework for assessing progress in HIV care and treatment in BC (Figure 2.1) and more generally as the 90-90-90 targets promoted by UNAIDS. (11) As of the end of 2018, an estimated 92% of people living with HIV (PLWH) in BC were diagnosed, 91% of those diagnosed were receiving ART, and of those on ART, 94% had a measured HIV viral load <200 copies/mL. (12) Providing appropriate and accessible primary care services is key to helping PLWH to remain fully engaged in HIV care and treatment. 

# MODES OF HIV TRANSMISSION
The key modes of HIV transmission -sexual contact, perinatal transmission, and exposure to infected blood (e.g. through sharing of injection drug paraphernalia or receipt of contaminated blood products) -were clarified early in the AIDS epidemic. In untreated PLWH, HIV is present in significant concentrations in blood, semen, vaginal and rectal fluids, breast milk, and other body fluids contaminated with blood. However, the likelihood of HIV transmission by different routes of exposure varies markedly, as shown in  

# NATURAL HISTORY OF HIV/AIDS
The mean time from HIV exposure to onset of acute seroconversion illness is generally 2-4 weeks, with a range of 5-29 days (19), and only an estimated 34% of PLWH will experience symptomatic seroconversion illness (see Appendix 1, page 112: Signs and symptoms associated with HIV Seroconversion Syndrome/ Acute Retroviral Syndrome and their frequency in symptomatic individuals). (20) During seroconversion without ART, there is an initial drop in CD4 cell counts and peak of viremia before CD4 cell counts increase (although to levels typically below pre-infection levels) and viral load decreases and stabilizes at a set point for several years (Figure 2.2). Without ART, there is considerable variability in the time of onset of further symptoms and late-stage disease. People whose CD4 cell counts stabilize above 500 cells/mm 3 may remain healthy for several years before CD4 cell counts begin to decline. In some cases, CD4 cell counts can drop rapidly after infection in the absence of ART; however, the usual scenario is that without treatment, CD4 cell counts decline over approximately 5-8 years until symptoms begin to appear. A small proportion of PLWH (5-10%), called "long-term non-progressors, " will maintain low viral load and stable CD4 cell counts for decades without specific treatment.( 21 However, timely initiation of ART will effectively prevent disease progression. In previous eras, HIV treatment was often deferred until PLWH demonstrated some degree of disease progression; however, there is now clear evidence that treating PLWH immediately after diagnosis provides substantial clinical benefits and this should be emphasized at all clinical encounters. Evidence:

# HIV TESTING
Newly diagnosed individuals should be assessed by a primary care physician or nurse practitioner (NP) within a few days of receiving a positive HIV test result (ideally less than 2 weeks) so that the baseline laboratory workup can be ordered and the individual can receive appropriate counselling and rapid initiation of antiretroviral treatment (ART 

# INITIAL ASSESSMENT
Clinicians should obtain a comprehensive present and past medical history, including HIV-related information, assessment of present medications, family history and psychosocial issues and review of systems. A complete physical examination should be performed upon the patient's entry into care or as soon afterwards as possible. In the setting of rapid ART initiation, clinicians may abbreviate the initial assessment and conduct a more targeted exam. A more comprehensive assessment should be done in follow-up.
Important elements of the initial assessment are included in  In the course of taking a medical history, health care providers should also assess the individual's understanding of HIV disease (including risk for HIV transmission), explore their understanding of and readiness to initiate ART, note potential barriers to treatment adherence, and identify their psychosocial needs. The baseline evaluation should also include a discussion of risk reduction and disclosure to sexual and/or needle-sharing partners, especially with individuals who are not receiving HIV treatment and are still at high risk of HIV transmission (see Section 3.4).

# PHYSICAL EXAMINATION
Clinicians should perform a comprehensive physical examination at baseline and when appropriate, with particular attention to systems potentially affected by HIV (see Table 3 

# BASELINE LABORATORY EVALUATION
Two main surrogate markers are used to monitor the disease progression in PLWH: CD4 cell count to assess immune function and plasma HIV RNA (viral load) to assess level of HIV viremia.
The absolute CD4 cell count is a significant clinical indicator of immunocompetence in PLWH.( 9) It is a calculated value based on the total white blood cell (WBC) count and the percentages of total and CD4 T-lymphocytes. (10) This absolute number may fluctuate in individuals or may be influenced by factors that affect the total WBC count and lymphocyte percentages, such as the use of bone marrow-suppressive medications or the presence of acute infections. Splenectomy or co-infection with human T-lymphotropic virus type 1 (HTLV-I) may cause misleadingly elevated CD4 cell counts. These markers are used to stage HIV disease initially and are subsequently used as predictors of disease progression and survival.(11) CD4 cell counts are also used to determine the risk of opportunistic infections (OIs), the need for prophylaxis for OIs or other AIDS-defining illnesses, and when to stop prophylaxis. (12,13) HIV plasma viral load (HIV pVL) is the most important indicator of infectivity and response to ART and should be measured in all PLWH at initial assessment, at initiation of therapy and on a regular basis thereafter.(12) A patient's baseline viral load level and the magnitude of viral load decline after initiation of ART provide prognostic information about the probability of disease progression.( 14) Commercially available HIV-1 RNA assays do not detect HIV-2 viral load (for more information regarding HIV-2 refer to the HIV-2 infection chapter in the United States Department of Health and Human Services (DHHS) guidelines; . hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf). (15) All patients should be assessed for transmitted HIV drug resistance using genotypic drug resistance testing, regardless of the estimated duration of HIV infection. Ideally, drug resistance testing should be conducted on the first available sample of HIV plasma viral load. A resistance test should be done in individuals who reengage in care and are not currently receiving ART, recognizing that the absence of resistance mutations due to lack of selective pressure may not accurately reflect drug activity.(15) Standard genotypic drug resistance testing in ART-naive persons involves testing for mutations in the reverse transcriptase and protease genes. Although reports of transmission of virus resistant to integrase strand transfer inhibitors (INSTIs) are rare, clinicians are increasingly prescribing this class of antiretrovirals and there is potential for the transmission of INSTI-resistant virus. (16)(17)(18)(19) In BC, when HIV resistance testing is requested for a patient whose plasma viral load exceeds 250 copies/mL for the first time since diagnosis, the sample automatically undergoes testing for resistance to the INSTI class. (11) In BC, resistance testing can be requested in archived viral load samples. For more information regarding drug resistance testing, refer to the Laboratory Program tab on the BC-CfE website (/ laboratory-test-order-forms).
HLA-B*5701 is not a specific HIV test, but rather a genetic test. Screening for HLA-B*5701 identifies persons at a high risk for hypersensitivity reaction (HSR) to the antiretroviral agent abacavir. Screening should be performed prior to starting any patient on an abacavir-containing regimen (including fixed-dose combinations, e.g. Kivexa, Triumeq). HSRs, including fatalities, have been documented in individuals re-challenged with abacavir after a suspected HSR. In addition, screening for HLA-B*5701 should be performed, if not done previously, for patients who are re-initiating abacavir following a gap in therapy, even if they had previously tolerated the drug, because there is a potential for HSR in this setting. (20,21) Hematological panel (CBC with differential and platelet count) should be done at baseline since anemia, leukopenia and thrombocytopenia are common in people with untreated HIV infection. A comprehensive chemistry panel (including creatinine, eGFR, serum phosphorus, urinalysis, urine albumin to creatine ratio (UACR), albumin, total bilirubin, aspartate transaminase, and alanine transaminase) is important to assess baseline renal and hepatic function and pre-existing conditions. Screening for diabetes mellitus with fasting glucose and/or hemoglobin A1C is recommended due to the increased incidence of diabetes in this population. A lipid profile should be done upon initial assessment when possible, since many ART drugs, HIV infection itself, and other host factors can increase cholesterol and triglyceride levels.
A chest radiography should be done at baseline to rule out underlying lung disease and for use as a baseline comparison in future evaluations of any respiratory illness, particularly in persons from high TB prevalence populations (see Table 3.
All individuals should receive baseline screening for a variety of other infectious agents, including other sexually transmitted infections and hepatitis A, B, and C virus, to assess the need for treatment, immunization, monitoring, and counselling (see Section 4). Rates of sexually transmitted infections have increased significantly in men who have sex with men, and screening at baseline for gonorrhea and chlamydia in urine and other sites of contact (oral and anal) are recommended. Furthermore, all PLWH should receive a syphilis test at baseline.  

# COUNSELLING PLWH REGARDING HIV TRANSMISSION RISK
Recommendation:
- PLWH should be advised of the risk of onward transmission, practices to prevent transmission, especially the effectiveness of HIV treatment in preventing transmission, and the legal implications of HIV non-disclosure with their sexual partners.

# Evidence:
Safer sex and substance use practices to prevent onward transmission of HIV should be discussed with PLWH, and are especially important while the plasma HIV viral load is high (e.g. prior to starting ART and during the first few weeks of therapy or when there is treatment interruption). It has now been clearly demonstrated that even after repeated sexual exposures without using condoms, PLWH who are adherent to ART and have HIV plasma viral load <200 copies/mL do not transmit HIV via sexual contact. This principle of "undetectable = untransmittable" or "U=U" has been shown for both heterosexual couples and men who have sex with men.(24-28) However, the Supreme Court of Canada (2012) ruled that there is an obligation to disclose HIV-positive status in relation to vaginal or anal sex unless both of the following conditions are met: a condom is used and the PLWH has "low" viral load (<1500 copies/mL). Under these circumstances, the Supreme Court of Canada holds that there is no realistic possibility of transmission. If PLWH were to engage in sexual activity that is considered to have a "realistic possibility of HIV transmission" without first disclosing their HIV status, they can be subject to criminal prosecution (most often aggravated sexual assault). (29,30) PLWH should be advised of the legal implications of HIV non-disclosure. Further information for PLWH is available from: 

# SCREENING AND IMMUNIZATION FOR SELEC TED CO-MORBID INFEC TIONS 4.1 SCREENING FOR CO-MORBID INFECTIONS
Tuberculosis Screening Recommendations:
- All PLWH should be screened at baseline for Mycobacterium (M.) tuberculosis (TB) infection.
(A) Screening involves reviewing history of TB exposure and/or treatment history and previous tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) results. (B) A chest X-ray should be undertaken if there is history of TB exposure or positive screening test. (B)
- In BC, the TST using 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) is the main test for diagnosing latent TB infection (LTBI), provided there are no contraindications. (B) The tuberculin skin test (TST), consisting of the intradermal injection of a small amount of purified protein derived from M. tuberculosis bacteria, is the standard screening test for TB. In a person who has cell-mediated immunity to these tuberculin antigens, a cell-mediated, delayed hypersensitivity reaction will occur within 48-72 hours. The reaction will cause localized swelling and will manifest as induration of the skin at the injection site. Induration of 5 mm is considered significant in PLWH.(1) TST remains the standard method of diagnosing LTBI(1) in Canada, although it is recognized that TST has certain limitations. The sensitivity of the TST decreases in parallel with an individual's CD4 cell count. The TST has particularly low sensitivity in people with CD4 <200 cells/mm 3  Positive TST results should be followed by treatment for LTBI, once active TB disease is ruled out, through referral to provincial TB Services offered by the BCCDC.

# Toxoplasmosis Screening
Recommendation:
- All PLWH should be screened at baseline for Toxoplasma IgG antibodies to determine prior exposure to Toxoplasma (T.) gondii. (D)

# Evidence:
Seroprevalence of T. gondii in North American adults is approximately 10-20%. Toxoplasma encephalitis (TE) is the most frequent clinical manifestation of central nervous system (CNS) disease in PLWH. (15) The serologic test for Toxoplasma cannot be used to diagnose or reliably exclude toxoplasmosis in PLWH. (12) Positive serology identifies individuals at a greater risk of disease. Peripheral blood serology is positive for Toxoplasma IgG (but negative for IgM) in the vast majority of patients with AIDS-related TE. However, in one study from San Francisco, 16% of those presenting with AIDS-related TE had negative serum serology for IgG by immunofluorescence.(15) Among T. gondii-infected (i.e. Toxoplasma IgG antibody positive) adult PLWH not receiving prophylaxis and with CD4 cell counts <100 cells/mm 3 , the probability of developing clinical toxoplasmosis is approximately 38%.( 12)

# Hepatitis Screening
Recommendations:
- PLWH should be screened at baseline for hepatitis A virus (HAV) using total anti-HAV antibodies. (B) HIV and hepatitis B virus (HBV) share routes of transmission, including percutaneous (principally among people who inject drugs ), sexual (anal, vaginal, and oral) and vertical transmission. (16) The reported prevalence of HIV-HBV co-infection is between 6-10%, with higher rates observed in PWID, MSM, and individuals from endemic areas.(20) HIV-HBV co-infection is associated with an eight-fold increase in risk of mortality compared to HBV mono-infection.( 21) Therefore, traditional HBV markers, such as HBsAg (surface antigen), anti-HBs (surface antibodies), and anti-HBc (core antibodies), will assist in distinguishing individuals who are chronically infected from those who have developed a natural or acquired immune response or those susceptible to HBV infection (thus, in need of receiving immunization).
Assessment for liver disease from chronic HBV infection and screening for hepatocellular carcinoma should follow standard Canadian guidelines.( 22) However, all PLWH with chronic HBV infection should be offered ART including tenofovir disoproxil fumarate (DF) or tenofovir alafenamide (AF) in combination with emtricitabine in order to control HBV viral replication.
In Canada, the prevalence of HIV-hepatitis C (HCV) co-infection ranges from 20% to almost 90% in certain subgroups.( 23) HCV is highly prevalent among PWID; a review of international studies suggests that between 50-95% of PWID are infected with HCV. (24) Canadian studies report HCV rates as high as 82% among PWID. (25,26) If left untreated, HCV infection becomes chronic in up to 85% of co-infected individuals, potentially leading to progressive fibrosis and ultimately cirrhosis and death.(24) A metaanalysis of seventeen studies concluded that the rate of progression to hepatic fibrosis among individuals co-infected with HIV-HCV appears constant across all stages of fibrosis, and that chronic HCV outcomes are worse among co-infected individuals. Over the period studied, ART did not appear to fully reverse the adverse effect of HIV infection on HCV disease prognosis. (27) The probability of survival is also reduced among HIV-HCV co-infected individuals compared to those who are HIV mono-infected.( 28 

# Screening for Syphilis and other Sexually Transmitted Infections (STIs)
Recommendations:
- All PLWH should be screened for syphilis at baseline with Treponema pallidum-specific enzyme immunoassay (EIA). (B) Syphilis screening should be repeated annually, or every 3-6 months in the presence of ongoing risk behaviours, or in the presence of symptoms. (D)
- A lumbar puncture should always be performed for patients with a reactive syphilis serology who have neurologic or ocular symptoms or signs, irrespective of past syphilis treatment history. (D)
- All PLWH should be screened at baseline for gonorrhea and chlamydia. (B) Screening should occur every 3-6 months in the presence of ongoing risk behaviours or in the presence of symptoms. (D)

# Evidence:
In North America, sexual transmission is the predominant route for acquiring HIV. This has prompted the recommendation to screen all PLWH for asymptomatic sexually transmitted infections (STIs). A cohort study reported a baseline STI prevalence of 14% among PLWH (n=212, 95% confidence interval  9%-19%) and the incidence of new infections was 20.8 cases per 100 person-years (95% CI 14.8-28.4).( 31)
The prevalence of STIs in British Columbia is increasing. The provincial prevalence of infectious syphilis, as elsewhere in North America, has increased over the past fifteen years. With the exception of a short period of decline in 2009-2010, infectious syphilis rates have increased steadily to 14. A lumbar puncture should always be performed for patients with a reactive syphilis serology who have neurologic or ocular symptoms or signs, irrespective of past syphilis treatment history. In asymptomatic patients, a lumbar puncture may be considered for those patients with an RPR titre of > 1:32 or a CD4 of < 350 cell/mm 3 , which are laboratory criteria that improve the ability to identify asymptomatic neurosyphilis.(34) However, studies defining the clinical outcomes associated with a broader versus more narrow utilization of lumbar puncture in asymptomatic PLWH with syphilis have not been conducted.
For gonorrhea and chlamydia, a Nucleic Acid Amplification Test (NAAT) should be conducted at baseline in all PLWH using first-catch urine specimen and site-specific testing as indicated (oropharyngeal and rectal swabs) for MSM and others with potential sexual exposure at these sites. The validated multisite APTIMA swab is recommended for use (as opposed to the urethral/cervical swab). In PLWH who have a cervix, a cervical swab could be taken. Although not validated, vaginal swabs can be used for screening in transfeminine individuals who are post-operative (i.e. after gender-affirming surgery). In cases of possible sexual assault, pharyngeal, anal, and/or vaginal swabs should be taken. (35) Prevalent and incident asymptomatic STIs are common among MSM living with HIV, and thus increasing the frequency of screening to every 3-6 months is warranted for those with ongoing risk for infection (i.e. ongoing sexual activity with casual or multiple partners).

# IMMUNIZATIONS AND HIV
Prevention of intercurrent illness is a crucial aspect of HIV care. (29,36) The use of vaccines provides an opportunity to prevent infectious diseases in PLWH, who are more susceptible to these diseases. (17) Immunosuppression can reduce the effectiveness of vaccines and increase the risks associated with live vaccines. (17,19,37) CD4 cell counts are an important measure that can be used to help optimize the timing of immunizations and predict patient response to vaccines -in general, if a PLWH has a CD4 cell count 200 cells/mm 3 they will have a better response to vaccination.
General principles that primary care providers can follow for PLWH are shown below (adapted from the BCCDC Immunization Guide and the Canadian Immunization Guide)(17):
- Immunize at the time when maximum immune response can be anticipated (i.e. early in the course of HIV disease or following CD4 recovery with antiretroviral therapy).
- It is safer, and likely more effective, to immunize when CD4 cell counts are >200 cells/mm 3 .
- Use caution in the use of live vaccines based on CD4 cell counts.
- Use of the measles, mumps, and rubella (MMR) and varicella vaccines in those with CD4 <200 cells/mm 3 is not recommended.
- There is no contraindication to the use of inactivated or component vaccines at any CD4 level.

# RECOMMENDED VACCINES

# Hepatitis A
Recommendations:
- All PLWH who are susceptible (anti-hepatitis A  negative) should be vaccinated against HAV, ideally when CD4 >200 cells/mm 3 . (B)
- The HAV vaccine should be administered intramuscularly at the standard dose, at 0, 1, and 6 months. (B)

# Evidence:
Serologic response rates of all HAV vaccines are between 95-100% amongst HIV-negative individuals.(17) Seroconversion rates are lower among PLWH for many vaccines and HAV seroconversion is no exception, with rates ranging from 48-64% (depending on the timing of measurement of serological response). (38,39) A meta-analysis reported an overall response rate of 64% for PLWH.(40) A three-dose regimen (at 0, 1, 6 months) has been shown to have better results than a two-dose regimen (at 0 and 6 months) among PLWH, with one comparative study reporting seroconversion rates of 78% and 61%, respectively.(41) The standard HAV vaccination doses are 1.0 mL intramuscularly (IM).( 37)

# Hepatitis B
Recommendations:
- All PLWH who are susceptible to hepatitis B virus (HBV) infection (HBsAg negative and anti-HBs less than 10 IU/mL) should be vaccinated against HBV, ideally when CD4 >200 cells/ mm 3 . (B)
- HBV vaccination should also be offered to PLWH who have positive hepatitis B total core antibody (anti-HBc) with negative HBsAg and anti-HBs results (titre less than 10 IU/mL) and undetectable HBV DNA. (D)
- In the situations described above, HBV vaccine should be administered intramuscularly (IM) to PLWH 20 years of age and older at a higher dose (40 mcg).

