Same-Day Treatment With Genvoya vs. EFV/TDF/3TC

Study Overview
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Brief Summary
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Randomized, open-label study comparing Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine (Genvoya) vs. Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine (EFV-TDF-3TC) in patients starting ART on the day of HIV diagnosis.

Detailed Description
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Patients with WHO Stage 1 or 2 disease at HIV diagnosis will be randomized in a 1:1 ratio to either the Genvoya group or the EFV-TDF-3TC group. ART will be initiated on the day of HIV diagnosis. Participants who are found to have a contraindication to their assigned treatment regimen will change ART, and be classified as a failure for their assigned treatment arm. Participants in the EFV-TDF-3TC group with CrCl of 30-50 mL/minute, or with baseline mutations that significantly reduce the susceptibility of EFV will switch to Genvoya. Participants in the Genvoya group who are diagnosed with TB after enrollment will be switched to an ART regimen that can be administered with rifampin. If the study physician determines that a treatment change is indicated due to intolerability or side effects, the relevant clinical data will be presented to a safety committee that is blinded to group assignment. The ART regimen will be changed if the safety committee determines that it is indicated, and the participant will be considered a failure to their assigned treatment group. Patients will be followed for 48 weeks.

Official Title
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An Open-Label, Randomized Comparison of Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine Versus Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine in Patients Starting Antiretroviral Therapy on the Day of HIV Diagnosis

Conditions
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HIV/AIDS

Intervention / Treatment
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* Drug: Elvitegravir, Cobicistat, TAF, FTC
* Drug: Efavirenz, TDF, and 3TC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of positive HIV status (test conducted at GHESKIO); At least 18 years of age; Unaware of HIV diagnosis prior to date of enrollment, and ART-naïve; Ability and willingness to give written informed consent; Ready to initiate same-day ART, according to two criteria: (1) HIV medication readiness questionnaire; and (2) social worker assessment; WHO Stage 1 or 2 disease, as defined by the following conditions: asymptomatic; persistent generalized lymphadenopathy; unexplained weight loss (under 10%); recurrent upper respiratory tract infections; herpes zoster; angular chelitis; recurrent oral ulcerations; papular pruritic eruptions; seborrheic dermatitis; or fungal nail infections. Female participants may be enrolled if they are either: (1) post-menopausal; (2) physically incapable of becoming pregnant due to tubal ligation, hysterectomy, or bilateral oophorectomy; or (3) are of childbearing potential, and agree to use one of the following methods to avoid pregnancy throughout the duration of the study: Complete abstinence from intercourse; Double barrier method, such as male condom/spermicide, male condom/diaphragm, or diaphragm/spermicide; Hormonal contraception plus a barrier method; Intrauterine device (IUD); Male partner sterilization (if participant has only one sexual partner); Exclusion Criteria: Pregnancy or breastfeeding at the screening visit; Active drug, alcohol use, or mental condition that would interfere with the ability to adhere to study requirements, in the opinion of the study physician; World Health Organization Stage 3 or 4 disease, as defined by the following conditions: unexplained severe weight loss (over 10% of presumed or measured body weight); unexplained chronic diarrhea for longer than 1 month; unexplained persistent fever (intermittent or constant for longer than 1 month); persistent oral candidiasis; oral hairy leukoplakia; pulmonary tuberculosis; severe bacterial infections (e.g. pneumonia, empyema, meningitis, pyomyositis, bone or joint infection, bacteremia, severe pelvic inflammatory disease); or acute necrotizing ulcerative stomatitis, gingivitis or periodontitis. Clinical evidence of cirrhosis (ascites or encephalopathy); Anticipated need for hepatitis C therapy during the study period; Baseline CrCl <30 mL/minute by the Cockcroft-Gault equation (late exclusion, as creatinine results will not be available at the time of enrollment); Either the K65R mutation or more than 3 thymidine analogue mutations on baseline resistance testing (late exclusions, after baseline resistance results are available). Planning to transfer care to another clinic during the study period;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Same-Day ART with Genvoya vs. EFV/TDF/3TC
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elvitegravir-Cobicistat-TAF-FTC<br>Elvitegravir 150mg po QD Cobicistat 150 mg po QD TAF 10 mg po QD FTC 200 mg QD | Drug: Elvitegravir, Cobicistat, TAF, FTC<br>* Started on day of HIV diagnosis<br>|
| Active Comparator: EFV-TDF-3TC<br>EFV 600 mg po QD TDF 300 mg po QD 3TC 300 mg po QD | Drug: Efavirenz, TDF, and 3TC<br>* Started on day of HIV diagnosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 48-week viral suppression | To compare the proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml | 48 weeks after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-week viral suppression | Proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml | 12 weeks after enrollment | 
| Baseline resistance to ART medications | Genotypic resistance to EFV and/or nucleoside reverse transcriptase inhibitors | Baseline | 
| Change in CD4 count | Median change in CD4 count over the study period (baseline to 48 weeks) | 48 weeks after enrollment | 
| Virologic failure | Proportion of patients meeting the WHO definition for ART treatment failure over the study period | 48 weeks after enrollment | 
| Adverse events | Proportion of participants with a new Division of AIDS Grade 3 or 4 adverse event or laboratory abnormality that is at least a one-grade increase from baseline | 48 weeks after HIV testing | 
| Neurologic or psychiatric adverse event | Proportion of participants with a new Division of AIDS Grade 1 to 4 neurologic or psychiatric disorder that is at least a one-grade increase from baseline | 48 weeks | 
| Sleep Quality | Mean scores on the Pittsburgh Sleep Quality Index | 4, 12, 24, and 48 weeks after enrollment | 
| Depression | Mean scores on the Patient Health Questionnaires (PHQ-9) Questionnaire | 4, 12, 24, and 48 weeks after enrollment | 
| Change in ART drugs | Proportion of participants who discontinue any drug in the original ART regimen | 48 weeks after HIV testing after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/AIDS, Same-Day ART, Genvoya, Efavirenz