HIV Infections
Conditions
Brief summary
This study will evaluate the virologic effect, safety and tolerability of Genvoya® in adults during early acute HIV infection.
Detailed description
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.
Interventions
Participants will receive 1 tablet per day throughout study duration (96 weeks).
Sponsors
Gilead Sciences
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
prospective, open-label study
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. First identified as an incident HIV infection within one year of estimated time of infection in RV 217. 2. Willing to begin Genvoya® as soon as entering this study but not later than 7 days from study enrollment. 3. Successfully passed Test of Understanding (TOU) with a score of 80% or more on ten questions after three attempts. 4. Adult from 18 to 50 years of age. 5. Able to participate for 96 weeks of study visits 6. In general good health as determined by the PI or his/her designee 7. Willing to have photo or fingerprint taken for identification purposes 8. 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 9. Willing to have blood samples collected and stored. 10. Adequate renal function: estimated creatine clearance of \>50 mL/min according to the Cockroft Gault formula 2 weeks prior to enrollment 11. Urine clean catch: glucose \< trace and protein \<1+ or as per site-specification 2 weeks prior to enrollment 12. Weight is \> 35 kg 13. 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
1. 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. 2. Untreated AIDS-related opportunistic infection 3. An AIDS defining condition diagnosed within 30 days 4. Positive Hepatitis B surface antigen at any time in the past 5. Requiring use of any medication that is contraindicated with Genvoya®. See Appendix I and the package insert 6. Women who are breast-feeding There are no inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma viral load | Measured at 48 weeks after enrollment | The number of study participants with plasma viral load \<50 copies/mL |
| Treatment Discontinuation for AEs up to 96 weeks | Measured through week 96 | Tolerability of treatment as measured by treatment discontinuation for AEs up to 96 weeks |
| Drug-related AEs and SAEs | Measured through week 96 | Occurrence of drug-related adverse events and serious adverse events at any time from enrollment up to 96 weeks after enrollment early HIV infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4+ T cell count change | Measured over 48 weeks | CD4+ T cell count change over first 48 weeks as compared to baseline.following the initiation of Genvoya® |
| Frequency of HIV-related illnesses | Measured through week 96 | Frequency of HIV-related illnesses (including acute retroviral syndrome) |
| Duration of HIV-related illnesses | Measured through week 96 | Duration of HIV-related illnesses (including acute retroviral syndrome) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Markers of Immune Activation | Measured through week 96 | Description of markers of immune activation (soluble and cellular markers) by ICS. |
| Host humoral (IgG) responses | Measured through week 96 | Characterization of evolution in host humoral (IgG) responses to HIV envelope over time including development of neutralizing antibody responses |
| HIV reservoir size | Measured through week 96 | Evaluation of the HIV reservoir size by measurement of 1) single copy HIV RNA quantification in samples with HIV RNA \<50 copies/mL and 2) total HIV DNA and integrated HIV DNA in peripheral blood |
| Neuropsychological battery performance | Measured through week 96 | Evaluation of neuropsychological battery performance at week 48 and 96; and to later compare to RV 217 data from pre-infection and baseline early or acute HIV infection timepoints. |
| Changes in HIV-specific immune responses over time | Measured through week 96 | Description of changes in HIV-specific immune responses over time as characterized by intracellular cytokine staining (ICS) |
Countries
Uganda
Outcome results
None listed