# Evidence:
The overall seroconversion rate (defined as Anti-HBs >10 mIU/mL) to standard HBV vaccine dosing (10 mcg of Recombivax HB or 20 mcg of Engerix-B IM ) following a 0, 1, and 6 month dosing regimen appears to be on the order of 26-65%. (17,(42)(43)(44) The etiology of poor seroconversion rates in PLWH is multi-factorial and not completely elucidated. Contributing factors may include age, sex, race, CD4 cell count (both nadir and at time of vaccination), HIV viral load, treatment with antiretrovirals, smoking and alcohol abuse. The benefit of using higher doses of HBV vaccine in immunocompromised individuals is now well-established, both in HIV and in other immunodeficiency states. (42,45,46) In particular, higher HBV seroconversion rates are reported in PLWH on antiretroviral therapy (ART) with low HIV plasma viral load and high CD4 cell counts. The low seroconversion rate is an indication to conduct post-vaccination testing (HBsAg and anti-HBs) on one occasion, between 1 and 6 months after the completion of the initial vaccination series. (47) PLWH with isolated antibody to hepatitis B core antigen (HBsAg negative and surface antibody titre 10 IU/mL has been documented, no further testing or vaccination is required, even if a later measurement is found to be <10 IU/mL.
Vaccine non-responders following the first series should receive a complete second series of three doses.
If they fail to respond to a second series, they should be recorded as susceptible and receive hepatitis B immune globulin (HBIg) following a high risk hepatitis B exposure.( 49)

# Pneumococcal Disease
Recommendations:
- All PLWH should be vaccinated against pneumococcal disease using standard vaccine doses (A), regardless of CD4 cell counts and according to the following schedules: While one study comparing Pneu-C-7 to Pneu-P-23 found that the conjugated vaccine elicited better serologic response,( 66) other studies have looked into possible synergistic effect of a dual vaccination regimen that incorporates both the conjugate and the polysaccharide vaccines, with the conjugate vaccine used first as an immune primer. (67)(68)(69)(70)(71) In addition, the sequence of vaccination is important, as initial receipt of Pneu-P-23 followed by conjugate vaccine results in lower antibody levels than initial vaccination with the conjugate vaccine.( 72) PLWH who receive the polysaccharide vaccine first should have delayed administration of the conjugate vaccine at least 12 months later. The National Advisory Committee on Immunization (NACI) concluded that there is good evidence to recommend the use of Pneu-C-13 for PLWH, given the efficacy and immunogenicity of Pneu-C-7.(73) The Pneu-C-13 vaccination dose is 0.5 mL IM and the Pneu-P-23 vaccination dose is 0.5 mL (subcutaneously  or IM), although SC administration is associated with more discomfort at the injection site.(37)

# Influenza
Recommendation:
- All PLWH should be vaccinated annually against influenza using standard doses of the inactivated vaccine, regardless of CD4 cell counts or HIV plasma viral load. (B)

# Evidence:
Caused by influenza A and B viruses, influenza occurs in Canada every year, generally during late fall and the winter months. Influenza A viruses are the most common cause of annual influenza epidemics. (17) The annual incidence of influenza varies widely, depending on the virulence of circulating strains and the susceptibility of the population, which is affected by antigenic changes in the virus, vaccine match, and vaccine coverage.(17) PLWH form part of the group at the greatest risk of serious infections, complications, hospitalizations, and/or death from influenza. (17,74) In PLWH, influenza vaccine reduces the incidence of respiratory illnesses from 49% to 29% and of laboratory-confirmed influenza from 21% to 0%. (75) As is the case with other vaccines, influenza vaccine efficacy is impaired in PLWH. One study estimated that vaccine efficacy decreased from 65% in PLWH with CD4 cell counts >100 cells/mm 3 to 11% in those with lower CD4 cell counts.(76) However, the benefits of the influenza vaccine in preventing severe illness and hospital/intensive care unit admissions prompted the US Centers for Disease Control (CDC) to recommend the use of the vaccine in PLWH, regardless of CD4 cell counts or HIV plasma viral load. (77) A single annual IM dose of 0.5 mL is currently recommended. (17,37) There is no indication for pre-or post-immunization serology testing.(17) Inactivated influenza vaccine is recommended and live attenuated intranasal vaccine should not be used in this population. (19,29,37,78) Influenza vaccines publicly funded in British Columbia vary year to year. For details of which vaccines are being used in any given season, refer to the BCCDC's Immunization Manual ().( 79)

# Tetanus and Diphtheria
Recommendation:
- All PLWH should be offered a tetanus and diphtheria (Td) toxoid booster every 10 years, ideally when CD4 >200 cells/mm 3 . (D)

# Evidence:
The recommendation above is based on the assumption that the diphtheria vaccine is being offered to an adult who has completed a primary series of childhood vaccinations. Routine immunization against diphtheria in infancy and childhood is a common practice throughout the world and has contributed to a significant decline in morbidity and mortality from this disease.(80) Serosurveys of healthy adult populations in Canada indicate that approximately 20% of those surveyed (higher in some age groups) do not have protective levels of antibody to diphtheria. Thus, the potential for re-emergence of this disease exists.( 81)
The immunity conferred by diphtheria vaccine is antitoxic, not antibacterial. Vaccination thus protects against the systemic effects of diphtheria toxin but not directly against local infection.(81) After the primary vaccination series in immunocompetent individuals, over 99% develop antibody levels that are considered protective against disease. (80) The antitoxin is believed to persist at protective levels for 10 years or more. Titres decline slowly with time but are boosted by additional vaccine doses. (80) Tetanus is rare in Canada. However, serosurveys suggest that a substantial proportion of Canadians have non-protective tetanus antitoxin levels. Factors associated with lack of immunity to tetanus include increasing age, birth outside Canada, and absence of immunization records. (81) The antibody response to tetanus boosters given to adults living with HIV or other humoral immune deficiencies is suboptimal.(80)

# Human Papillomavirus (HPV)
Recommendation:
- HPV-9 vaccine is recommended for all PLWH aged 9-27 years (A) and should be strongly considered in women and MSM aged 27 years and older. (B) A three-dose series is recommended in adults.

# Evidence:
Human papillomavirus (HPV) is a sexually transmitted pathogen that causes ano-genital disease in all sexes. HIV-mediated immune suppression appears to facilitate HPV persistence and its oncogenic potential. In part, this appears to be due to direct enhancement of HPV integration in the presence of HIV.( 82)
In an international study, 77% of women living with HIV (WLWH) had HPV detected at least once (incident infection). HPV 16 was the most frequent genotype, with mixed infection seen in 26%.( 83 

# ADDITIONAL VACCINES
Note: This guideline does not provide an exhaustive list of vaccines available to PLWH, including travel vaccines or additional vaccines that may be appropriate in specific circumstances. Please see NACI guidelines for further information regarding additional vaccines for PLWH: . canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3vaccination-specific-populations/page-8-immunization-immunocompromised-persons.html#a29

# Measles, Mumps and Rubella (MMR)
Recommendation:
- All PLWH without evidence of immunity and with CD4 cell counts >200 cells/mm 3 should be considered for measles and/or mumps and/or rubella vaccination (given as a two-dose series of MMR vaccine). (B)

# Evidence:
In general, live-virus vaccines should not be used among PLWH. In severely immunocompromised populations, measles can present critically and in a prolonged fashion, with a high risk for severe complications.(92-95) Measles, Mumps, Rubella (MMR) vaccination in PLWH with CD4 cell counts >200 cells/mm 3 appears to be safe with no serious adverse events reported.(96-98) Thus, all PLWH without severe immunosuppression (i.e. with CD4 cell count >200 cells/mm 3 ) and no evidence of immunity to measles, mumps, or rubella should be considered for the MMR vaccine.(29, 99) Evidence of immunity includes being born before 1970 or having previously received two doses of measles-or mumps-containing vaccine. All PLWH born before 1957 or who have previously received one dose of rubella-containing vaccine, have serologic proof of immunity, or have had prior lab confirmed rubella disease, are considered to have immunity against rubella. Thus, serological testing may be indicated to confirm the diagnosis of measles, mumps, or rubella or to determine immune status. Serologic testing is not recommended before or after receiving measles-, mumps-or rubella-containing vaccine. If serology is inadvertently done subsequent to appropriate MMR immunization and does not demonstrate immunity, re-immunization is not necessary.(100)

# Varicella
Recommendation:
- All PLWH without evidence of immunity and with CD4 cell counts >200 cells/mm 3 may be considered for varicella vaccination (given as a two-dose series of varicella vaccine given >3 months apart). (D)

# Evidence:
At the time of publication of these guidelines, there were no published data on varicella vaccination among susceptible PLWH. However, based on expert opinion, varicella vaccine may be safe to offer to susceptible individuals with CD4 counts >200 cells/mm 3 . Live attenuated varicella vaccine remains contraindicated in PLWH with CD4 counts 3 months apart.
A varicella susceptible person is defined as someone who does not have a history of varicella or herpes zoster after 12 months of age and who does not have a history of age-appropriate varicella immunization.
A self-reported history of varicella is adequate for those born before 2004; for those born in 2004 and later, history of a diagnosis by a health care provider is required for reliability. Children who have a history of either physician-diagnosed herpes zoster or lab-confirmed varicella after their first dose of vaccine do not require a second dose. If disease history is uncertain, provide a second dose.( 101)

# Herpes Zoster
Recommendation:
- The use of inactivated herpes zoster vaccine for prevention of shingles in PLWH over age 50 can now be considered. (D) Dosage and schedule: 0.5mL IM at 0 and 2-6 months. No requirement for repeat dosing currently exists. (D)

# Evidence:
Herpes zoster, commonly known as shingles, is a cutaneous manifestation of the reactivation of the varicella zoster virus (VZV), which causes chickenpox. Manifestations increase after age 50 in the general population and include complications such as post-herpetic neuralgia. 

# COVID-19
Recommendation: 

# Evidence:
PLWH aged 18 years or older should be vaccinated for COVID-19 if they have no contraindications (see below). These vaccines are not expected to be associated with more serious or different adverse events among PLWH or other immunocompromised individuals. While the evidence is mixed, PLWH may be at increased risk of serious illness due to COVID-19, and in the absence of contraindications should receive any of the COVID-19 vaccines currently approved in Canada as appropriate for their age group, regardless of CD4 count (i.e.: Pfizer-BioNTech, Moderna, AstraZeneca, and Janssen vaccines).
PLWH who have CD4 counts <200 cells/mm 3 or are not virologically suppressed should be counselled regarding the unknown efficacy and safety of the vaccines given that such subjects were not included in the vaccine licensing studies. For more information, visit the BC-CfE Committee for Drug Evaluation and Therapy (CDET) statement on the use of COVID-19 mRNA vaccines in PLWH: / therapeutic-guidelines/healthcare-providers/therapeutic-guidelines/bc-centre-excellence-hivaids-cdetcommittee-statement.

