Clinical trial NCT03877536: Antiretroviral Therapy for Acute HIV Infection
Official title: Antiretroviral Therapy for Acute HIV Infection
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: HIV Infections
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2019-03-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: prospective, open-label study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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/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.

Primary outcomes:
measure: Plasma viral load
timeFrame: Measured at 48 weeks after enrollment
measure: Plasma viral load
timeFrame: Measured at 96 weeks after enrollment
measure: Drug-related AEs and SAEs
timeFrame: Measured through week 96
measure: Treatment Discontinuation for AEs up to 96 weeks
timeFrame: Measured through week 96
Secondary outcomes:
measure: CD4+ T cell count change
timeFrame: Measured over 48 weeks
measure: Frequency of HIV-related illnesses
timeFrame: Measured through week 96
measure: Duration of HIV-related illnesses
timeFrame: Measured through week 96
Other outcomes:
measure: Changes in HIV-specific immune responses over time
timeFrame: Measured through week 96
measure: Host humoral (IgG) responses
timeFrame: Measured through week 96
measure: Markers of Immune Activation
timeFrame: Measured through week 96
measure: HIV reservoir size
timeFrame: Measured through week 96
measure: Neuropsychological battery performance
timeFrame: Measured through week 96
Locations:
city: Kampala
country: Uganda
facility: Makerere University--Walter Reed Project (MUWRP)
Study officials:
affiliation: Henry M. Jackson Foundation in support of MHRP
name: Christina Polyak, MD, MPH
role: STUDY_CHAIR
References: