Antiretroviral Therapy for Acute HIV Infection

Study Overview
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Brief Summary
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This study will evaluate the virologic effect, safety and tolerability of Genvoya® in adults during early acute HIV infection.

Detailed Description
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This is a prospective, open-label study to describe the effects of early antiretroviral (ART) therapy on 1) viral load, 2) safety and tolerability of Genvoya®, 3) clinical outcomes and secondarily on HIV-specific immune responses. This study is a sub-study of RV 217 that will recruit participants with incident HIV diagnoses from the parent RV 217 cohort. Potential RV 392 volunteers will be recruited from the RV 217 ECHO cohort if they have been diagnosed with incident HIV Infection. Screening procedures for HIV in RV 217 are designed to identify participants during acute HIV infection (AHI) or early HIV infection. Participants will initiate Genvoya®, a once a day antiretroviral pill within 1 week of enrollment. RV 392 follow-up visits will largely overlap with RV 217 visits for the study duration of 96 weeks, but additional visits will occur early after initiation of Genvoya®. RV 392 participants will remain co-enrolled in RV 217 (i.e., RV 217 visits also continue); blood collection will be coordinated by the RV 392 team by prioritizing safety labs and then research labs within the allotted blood volumes while still meeting scientific objectives for both RV 217 and RV 392. Blood tests that are required for both protocols will only be collected once and will not be duplicated across the two protocols.

Official Title
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Antiretroviral Therapy for Acute HIV Infection

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First identified as an incident HIV infection within one year of estimated time of infection in RV 217. Willing to begin Genvoya® as soon as entering this study but not later than 7 days from study enrollment. Successfully passed Test of Understanding (TOU) with a score of 80% or more on ten questions after three attempts. Adult from 18 to 50 years of age. Able to participate for 96 weeks of study visits In general good health as determined by the PI or his/her designee Willing to have photo or fingerprint taken for identification purposes No history of ART for any reason, i.e., treatment naïve and no HIV-post-exposure prophylaxis (PEP) or HIV-pre-exposure prophylaxis (PrEP)) within 90 days prior to enrollment Willing to have blood samples collected and stored. Adequate renal function: estimated creatine clearance of >50 mL/min according to the Cockroft Gault formula 2 weeks prior to enrollment Urine clean catch: glucose < trace and protein <1+ or as per site-specification 2 weeks prior to enrollment Weight is > 35 kg Female (only women of childbearing potential) Specific Criteria: Negative pregnancy test 48 hours prior to enrollment: Commits to continued use of adequate birth control method for 96 weeks of the study and prior to receiving study ART. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted, underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms, intrauterine device (IUD), or abstinence. If depending on hormonal contraception, check package insert for drug interactions and/or consider adding a second barrier method. Exclusion Criteria: Any chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer, including but not limited to chronic hepatitis, renal insufficiency or failure; clinically significant forms of drug or alcohol abuse, mental illness, severe asthma, psychiatric disorders, heart disease, or cancer; or a physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, focal neurological deficit, etc. Untreated AIDS-related opportunistic infection An AIDS defining condition diagnosed within 30 days Positive Hepatitis B surface antigen at any time in the past Requiring use of any medication that is contraindicated with Genvoya®. See Appendix I and the package insert Women who are breast-feeding There are no inclusion/exclusion criteria based on CD4 count because CD4 count can be transiently diminished during acute HIV infection and ART initiation during early or acute HIV infection offers the potential benefit of limiting reservoir seeding and preventing immune destruction regardless of peripheral CD4 count at the time of treatment initiation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Intervention Model: Single Group Assignment
Interventional Model Description: prospective, open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet<br>Genvoya® (Elvitegravir, corbiscistat, Emtricitabine and Tenofovir Alafenamide): once a day antiretroviral pill starting within 1 week of enrollment. | Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet<br>* Participants will receive 1 tablet per day throughout study duration (96 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma viral load | The number of study participants with plasma viral load <50 copies/mL | Measured at 48 weeks after enrollment | 
| Plasma viral load | The number of study participants with plasma viral load <50 copies/mL | Measured at 96 weeks after enrollment | 
| Drug-related AEs and SAEs | Occurrence of drug-related adverse events and serious adverse events at any time from enrollment up to 96 weeks after enrollment early HIV infection. | Measured through week 96 | 
| Treatment Discontinuation for AEs up to 96 weeks | Tolerability of treatment as measured by treatment discontinuation for AEs up to 96 weeks | Measured through week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ T cell count change | CD4+ T cell count change over first 48 weeks as compared to baseline.following the initiation of Genvoya® | Measured over 48 weeks | 
| Frequency of HIV-related illnesses | Frequency of HIV-related illnesses (including acute retroviral syndrome) | Measured through week 96 | 
| Duration of HIV-related illnesses | Duration of HIV-related illnesses (including acute retroviral syndrome) | Measured through week 96 |