# CONTRAINDICATED VACCINES
Recommendation:
- The following live vaccines are contraindicated in PLWH: oral polio, live intranasal influenza vaccine, and BCG (Bacillus Calmette-Guerin). (B)

# Evidence:
For PLWH, additional live vaccines (often used in the context of foreign travel) are either contraindicated or should be used with caution in circumstances where the benefits of a live vaccination are likely to outweigh the risks. Primary care providers may wish to consult with a physician with expertise in HIV or immunization about offering such vaccines to PLWH.(106)

# SPECIAL CONSIDERATIONS FOR CISGENDER WOMEN- LIVING WITH HIV (WLWH)
Note: Guidelines and resources specific to pregnancy and post-partum care, and infant care can be found on the Oak Tree Clinic/BC Women's Hospital and Health Centre website: / health-professionals/professional-resources/hiv-aids-resources.

# INTRODUCTION
In Canada in 2018, 29% of newly diagnosed HIV cases were in women,( 1) and among the estimated 63,110 people living with HIV (PLWH) in Canada in 2016, 23 % were women. (2) The majority of women living with HIV (WLWH) acquired the disease via heterosexual contact (64%). This holds true for women born in Canada or other non-endemic countries, as well as immigrants from HIV-endemic countries. Injection drug use is the second most common means of transmission for women (28%).( 3) In BC, the proportion of women affected by HIV is smaller than for the country as a whole: 8% of British Columbians newly diagnosed with HIV in 2017 were women.(4) Similar to national trends, heterosexual contact is the most common route of HIV transmission for women in BC, followed by injection drug use.
Frequently, women are caretakers for children/partners/parents and extended family members/ friends, and they may not give sufficient priority to their own medical/psychosocial care and wellbeing. Furthermore, women frequently face unequal power and socioeconomic relationships with their partners. These social factors may increase women's isolation and depression and compromise their adherence to medical care and their antiretroviral therapy (ART). Continued gender inequities with regard to the social determinants of health, particularly poverty and unstable housing, are significant factors disproportionately impacting women and their ability to participate in HIV care. Women who are Indigenous or from other racialized groups and sex workers are especially vulnerable due to multiple intersecting barriers. WLWH in Canada have very high rates of trauma and post-traumatic stress.(5) Many women are affected by multiple forms of trauma, including adverse childhood events, intergenerational trauma, historical trauma, institutional trauma, and stigma. Refugee women have commonly experienced severe trauma related to armed conflict in their country of origin and sexual assault. Based on data from the Canadian HIV Women's Sexual & Reproductive Health Cohort Study (CHIWOS) study, which included more than 1440 WLWH from three Canadian provinces, more than 79% of WLWH reported experiencing violence in adulthood -four times higher than the prevalence among the general population of women in Canada.(6, 7)
Since trauma is recognized as a root cause of multiple health challenges and is an important social determinant of health, in order to be successful in the care of WLWH, clinicians should address at each HIV visit the social determinants of health, including the person's current personal safety and food and - In this chapter, the term women refers to any persons whose gender identity or expression (i.e. woman) coincides with their sex assigned at birth (i.e. female), also referred to as cisgender women. For a discussion of terms used to describe persons whose gender identity or expression do not coincide with their sex assigned at birth, see the footnote on page 75.
housing security, using a trauma informed care model (/).( 8)
A useful Canadian resource for women-centred HIV care is available at: /.
It should be noted that not all individuals with a cervix or with pregnancy potential self-identify as women, and not all individuals who self-identify as women have a cervix or have childbearing potential.
For this reason, all recommendations are written using gender inclusive language.
It is important for clinicians to provide trauma-informed care and communicate clearly and respectfully with PLWH, to ensure that they receive care that is appropriate to their needs and life circumstances without judgment, assumptions, or unwanted disclosure with respect to their life, gender, and sexuality. This includes respecting the gender identity and expression of individuals (e.g. using their preferred pronoun and name in conversations and in emails and letters from the clinic addressed to the patient), and creating a safe, non-judgmental space for the person to discuss issues related to their sexual, reproductive, and general health. Cultivating this cultural safety for all, including transgender and non-binary individuals, is also an important part of trauma-informed care.

# SPECIAL CONSIDERATIONS RELATED TO ART DURING PREGNANCY AND THE POST-PARTUM PERIOD
Recommendations:
- All pregnant PLWH should be treated with ART for their HIV infection, regardless of their immunologic or virologic status, to prevent infection of their fetus. (A)
- Clinicians should review the latest recommendations regarding ART for individuals who are pregnant or of childbearing potential, since some drugs may be contraindicated or should be used with the guidance of specialized care providers. (D)  

# Evidence:
The indications for and goals of ART are the same for all PLWH. Pregnancy plans and wishes should be discussed with all PLWH in reproductive age potential, in each HIV visit. If pregnancy is desired, preconception counselling should be offered, including education around the importance of attaining maximal and sustained viral suppression before attempting conception and maintaining it throughout pregnancy and delivery, for the health of the pregnant person, to prevent sexual HIV transmission to partners without HIV, and to minimize the risk of HIV transmission to the infant. ART regimen selection preconception and during pregnancy should be made in accordance with current BC Guidelines for the Care of HIV Positive Pregnant Women (), and in consultation with providers who have expertise in this area.
When providing care for individuals planning pregnancy and any individuals of childbearing potential who are not using effective and consistent contraception, providers should carefully review all medications (antiretrovirals  and concomitant medications) and avoid drugs with potential reproductive toxicity. The time of greatest developmental risk to the fetus is the first trimester, often before pregnancy is even recognized.
Like many other chronic conditions (e.g. diabetes), HIV can affect the medical management of pregnancy. Nausea and vomiting during early pregnancy can affect ART adherence. Therefore, pregnancy in PLWH is considered high risk and complex. Consultation with an obstetrician specialising in the management of HIV is recommended. In BC, preconception counselling, ARV regimen guidance, and specialized obstetrical services can be obtained from the Oak Tree Clinic in Vancouver:  or 604-875-2212; a referral form is available on their website ().
Following delivery, clinical, immunologic, and virologic follow-up should continue as recommended for non-pregnant adults and adolescents. ART should be continued post-partum for the optimal health of the individual. Several studies have demonstrated that adherence to ART may worsen in the post-partum period.(9, 10) Clinicians caring for postpartum individuals should specifically address ART adherence, including an evaluation of specific facilitators and barriers to adherence.
Because use of ART during lactation reduces but does not eliminate the risk of transmission of HIV in breast milk, PLWH in BC should be counselled to avoid breastfeeding, where safe alternatives can be provided. (11) In BC, free formula is provided for all babies born to mothers living with HIV for one year, coordinated by the Oak Tree Clinic. PLWH should avoid pre-mastication of food fed to their infants because the practice has been associated with transmission of HIV from parent to child.(12)

# REPRODUCTIVE ISSUES AND GYNECOLOGIC HEALTH IN THE CONTEXT OF HIV
Recommendations:
- Contraception needs and pregnancy plans should be discussed with all individuals of childbearing potential (aged 15-50 years) upon initiation of HIV care and routinely thereafter, as pregnancy may affect the choice and timing of antiretrovirals. (D)
- Selection of a contraceptive method should take into account the PLWH's desires about family planning and preferred contraceptive method, ART regimen, other medications, and co-morbid conditions. (D) Intrauterine devices (IUDs) can be considered as a safe and effective contraception option for PLWH. (B)
- When prescribing ART, clinicians should take into account that some ARVs have significant pharmacokinetic (PK) interactions with hormonal contraceptives; other effective contraception options should be considered to prevent unplanned pregnancy. (B) Switching to an ARV drug that does not have interactions with hormonal contraceptives may also be considered. (B)

# Evidence:
The incidence and prevalence of gynecological problems are high among WLWH throughout the course of their HIV disease.( 13 

# ART AND WEIGHT GAIN IN WOMEN

# Evidence:
Various studies have suggested that sex assigned at birth may influence the frequency, presentation, and severity of some ART-related adverse events, including metabolic complications.(31) Pharmacokinetics of antiretroviral drugs may differ between cisgender men and women, (32) due to factors such as body weight, plasma volume, hormones, gastric emptying time, plasma protein levels, cytochrome P (CYP) 450 activity, drug transporter function, and excretion activity. (33)(34)(35) Several studies indicate that cisgender women experience metabolic complications associated with ART use differently than cisgender men. WLWH are more likely to experience increases in central fat and are at a higher risk of developing particular patterns of lipodystrophy than men living with HIV. Initiation of ART often leads to weight gain. While some of this weight gain may be an appropriate "return-to-health" effect, excessive increases in weight may lead to obesity. Recent data suggest greater weight gain occurs on ART initiation among women than men, especially with the use of integrase strand transfer inhibitors and tenofovir alafenamide (AF). (44)(45)(46)(47) Other factors associated with greater weight gain on ART include black race and lower baseline CD4 cell count. (44,47) The mechanisms by which certain ARV agents differentially contribute to weight gain are unknown and under investigation. In addition to HIV-related effects (CD4 nadir, level of viral load), social/ environmental contributors, and genetic factors on weight gain, there may also be effects of newer, bettertolerated ARV agents, that better target the catabolic effects of HIV.

# MENOPAUSE
Recommendation:
- When systemic menopausal hormone therapy or non-hormonal medications are indicated for PLWH experiencing menopausal symptoms, potential drug interactions with ART should be considered. (B)

# Evidence:
An increasing number of WLWH are living past menopausal age. In Canada in 2018, 22.2% of cisgender women newly diagnosed with HIV were over 50 years of age.(1) Aging with HIV is an emerging field, and it is now expected that newly diagnosed individuals whose HIV is well controlled will have life expectancies similar to the general population.
In Canadian WLWH, the average age for the onset of menopause is 48 years, which is 3 years earlier than women in the general Canadian population. (48) Earlier menopause observed in PLWH may be multifactorial. (49) There are conflicting data on the effect of HIV on menopausal age and symptoms. (50) Factors that can influence menopausal symptoms, including smoking, stress, drug use, depression, low BMI, and race/ethnicity, are also relatively more prevalent among PLWH. Occasionally, symptoms of menopause may be difficult to distinguish from symptoms related to HIV, including fatigue, sleep disturbances, night sweats, achiness, and mental health effects. (50) Sexual practices in menopausal WLWH are not well described. It is important for health care providers to discuss safer sex practices with PLWH of all ages. However, providers need to take into consideration that there are significant power imbalances for many WLWH that may compromise their ability to have safe sex and expose them to potential intimate partner violence.
There are currently no randomized controlled trials delineating the use of menopausal hormone therapy (MHT) in PLWH. As in the general population, MHT can be considered within 5-10 years of starting menopause in PLWH with severe vasomotor symptoms if the individual is below the age of 60.
For those aged 60 years and over, the risk outweighs the benefits, and MHT is not recommended. (51,52) Contraindications for MHT include unexplained vaginal bleeding, severe liver disease, breast or endometrial cancer, congestive heart failure, stroke, dementia, high risk of venous thromboembolism, hypertriglyceridemia, and severe migraine headaches. In individuals with a uterus, the proliferative effects of systemic estrogen on the endometrium must be countered by an appropriate dose of progestogen, to lower risk of cancer, i.e. combination MHT containing two hormones (estrogen and progestogen). For MHT recommendations, see: .
There may be drug interactions of MHT with ART(53, 54) (see / uploads/2019/09/Hormonal-therapy_contraceptives-HRT_Eng.pdf). Levels of estradiol and progestogens may be increased by CYP3A4 inhibitors, especially cobicistat, potentially increasing MHT side effects and long-term thromboembolic risk. Ritonavir-boosted PIs and older non-nucleoside reverse transcriptase inhibitors (NNRTIs, such as efavirenz, etravirine, nevirapine) may change hormone levels, but the role of MHT dose adjustment has not been studied. Consultation with an HIV-experienced pharmacist, HIV gynecologist, or HIV specialist is recommended.
Hot flashes and night sweats related to menopause may also be managed by non-hormonal medications (e.g. venlafaxine, paroxetine, fluoxetine, gabapentin, or clonidine). (51,52) As with MHT, drug interactions with ART should be considered (see DDI Booklet 2019_English.pdf (hivclinic.ca)) and expert guidance sought as necessary. For urogenital symptoms related to menopause, low-dose vaginal estrogen therapy should be considered.( 55) It has limited systemic absorption and therefore has less systemic side effects/ risks, lower interaction potential with ART, and has been shown to improve symptoms.

# BONE HEALTH

# Evidence:
Women have an increased risk of premature bone loss (osteopenia and osteoporosis), particularly during and after menopause, and this risk is exacerbated by HIV and ART. (56,57) The prevalence of osteoporosis in WLWH is three times greater compared with HIV-uninfected women in the same age group in the United States.( 58)
The pathogenesis of reduced bone mineral density (BMD) noted in PLWH is multi-factorial, with increased risk associated with some 

# SPECIAL CONSIDERATIONS FOR TRANSGENDER  INDIVIDUALS LIVING WITH HIV
Recommendations:
- Endocrine therapy for transgender individuals living with HIV should be provided in consultation with an endocrinologist or other clinician who has experience providing endocrine care to transgender individuals. (D) 

# Evidence:
Transgender populations are disproportionately affected by HIV. In a systematic review and meta-analysis among the United States (US) transgender population between 2006 and 2017, the estimated prevalence of HIV infection overall was 9.2% (compared to 13.3 per 100,000 in the US general population in 2018) and was higher among transgender women (14.1%, vs. 4.8 per 100,000) than transgender men (3.2%, vs. 22.1 per 100,000).(1, 2) Numerous challenges can affect health outcomes for transgender people, including socioeconomic factors, mental health issues, substance use, abuse and trauma, stigma, discrimination, social rejection, and exclusion. (3,4) Lack of knowledge of transgender issues among health care providers and prior negative experiences in the health care system may constitute barriers to the transgender person's ability to access and maintain HIV care. Providers should be aware that transgender people may prioritize other health concerns over HIV (e.g. gender-affirming and non-discriminatory care, hormone therapy and its side effects, mental health care including trauma recovery), potentially leading to challenges with adherence to antiretroviral therapy (ART). (4,5) In BC, the care of transgender individuals is provided through a decentralized community-based model of care. While HIV treatment and gender-affirming endocrine therapy may be administered by different providers, transgender people living with HIV (PLWH) should have access to all facets of health care in a safe, welcoming, and respectful clinic environment. For information on the care of transgender individuals, clinicians can refer to Gender-affirming Care for Trans, Two-spirit, and Gender Diverse Patients in BC: A Primary Care Toolkit (September 2019) (/ Note: In this document, transgender includes any person whose gender identity or expression is different from their sex assigned at birth. Transfeminine is used to mean people who were assigned male sex at birth and transmasculine is used to mean people who were assigned female sex at birth and both have gender identity or expression that do not align with their sex assigned at birth.
HealthProf/Primary-Care-Toolkit.pdf). Additional resources for primary care providers are available at: .
Gender-affirming endocrine therapy, which allows the acquisition of secondary sex characteristics aligned with the individual's gender identity, should be provided in consultation with an endocrinologist or other clinician who has experience and expertise in this area. The general approach of feminizing hormone therapy is to combine an estrogen (transdermal, injectable , or oral 17-beta estradiol) with an androgen antagonist (spironolactone, cyproterone acetate, bicalutamide, dutasteride), and in some cases a progestin (micronized progesterone or medroxyprogesterone).( 6) Masculinizing hormone therapy involves the use of one of several forms of testosterone (e.g. injected, transdermal patch or gel, intranasal).( 6) There is considerable variation in the medications that are used for gender affirmation depending on provider and patient preference.
Estradiol, cyproterone, bicalutamide, dutasteride, progestins, and testosterone are substrates of CYP3A4 and may have clinically significant drug interactions with certain ARVs. (7,8) No significant drug interactions are expected between ARVs and spironolactone or finasteride. Estradiol levels may be increased with concomitant cobicistat, increased or decreased with ritonavir, and decreased with efavirenz, etravirine, or nevirapine. Levels of cyproterone, bicalutamide, dutasteride, progestins, and testosterone may be increased with concomitant cobicistat or ritonavir, and decreased with concomitant efavirenz, etravirine, or nevirapine. In transgender individuals receiving endocrine therapy, ART should be chosen to include a non-interacting agent such as doravirine, rilpivirine, or an unboosted integrase inhibitor (raltegravir, dolutegravir, or bictegravir). Otherwise, hormone efficacy and toxicity should be monitored and the hormone doses should be adjusted as necessary.( 7)
BC Cancer provides guidance for healthcare professionals regarding breast/chest screening for transgender, gender diverse, and non-binary people (). Transmasculine individuals who have not had bilateral mastectomy and transfeminine individuals between the ages of 40 and 74 who have taken estrogen-based hormone therapy for more than 5 years should be screened according to the BC Cancer breast screening policy for cisgender (non-transgender) persons (/ breast/eligibility). Transfeminine individuals who have never taken estrogen-based hormone therapy or have taken hormones for fewer than five years do not need to be screened regularly for breast cancer.
For information regarding cervical cancer screening for transgender PLWH with a cervix, see Section 7.10, page 93, of this document. For further guidelines on cervical cancer screening among transgender individuals, see the BC Cancer website:  GuidelinesManual-ScreeningForCancerOfTheCervix.pdf.
For Trans Care BC recommendations regarding sexual health screening and pelvic examinations, see:  .

# COMMON NON-INFEC TIOUS CO-MORBIDITIES 7.1 INTRODUCTION
A number of conditions not traditionally associated with AIDS, including cardiovascular and renal disease, are exacerbated in the presence of uncontrolled HIV replication.(1) Therefore, despite the potential for long-term complications due to chronic antiretroviral therapy (ART), the benefits outweigh the potential risks in people living with HIV (PLWH) who are appropriately treated and monitored.(2) To this end, clinical and laboratory assessment of relevant co-morbid conditions should be performed at baseline before initiation of ART and during follow-up. Screening for non-infectious comorbid conditions is described in Appendix 3, page 114.
The frequency of lab monitoring for antiretroviral toxicity depends on the known potential toxicities of specific drugs, concomitant medications, and underlying co-morbid conditions. Lab monitoring may occur every 4 weeks after initiation of therapy, decreasing to up to every 6 months after stabilization of the patient on their antiretroviral (ARV) regimen.(3) In most cases, the timing of safety laboratory monitoring can be coordinated with monitoring of HIV RNA and CD4 cell counts. For details regarding laboratory monitoring for individuals receiving ART, see Chapter 3 of the BC-CfE Guidelines for Antiretroviral ARV Treatment of Adult HIV Infection | (bccfe.ca).

