HIV Test and Treat to Prevent HIV Transmission Among MSM and Transgender Women

Study Overview
=================
Brief Summary
-----------------
This study will recruit men and transgender women with acute or recent HIV infection. It wil look at how HIV medicines (ART) when given very early after HIV infection affect the amount of HIV in the blood, semen and rectal secretions. In addition, Investigators will be using modeling studies to look at whether or not this kind of HIV treatment can decrease the risk that a man will infect a person he has sex with and to find out how failure to take medications will impact spreading the virus to other people. In this study, one group will be randomized (like a coin toss) to start ART immediately (just at the time of the enrollment visit) and the other group will wait until week 24 of the study to start ART. Both groups will be followed for a total of 48 weeks and will continue to receive ART from local sources after the study is over.

Detailed Description
-----------------
This is three-step study. Step 1 will screen men who have sex with men (MSM) and transgender women who are unaware of their HIV status and 1) report high risk behaviors for acquiring HIV-1 infection or 2) who have symptoms of acute retroviral syndrome or 3) who have a sexual partner with newly-diagnosed acute or recent HIV infection. HIV testing will be conducted for several thousand MSM and transgender women from study opening until July 2015. In Step 2, high risk HIV-1 uninfected MSM and transgender women with high risk for acquiring HIV will be tested at regular intervals for incident HIV-1 (using tests for HIV p24 and/or HIV RNA). (During this period, men will receive standard HIV prevention interventions.) In Step 3, individuals with acute or recent HIV-1 infection will be enrolled in a 48-week randomized, open-label study of the effects of immediate vs. deferred ART on the decay dynamics of HIV viral load in plasma, semen and rectal secretions. (ART will be provided prior to 24 weeks for any participant in the deferred ART arm who meets initiation criteria.) All participants will be followed for 48 weeks after which they will continue ART from other sources.

Official Title
-----------------
HIV Testing and Treatment to Prevent Onward HIV Transmission Among MSM and Transgender Women in Lima, Peru

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Drug: Atripla or Stribild


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult men who have sex with men, and transgender women Unaware of HIV status at enrollment in follow-up cohort High risk for HIV infection Willing to test for HIV No prior ART, including prior administration of pre- and post-exposure prophylaxis in the last 30 days Willing to provide informed consent Exclusion Criteria: Prior receipt of investigational anti-HIV vaccine Ongoing therapy with any of the following: Systemic corticosteroids. Short course less than or equal to 21 days of corticosteroids is allowed Systemic chemotherapeutic agents Nephrotoxic systemic agents, including aminoglycosides, amphotericin B, cidofovir, cisplatin, foscarnet, pentamidine Immunomodulatory treatments including Interleukin-2 Investigational agents Known allergy/sensitivity or any hypersensitivity to components of study drugs (ART) or their formulations Active drug or alcohol use or dependence that would interfere with adherence to study requirements Serious medical or psychiatric illness that would interfere with the ability to adhere to study requirements Chronic or acute hepatitis B infection Use of female hormonal products based on estrogen or derivatives

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate ART (Atripla or Stribild)<br>Daily Atripla or Stribild will be provided to these patients for the duration of the study beginning at enrollment. | Drug: Atripla or Stribild<br>* Antiretroviral therapy<br>* Other names: (alternate: Truvada + 3rd ARV);|
| Placebo Comparator: Deferred ART (Atripla or Stribild)<br>Daily Atripla or Stribild will be provided to these patients for the duration of the study beginning at 24 weeks. | Drug: Atripla or Stribild<br>* Antiretroviral therapy<br>* Other names: (alternate: Truvada + 3rd ARV);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HIV Viral Load Suppression in Plasma | To quantify HIV viral load suppression (<1000 copies/mL) in plasma at Baseline and weeks 12, 24, 36, and 48 weeks Suppressed at Baseline = HIV Viral load measured at the time of enrollment was <1000 copies/mL Suppressed at Week 12 = HIV Viral load measured 12 weeks after enrollment was <1000 copies/mL etc. | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Number of Participants With HIV Viral Load Suppression in Semen | To quantify HIV viral load suppression (<1000 copies/mL) in semen at Baseline and weeks 12, and, 24 weeks | Baseline, Week 12, and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequence Clusters Identified Using Phylogenetic Analysis Among Participants With Early HIV Infection | HIV present in blood samples from recently infected study participants was sequenced. Sequences that were similar to each other were grouped together in clusters. For this analysis, clusters were defined using a patristic distance threshold of 0.01, and a minimum cluster size of two. | HIV diagnosis visit | 
| Percent of Participants Whose HIV Sequences Appear in Phylogenetically Defined Clusters | HIV present in blood samples from recently infected study participants was sequenced. Sequences that were similar to each other were grouped together in clusters. For this analysis, clusters were defined using a patristic distance threshold of 0.01, and a minimum cluster size of two. | HIV diagnosis visit | 
| Number of Participants Diagnosed With Acute HIV Infection Who Were Linked to Care | To determine the proportion of individuals with evidence of acute infection (HIV-1 RNA-positive) who are successfully contacted for confirmatory HIV testing and are then linked to care. | within 3 months of diagnosis of acute HIV infection | 
| Partner Tracing | Partner tracing and notification | within 3 months of diagnosis | 
| Number of Participants Retained in Care | To determine the number of participants who were retained in care at weeks 12, 24, 36, and 48 | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Adherence to ART Regimen (Percentage of Pills Taken) | To determine percentage of ART pills taken by participants randomized to immediate and deferred ART initiation. | 48 weeks | 
| Adherence to Viral Load (VL) Procedure | To determine the number of participants who had a viral load test at Baseline and weeks 12, 24, 36, and 48 | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Adherence to CD4 Procedure | To determine the number of participants who had a CD4 test at Baseline and weeks 12, 24, 36, and 48 | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Adherence to Questionnaires | To determine the number of participants who completed the Computer Assisted Self interviews (CASI) at Baseline and weeks 12, 24, 36, and 48 | Baseline, Week 12, Week 24, Week 36, and Week 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Treatment as Prevention, Seek, Test, Treat, Retain Strategies