HIV/AIDS
Conditions
Keywords
HIV/AIDS, Same-Day ART, Genvoya, Efavirenz
Brief summary
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
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.
Interventions
DRUGElvitegravir, Cobicistat, TAF, FTC
Started on day of HIV diagnosis
DRUGEfavirenz, TDF, and 3TC
Started on day of HIV diagnosis
Sponsors
Gilead Sciences
Brigham and Women's Hospital
Weill Medical College of Cornell University
Analysis Group, Inc.
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Same-Day ART with Genvoya vs. EFV/TDF/3TC
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 48-week viral suppression | 48 weeks after enrollment | To compare the proportion of participants who are retained in care with a plasma HIV-1 RNA level \<200 copies/ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 12-week viral suppression | 12 weeks after enrollment | Proportion of participants who are retained in care with a plasma HIV-1 RNA level \<200 copies/ml |
| Baseline resistance to ART medications | Baseline | Genotypic resistance to EFV and/or nucleoside reverse transcriptase inhibitors |
| Change in CD4 count | 48 weeks after enrollment | Median change in CD4 count over the study period (baseline to 48 weeks) |
| Virologic failure | 48 weeks after enrollment | Proportion of patients meeting the WHO definition for ART treatment failure over the study period |
| Adverse events | 48 weeks after HIV testing | 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 |
| Neurologic or psychiatric adverse event | 48 weeks | 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 |
| Sleep Quality | 4, 12, 24, and 48 weeks after enrollment | Mean scores on the Pittsburgh Sleep Quality Index |
| Depression | 4, 12, 24, and 48 weeks after enrollment | Mean scores on the Patient Health Questionnaires (PHQ-9) Questionnaire |
| Change in ART drugs | 48 weeks after HIV testing after enrollment | Proportion of participants who discontinue any drug in the original ART regimen |
Outcome results
None listed