# CARDIOVASCULAR DISEASE

# Recommendations:
- All PLWH should be screened for risk of cardiovascular disease at least annually, and modifiable cardiovascular risk factors should be addressed where possible. (D)
- Blood pressure should be measured at least annually and at each visit (at least every 6 months) if abnormal. (D)
- Assess lipids (total, HDL, and LDL cholesterol, and triglycerides) and/or apolipoprotein B at baseline and every 6-12 months once patient begins antiretroviral therapy. (B)
- An electrocardiogram (ECG) should be considered at baseline and periodically (at intervals determined by the degree of risk) in patients taking protease inhibitors and/or rilpivirine with other PR-or QTc-prolonging drugs. (D)

# Evidence:
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the general population.
HIV infection is associated with a doubling of the risk of CVD, including acute myocardial infarction (MI), stroke, peripheral arterial disease, heart failure, and sudden cardiac death.(4-6) Globally, the burden of HIV-associated CVD has tripled over the last 20 years.( 4)
The mechanisms underlying the increased CVD risk in PLWH include a preponderance of traditional risk factors in this population, including smoking, hypertension, dyslipidemia, diabetes, and metabolic syndrome. (4,5) In addition, uncontrolled HIV infection, including during ART interruption, is associated with chronic inflammation and an increased risk of cardiovascular events. (1,7) Even in the setting of controlled HIV viremia, underlying chronic vascular inflammation directly contributes to accelerated atherosclerosis and endothelial dysfunction. Elevated levels of some inflammatory biomarkers, notably high-sensitivity C-reactive protein (hsCRP), are independently associated with a higher risk of MI in PLWH, as in the general population. (8,9) However, the interpretation of hsCRP and other inflammatory biomarkers can be complicated in the setting of the chronic inflammatory state associated with HIV infection. Although ART reduces the levels of these biomarkers, they can remain elevated compared with those of HIV-negative individuals. The clinical utility of these biomarkers for initiation or monitoring therapy in PLWH is unknown.
While virally suppressive ART reduces risk of clinical CVD events,(1) specific ARV agents can be associated with increased CVD risk. In the D:A:D observational cohort from 1999 to 2005, the rate of CV events increased by 16% per year of exposure to ART regimens including older protease inhibitors (PIs). (10) However, more recently, the rate of MI in PLWH has plateaued, attributable at least in part to the use of contemporary PIs; in the D:A:D study from 2009 to 2016, use of darunavir/ritonavir was associated with an increase in CVD risk (59% per 5 years additional use), while use of atazanavir/ritonavir was not.
(11) Although rates of MI are declining in recent years, PLWH receiving newer ART regimens remain at an increased risk of other forms of CVD, notably atrial fibrillation and heart failure. (5) The association between recent use of abacavir and acute MI remains controversial, but most current guidelines recommend avoidance of this agent in people with established CVD or who are at a high risk for CVD.
(5, 12) Some ARV agents such as efavirenz may contribute to CVD risk through their detrimental effect on serum lipids (especially triglycerides and LDL cholesterol), while other have beneficial effects on lipid profiles, including tenofovir DF (compared to tenofovir AF) and unboosted integrase inhibitors. (13)(14)(15)(16) The Canadian Cardiovascular Society Guidelines () recognizes HIV as a significant risk factor for premature CVD and an indication for screening for cardiovascular risk factors, including lipids, regardless of age.(17) Screening for lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) and apolipoprotein B (apoB) can be done non-fasting, except in individuals with a history of triglycerides >4.5 mmol/L, where these tests should be performed in a fasting state. ApoB measurement is subject to less laboratory error than LDL cholesterol, particularly in patients with hypertriglyceridemia (as often seen in HIV). LDL cholesterol is currently recommended as the primary treatment target, but apoB and/or non-HDL cholesterol are alternatives and may be the preferred treatment targets in the future. (17) Lipids and apoB should be measured annually, and monitoring frequency should be increased to every 6 months if abnormalities are detected.
Despite the impact of ART and HIV infection itself, traditional CVD risk factors (including age and smoking) remain the most important contributors to CVD in PLWH. (17,18) A modified Framingham Risk Score (FRS) (), where the 10-year FRS percentage is doubled for a family history of premature CVD, is the recommended tool for assessing total 10-year CVD risk in the general population; (17) 21) a switch to a more lipid-friendly ART regimen may also be a consideration.(5) When needed, statins can be used safely for the treatment of dyslipidemia in HIV,( 22) but potentially significant drug-drug interactions between lipid-lowering agents and antiretrovirals (e.g. statins and PIs) must be taken into account (www.hiv-druginteractions.org) (DDI Booklet 2019_ENG DIGITAL.pdf (hivclinic.ca)). Of note, PLWH may not reach desirable lipid targets with conventional statin therapy and combination therapy may be necessary. (23,24) Some older HIV PIs (specifically saquinavir and lopinavir/ritonavir) were associated with PR interval prolongation or QTc interval prolongation. (25)(26)(27) Case reports have also described QTc prolongation and torsades de pointes in association with atazanavir(28) and efavirenz.(29) Cardiac conduction abnormalities may become clinically significant when a ritonavir-boosted PI is co-administered with one or more QTc-prolonging drugs such as methadone, quetiapine, macrolides, quinolones, and/or azoles (for a full list, see the CredibleMeds website at ), or PR-prolonging drugs, such as digitalis, calcium channel blockers, anti-arrhythmics, and beta-blockers. Rilpivirine was associated with QTc prolongation at daily doses of 75 mg or 150 mg, although this does not appear to be a problem at the 25 mg daily dose currently in use. (30)(31)(32) An electrocardiogram (ECG) should be considered at baseline before starting a ritonavir-boosted PI and/or rilpivirine with one or more PR-or QTc-prolonging drugs. A repeat ECG should be performed approximately five half-lives after starting the relevant drug, i.e. approximately 2 days after starting atazanavir/ritonavir, 3 days after starting darunavir/ ritonavir, or 10 days after starting rilpivirine. In addition, an ECG should be done after the addition or dose increase of any other QTc-prolonging drug and at times of increased risk (e.g. hypokalemia, hypomagnesemia). Repeat ECG monitoring should be performed at intervals determined by the degree of risk, i.e. whether the QTc is short (0.45 seconds).(33)

# INSULIN RESISTANCE (IR) AND DIABETES MELLITUS (DM)
Recommendations:
- Fasting blood glucose (FBG) and/or glycated hemoglobin (HbA1C) should be performed in all PLWH at baseline and at 6-to 12-month intervals during antiretroviral therapy. Abnormalities in fasting glucose and/or HbA1C should be evaluated and managed according to the Diabetes Canada guidelines (/). (A)
- Initial management of blood glucose abnormalities in PLWH involves lifestyle changes (weight loss, diet, exercise). (A)
- Oral anti-glycemic agents and injectable anti-glycemic agents should be used as required, keeping in mind drug interactions with some antiretrovirals. (A)
Evidence:
HIV and its treatment increase the risk of insulin resistance (IR) and diabetes mellitus (DM) by approximately 1.5-to 4-fold compared to the general population, (34,35) and the risk is greater with hepatitis C co-infection.(36) IR is associated with use of older nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs).( 37) Integrase inhibitors may be associated with weight gain, which in turn exacerbates the risk of diabetes, particularly in PLWH; however, an association between integrase inhibitors and clinical metabolic abnormalities has yet to be confirmed. (38,39) Traditional risk factors for DM remain relevant in PLWH.
HbA1C may be monitored as an alternative to fasting blood glucose, particularly if fasting status is difficult to ascertain; however, HbA1C can underestimate glycemia in PLWH, leading to under-diagnosis, especially in the setting of macrocytosis, lower CD4 cell counts, or certain antiretrovirals. (40)(41)(42) Fasting glucose and HbA1C should be measured annually in PLWH, with frequency of monitoring increased to every 6 months if abnormalities are detected.
In PLWH with type 2 diabetes, HbA1C should be measured every 3 months and targets should be established as per the Diabetes Canada Guidelines.(43) HbA1C targets are individualized; in most cases the target is 7%. In type 2 diabetics with CD495 fL, glucose levels should be used instead of HbA1C to guide management.
As in the general population, initial management of blood glucose abnormalities in PLWH involves lifestyle changes: maintaining healthy weight, healthy diet, and physical activity.(44) Depending on the degree of hyperglycemia at diagnosis, antihyperglycemic agents should be started concomitantly or if blood sugar targets are not met within 3 months of instituting healthy behaviour interventions.(45) Of note, in the presence of dolutegravir, metformin concentrations are increased by 79%, with a potential for increased adverse events. (46) In patients taking dolutegravir, metformin should be started at a low dose and not prescribed in doses greater than 1000 mg daily. Bictegravir increases metformin levels by 39% and no dose adjustment is required for co-administration.(47) In individuals with established cardiovascular disease with suboptimal glycemic control there is a clear role for sodium-glucose cotransporter-2 (SGLT-2) inhibitors and/or glucagon-like peptide-1 (GLP-1) receptor agonists;(45) some precautions should be noted with respect to potential drug interactions with antiretrovirals (TS_Antidiabetic_2019_Oct.pdf (liverpool-hiv-hep.s3.amazonaws.com); DDI Booklet 2019_English.pdf (hivclinic.ca).

# BONE
Recommendations:
- Clinicians should undertake preventive measures for bone loss in all PLWH, including weightbearing exercises, maintaining ideal weight, reducing smoking and alcohol consumption, and optimizing vitamin D (1000-2000 IU/day) and calcium intake (in the form of diet and/or supplements if necessary). (D) 

# Evidence:
PLWH are at a greater risk of fractures than non-infected individuals. (48) The loss of bone density associated with normal aging is accelerated by HIV-associated chronic inflammation and vitamin D deficiency and by exposure to antiretrovirals. (49) The role of specific antiretrovirals in causing bone loss is controversial; however, the evidence points to tenofovir DF and ritonavir-boosted PIs as the leading culprits. (49,50) Efavirenz has also been implicated as a contributor to low bone mass, mediated through its effect on vitamin D metabolism.( 51 Preventive measures for bone loss should be implemented in all PLWH, regardless of age, following the recommendations for the general population (/). These measures include regular weight-bearing exercises, maintaining ideal weight, reducing smoking and alcohol consumption, and optimizing vitamin D and calcium intake (in the form of diet and supplements if necessary). Falls prevention strategies should be implemented for individuals with frailty or other conditions associated with a high risk of falling (https:// www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/osteoporosis). Most PLWH have low vitamin D levels, as does the general North American population; therefore, there is insufficient evidence to support routine measurement of vitamin D levels in PLWH. (58) While there is no consensus regarding the optimal dose in the setting of HIV, supplementation with vitamin D at doses of 1000-2000 international units (IU) daily is inexpensive, safe, and not associated with known interactions with antiretroviral drugs. If dietary calcium intake is inadequate, a calcium supplement should be considered, taking into consideration potential interactions with antiretrovirals.

# RENAL DISEASE

# Recommendations:
- It is recommended that laboratory assessment of renal function (i.e. serum creatinine, estimated glomerular filtration rate , serum phosphate, urinalysis for protein and sediment, and spot urine for albumin to creatinine ratio ) should be performed in all PLWH at baseline and every 3-4 months after starting antiretrovirals, increasing to 6-month intervals when stable (depending on degree of risk). (D)
- Blood pressure should be measured at least annually and at each visit (at least every 6 months) if abnormal. (D) - Rarely, acute interstitial nephropathy with reversible acute renal failure, which has been described in association with hypersensitivity reactions to abacavir, efavirenz, and atazanavir (67) Establishing the etiology of renal dysfunction in PLWH can be difficult as it is often multi-factorial.
Referral to a nephrologist and possibly renal biopsy may be required for a definitive diagnosis, especially in cases where drug-related nephrotoxicity is suspected. Any renal function abnormalities identified at screening should be investigated and managed appropriately as in the general population. Some ARVs (specifically all NRTIs except abacavir) are renally cleared and may require dosage adjustment if renal function is abnormal.(59) For some drugs with low nephrotoxic potential (e.g. lamivudine), the beneficial effect of dose adjustment has not been proven. However, tenofovir DF is renally cleared and is also a nephrotoxin; this drug should be avoided in patients with renal disease or at high risk. If renal dysfunction occurs during ART, tenofovir DF should be discontinued if possible and replaced with another agent (e.g. abacavir if HLA-B*5701 negative or tenofovir alafenamide  if eGFR >30 mL/min) rather than dose-reduced. For further information, refer to the BC-CfE Guidelines for Antiretroviral ARV Treatment of Adult HIV Infection | (bccfe.ca).
Certain ARV agents (bictegravir, dolutegravir, rilpivirine) and pharmacokinetic enhancers (cobicistat) affect renal tubular creatinine transporters resulting in decreased tubular creatinine secretion and increased serum creatinine levels. (31,32,(68)(69)(70)(71)(72)(73)(74) This is manifested as a factitious increase in serum creatinine (mean increase ~10-12 mol/L) during the initial 2-8 weeks of therapy, without an effect on true glomerular filtration rate. After the initial increase, serum creatinine levels remain stable at the new higher level as long as the agent is continued. Decreases in eGFR that are >25% of the baseline level, that start later or continue to progress after the first 2-8 weeks of therapy, or that are accompanied by signs of renal tubular dysfunction (e.g. proteinuria) require further investigation to rule out true renal function impairment, and nephrology referral should be considered.(74)

# HYPOGONADISM
Recommendations:
- Cisgender men living with HIV presenting with symptoms of hypogonadism should be assessed with a morning serum total testosterone level; an abnormal testosterone level should be confirmed with repeat testing. (B) An estimated bioavailable testosterone measurement may be helpful to assess certain individuals, including obese cisgender men with borderline low total testosterone levels. (B)
- Testosterone replacement is indicated only for symptomatic cisgender men with total testosterone levels less than 10 mmol/L (B) and should be prescribed in consultation with a specialist. (D)
- Endocrine therapy for transgender individuals living with HIV should be provided in consultation with an endocrinologist or other clinician who has experience providing endocrine care to transgender individuals. (D)

# Evidence:
In the early ART era, hypogonadism was identified as an important contributor to loss of lean body and muscle mass, the hallmarks of AIDS-associated wasting, as well as decreased bone mineral density.(71) While less prevalent now, low testosterone levels are still present in a significant minority of cisgender men living with HIV. (75) Symptoms suggestive of testosterone deficiency include decreased libido, erectile dysfunction, hot flashes and sweats, weight loss, reduced muscle strength or exercise capacity, fragility fractures, sleep disturbance, fatigue, and depression. Cisgender men living with HIV presenting with one or more of these symptoms should be screened with a morning free testosterone level, and low levels should be confirmed on repeat testing.(76) An estimated bioavailable testosterone measurement may be helpful to assess certain individuals, specifically obese cisgender men with borderline low total testosterone levels. Normal serum testosterone levels in cisgender women are unknown.
Confirmed low testosterone levels may necessitate further investigation (including luteinizing hormone, follicle-stimulating hormone, prolactin, prostate-specific antigen) to distinguish primary (testicular) vs. secondary (pituitary/hypothalamic) hypogonadism and to rule out other clinical conditions.(77) Testosterone replacement therapy (TRT) is indicated only for cisgender men with symptomatic low testosterone levels and should be prescribed according to current guidelines, preferably in consultation with an endocrinologist or other specialist. (76,78) In cisgender men living with HIV with hypogonadism, TRT has been shown to improve mood, energy, libido, muscle strength, and body composition (specifically, decreasing fat and increasing muscle mass), without adverse effects on viral load or CD4 cell count. However, there are no reliable data demonstrating that TRT improves muscle mass, in excess of that achieved by physical exercise, or overall physical function in cisgender men living with HIV. The benefits of longer term TRT (>3-6 months) in this population have not been studied. (76) Potential side effects of TRT include acne, male pattern balding, and sleep apnea. More serious potential adverse effects include myocardial infarction (due to erythrocytosis) and prostate cancer. TRT is contraindicated in men with acute coronary syndrome or prostate cancer. The long-term safety of TRT is unknown; the need for ongoing TRT should be reassessed at least every 6 months.(76, 78)

# NEUROCOGNITIVE IMPAIRMENT
Recommendations:
- ART to suppress plasma viral load should be started early and administered continuously to prevent or minimize HIV-related neurocognitive impairment. (B)
- In PLWH presenting with cognitive complaints that affect their daily functioning, an investigation should be done to rule out relevant underlying conditions. (B)

# Evidence:
HIV can affect the central nervous system (CNS), impacting cognitive function (e.g. memory, reasoning, planning, solving problems, attention, concentration) and activities of daily living. Fortunately, the incidence of severe cognitive impairment in the form of HIV-associated dementia has declined significantly since the advent of ART. However, milder forms of neurocognitive impairment remain prevalent, even in the presence of virologic suppression, and can have a significant impact on quality of life and adherence to HIV medications. (79) PLWH with impairment in two or more cognitive domains and mild to moderate impairment in daily functioning, in the absence of confounding conditions, may be diagnosed with mild neurocognitive disorder.(80) Potential underlying conditions that need to be ruled out include:(81, 82) In the absence of relevant underlying conditions, neurocognitive impairment in HIV may be related to CSF viral "escape", i.e. presence of detectable HIV RNA in CSF despite undetectable viral load in plasma.
Limited evidence exists that adjusting the ART regimen to include agents with better CSF penetration (e.g. zidovudine, nevirapine, abacavir, emtricitabine, darunavir/ritonavir, raltegravir) can stabilize or improve neurocognitive function in this setting. (79,82) Referral to a physician with expertise in the management of HIV is advised in these situations. Full suppression of plasma viral replication remains the most important target, for both prevention and treatment of HIV-related cognitive disorders.

# LUNG DISEASE

# Recommendations:
- Smoking cessation should be strongly encouraged in all PLWH because they are at a higher risk for chronic obstructive pulmonary disease (COPD) and lung cancer than smokers who do not have HIV. (A)
- A chest X-ray should be performed at baseline in all PLWH. (D) Once infection has been treated or ruled out, patients with persistently abnormal chest X-ray findings should be investigated and referred to a respiratory specialist if necessary. (D) 

# Evidence:
Compared to the general population, PLWH have a greater risk for chronic obstructive pulmonary disease (COPD) and are prone to develop it at a younger age, even taking into account the relatively high rates of smoking in this population. (83,84) COPD should be managed according to current Canadian Thoracic Society guidelines (available at /), including an aggressive plan for smoking cessation. The use of all inhaled steroids should be avoided if possible in patients receiving ritonavir or cobicistat as part of their ART regimen, due to the risk of adrenal suppression and iatrogenic Cushing's syndrome. (85,86) Beclomethasone cannot be recommended as a "safer" alternative in this setting; a systematic review showed this agent has no clinical effect in COPD. (87) If combination inhaled steroids/long-acting beta-agonist (LABA) inhalers are necessary for the management of severe COPD symptoms, consideration should be given to switching patients off of ARV regimens containing ritonavir or cobicistat. Salmeterol is not recommended with concomitant ritonavir or cobicistat in PLWH with COPD because of elevated salmeterol levels that may increase the risk of cardiovascular adverse events. (88) Formoterol can be associated with QT prolongation and should be used with caution in patients receiving QT-prolonging ARVs (rilpivirine, ritonavir-boosted lopinavir or atazanavir); however, other single-agent LABAs (e.g. indacaterol) and long-acting muscarinic antagonists (LAMAs, e.g. aclidinium, glycopyrronium, tiotropium) can be used safely in this setting.(88)
A chest X-ray should be performed at baseline in all PLWH. As HIV confers an increased risk of lung cancer, HIV care providers should have a low threshold for performing chest CT in the presence of significant respiratory symptoms, particularly in smokers. (89)(90)(91) After appropriate management of infectious etiologies, consultation with a respiratory specialist is advisable to investigate persistent symptoms or abnormal imaging findings.

# LIVER DISEASE/CIRRHOSIS
Recommendations:
- Liver enzymes and liver function should be assessed in all PLWH at baseline and every 3-4 months after starting ART, increasing to 6-month intervals when stable. (D) 

# CANCER
Recommendations:
- In PLWH, screening for breast, colorectal, and prostate cancer should follow current provincial recommendations for the general population. (A) 

# Evidence:
The incidence of AIDS-defining cancers, Kaposi's sarcoma, and non-Hodgkin's lymphoma has markedly decreased in the highly active ART era (with the exception of invasive cervical cancer which has remained relatively unchanged), while non-AIDS-defining cancers have become more common. (106)(107)(108) This is attributable at least in part to the increasing risk of malignancy as the PLWH population ages.  1. Mental health should be proactively assessed during clinic visits, and identified conditions should be managed using a stepped-care approach. (D)

# Evidence:
The populations at risk of HIV acquisition are also at heightened risk of anxiety, depression, and other mental health issues, including people who inject drugs (118) and cis-and transgender men who have sex with men (MSM). (119)(120)(121) Sexual minorities and transgender individuals carry a disproportionate burden of mental health challenges as indicated by higher rates of self-reported depression, anxiety, selfharm, suicidality, and substance use disorders when compared to their heterosexual counterparts. (119)(120)(121)(122) In this sense the intersecting burdens of mental illness, substance use disorders, and experiences of discrimination related to sexuality among these populations impart an increased vulnerability towards HIV acquisition.( 123)
Cisgender women living with HIV also experience high rates of anxiety, depression, and post-traumatic stress disorder (PTSD).( 124 

# SPECIAL CONSIDERATIONS FOR INDIVIDUALS WITH ADVANCED HIV -OPPORTUNISTIC INFEC TION & PROPHYLAXIS
Despite efforts to expand HIV testing and the accessibility of effective antiretroviral therapy (ART) in British Columbia, just under 20% of people living with HIV (PLWH) are diagnosed at an advanced stage of HIV disease.(1) Others may not access medical care including ART or are unable to adhere to their ART regimen consistently. Such individuals may develop low CD4 cell counts, which places them at risk for opportunistic infections (OIs), and indeed an OI is often the presenting feature that brings them into medical care. Once the acute OI has been treated, primary prophylaxis for other common OIs may be appropriate if the CD4 cell count remains low. Following immune reconstitution with ART, primary prophylaxis can often be discontinued once the patient is clinically stable and has established consistent adherence. Indications for prophylaxis, agents of choice, and criteria for discontinuing and restarting primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP), Toxoplasma, Mycoplasma (M.) tuberculosis, and Mycobacterium avium complex (MAC) are shown in  

# HEALTH SERVICES TO OPTIMALLY ENGAGE PEOPLE LIVING WITH HIV (PLWH) IN EFFEC TIVE PRIMARY CARE
Chapter Summary:
- Optimal HIV management is facilitated by healthcare delivery models that are focused on long-term engagement and relationship-building between healthcare providers and their clients.
- Actively linking individuals newly diagnosed with HIV to clinicians who are familiar with the HIV management is preferred to passive referrals or simply providing patients information. In BC, regional public health nursing teams may be helpful in linking newly diagnosed individuals to care.
- Peer support or peer-navigation may also be helpful for linking or retaining some PLWH in care 4. Formal case management to link and/or retain PLWH in care may be needed for some individuals.
- PLWH may face additional challenges such as housing instability and food insecurity, which should be addressed through referrals to specific social services.
- Outreach support, such as those provided by public health nursing teams though health authorities, are a helpful resource in assisting PLWH to remain engaged in care.
Engaging people living with HIV (PLWH) in healthcare and ensuring client retention are key elements to providing successful treatment, ensuring adherence to antiretroviral treatments, and preventing onward disease transmission.(1, 2) However, PLWH may encounter a variety of challenges to accessing consistent and effective care. Some factors are patient-dependent, such as negative emotions associated with diagnosis(1) and a lack of adequate social supports. (1,2) Other factors are associated with health services themselves, such as negative healthcare experiences(1) and lack of culturally sensitive care for Indigenous people and other cultural minorities.(3)
Healthcare providers and staff who are perceived to be supportive and collaborative are important to establishing rapport with PLWH, and these positive relationships can, in turn, improve linkage to healthcare. (1,4,5) Moreover, supportive providers may be seen by patients as members of their supportive social network and as proxies for absent friends and family.(1) In addition, providing appropriate education around HIV, through programmes tailored for PLWH or by care providers trained/competent in providing patient education, improves patient empowerment and understanding of antiretroviral therapy (ART).(6, 7) Patients also highly value confidentiality as the fear of incidental disclosure when seeking services is a concern for many PLWH accessing care.(7) Client-centred healthcare that accounts for patient preferences and is culturally sensitive and confidential underpins the effective delivery of HIV services. (3,5,8,9) In BC, all residents are eligible for care and treatment of HIV free of charge. Care providers who are faced with challenges of caring for visitors without health insurance and/or persons residing in Canada illegally should contact the BC-CfE to advocate on the person's behalf for coverage of the cost of medical treatment.

# CHRONIC DISEASE MODEL OF CARE
As HIV is now conceptualized as a chronic, manageable condition, its optimal management is facilitated by care models that are focused on long-term engagement and relationship-building between healthcare providers and their clients. The Chronic Care Model, first formulated by Wagner et. al. in 1996(10) and recently revisited,(11) addresses relational aspects of care (Figure 9.1). At its core, the Chronic Care Model postulates that an informed and activated client, when partnered with a proactive and prepared healthcare team, will achieve optimal outcomes for chronic disease management. HIV care has been evaluated in terms of how well it incorporates aspects of the Chronic Care Model;(12-14) however, we are not aware of studies which have evaluated different service delivery models in terms of clinical outcomes. Many aspects of care related to the Chronic Care Model have recently been identified as priorities for PLWH in high-income countries.(7) These include: a strong healthcare professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and patient involvement in decisions about treatment and care. Other studies have shown that better physician-patient relationships are associated with higher rate of adherence to ART. (15) Quality improvement involves routine data collection and cycles of planning, change, and feedback to improve processes and outcomes. Incorporating quality improvement methods in HIV care can provide useful feedback throughout cycles of change, including the implementation of an intervention, and help close gaps in care.( 16) For more information on best practices for quality improvement and evaluation of HIV care and services, please consult the resources available on the HIV Continuum of Care Collaborative website (/).

# ACTIVE REFERRAL FOLLOWING DIAGNOSIS
Upon diagnosis, active guidance to set up initial clinic appointments rather than passive methods (e.g. handing out brochures) improves linkage,(1) as does scheduling clinic orientation visits. (17) In BC, regional public health teams may be helpful in linking newly diagnosed individuals to clinicians who are familiar with the management of HIV infection. A list of contact numbers can be found in the Appendix 4, page 116. As well, The Canadian AIDS Treatment and Information Exchange (, 1-800-263-1638) is a national organization that provides useful support and information regarding HIV treatment and related topics in languages accessible to most clients. 

# ADDRESSING SOCIAL DETERMINANTS OF HEALTH
PLWH may face additional challenges such as housing instability and food insecurity. Stable housing among PLWH has been associated with a variety of positive clinical outcomes, including adherence to ART and improvement in overall health status, (18,19) As well, evidence from randomized trials has demonstrated that receiving assistance or other services that improve housing status has a direct impact on improved medical care and health outcomes for formerly homeless or inadequately housed PLWH. (20,21) Food insecurity has been associated with a lack of virologic suppression among PLWH receiving ART, with 37% of those with unsuppressed viral load reporting food insecurity; (22) food insecurity has also been associated with increased mortality among PLWH who use injection drugs in studies conducted in BC( 23) and New York. (22) Clinicians should actively ask PLWH about these issues and have connections to social work supports and community organizations so that they can actively assist patients in accessing appropriate programs and services.

# PEER-SUPPORT AND PATIENT OR PEER NAVIGATION
Stigma, isolation, and marginalization are common realities in the lives of PLWH. Ensuring access to social and emotional support for affected individuals is a crucial part of HIV primary care. Peer support programs can help to improve linkages and retention in care. AIDS service organizations (ASOs) are excellent starting points for many of these services. Please refer to the Contact List (Appendix 4, page 117 for a list of provincial organizations, providing support for PLWH).
Patient navigators, who may be peers with lived experience, assist in relationship-building and nonmedical support. Peer navigators may accompany clients to appointments, guide clients through the healthcare system, teach skills in communicating with providers, and provide non-clinical services such as transportation. (17,24) Peers may also provide basic information on HIV medications and support treatment adherence, including reinforcing messages regarding treatment as prevention or U=U. Peers can also provide education regarding sexually transmitted infections and other related topics. Moreover, peers can connect patients with community organizations and provide referrals to services and support groups, including addiction and mental health support. Patient and peer navigators have been found to improve linkage to and retention in healthcare by supporting clients in navigating complex medical systems to meet their care needs. (24,25) Guidelines for peer navigation services have been published by the Canadian AIDS Treatment Information Exchange. (26) In BC, several community-based organizations provide peer navigation or peer support services, including Vancouver Island PWA Society (. com/programs/peer-support/) and AIDS Vancouver (). Health care providers should contact their regional health authority's HIV program if they have clients who could benefit from peer navigation or support.

# CASE MANAGEMENT
Case management has been shown to be effective in both initial linkage to care (27) and subsequent retention in care (28,29) and often comprises a variety of interventions. Case management may consist of assistance from a healthcare worker to link PLWH to HIV care providers with time-limited follow-up to ensure that linkage and retention have occurred. Case management may also include referring clients to appropriate providers, assisting clients to prioritize personal needs, introducing HIV resources, helping to complete forms, and teaching skills about disclosure to support networks.(17) Case management activities may overlap with patient/peer navigation.(24)

# OUTREACH SERVICES
Intensive outreach services (e.g. home visits or mobile van outreach) were also found to increase retention and ART adherence, though the programs could be resource-intensive and lack long-term stability. (6,17) Outreach services can be provided by medical professionals or by peers. These programs may work better when integrated with other social services. (6) In BC, all regional health authorities have outreach nursing teams to assist PLWH who have not engaged in HIV care following diagnosis or who have fallen out of care. At Vancouver Coastal Health, these outreach personnel are known as STOP teams; they have different names in other regional health authorities. Contact information for these teams are found in Appendix 4, page 117.
The Re-Engagement and Engagement in Treatment for Antiretroviral Interrupted and Naive populations (RETAIN) Initiative () is a partnership between the BC-CfE, Medical Health Officers from each health authority, and HIV outreach personnel throughout British Columbia. The BC-CfE sends routine alerts to physicians regarding their patients who are at least 2 months late in refilling their ART prescription. Additionally, alerts have been launched for physicians linked to patients newly diagnosed with HIV who have not yet accessed ART. Both of these alerts include contact information for local public health support.
A core component of RETAIN is the routine province-wide coordination of public health support for PLWH who have interrupted ART or who have yet to initiate therapy. PLWH will be eligible for this outreach support if: 1) they have interrupted treatment for longer than 4 months, or 2) they have not yet started treatment more than 4 months after a high plasma viral load was reported. The BC-CfE provides routine referrals for such clients to each regional health authority on a monthly basis. An evaluation of the RETAIN program demonstrated that, among individuals who had interrupted treatment for >4 months, those who interrupted their treatment in the post-RETAIN era (i.e. after June 2016) were more likely to restart ART (adjusted hazard ratio 1.50; 95% CI 1.34 -1.69), compared to earlier time periods.(30)

# OTHER SUPPORTS
In addition, supports such as counselling and use of motivational interviewing methods may improve retention and adherence to medication. (17,31) Motivational interviewing techniques can be delivered by mental health clinicians or by trained peer outreach workers.(32)
Interventions using phone text messaging can help to provide remote clinic support for individuals receiving ART. (6) In BC, the WelTel intervention has been shown to improve adherence to ART and virologic suppression among women with an unsuppressed viral load at the Oak Tree Clinic.(33, 34)