Principal Investigator - Dr. Shahin Lockman MD, MPH
Study Objectives
Primary Objectives
- Efficacy: To evaluate the relative efficacy of oral CAB/CAB LA (oral run-in and injections, Steps 1 and 2) vs. daily oral TDF/FTC for HIV prevention (Steps 1 and 2).
- Safety: To evaluate the relative safety of oral CAB/CAB LA (oral run-in and injections, Steps 1 and 2) vs. daily oral TDF/FTC for HIV prevention (Steps 1 and 2).
Secondary Objectives
- To compare HIV incidence among participants receiving oral CAB/CAB LA vs. daily oral TDF/FTC (Steps 1, 2 and 3).
- To evaluate relative efficacy of oral CAB/CAB LA vs. oral TDF/FTC in subgroups defined by the baseline factors of: age, herpes simplex virus-2 (HSV-2) serostatus, contraceptive method, and body mass index (BMI).
- To describe and model the relationship between HIV incidence and drug concentration, within each arm.
- To describe the distribution and correlates of drug concentration, within each arm.
- To compare the acceptability of and preferences for CAB LA vs oral TDF/FTCA Study Design: Multi-site, double blind, two-arm, randomized (1:1), controlled superiority trial of the safety and efficacy of CAB LA compared to daily oral TDF/FTC for HIV prevention.
Study Population: HIV-uninfected women at risk for acquiring HIV, 18 to 45 years old.
Study Size: 3223 total enrolled participants globally.
Study Status: Enrolments complete and participants on follow-up. Unblinding of participants ongoing, following release of preliminary study results.
Study Duration: Approximately 4.6 years total, with individual participants being followed on randomized study product between 1.6 years to approximately 3.6 years.
Sponsors
- Division of AIDS (DAIDS), United States (US)
- National Institute of Allergy and Infectious Diseases (NIAID)
- US National Institutes of Health (NIH)
Overall, HPTN 084 enrolled 3,223 cisgender women at research sites in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. The average age of study participants was 26 years and 57% of participants were 18-25 years old. Eighty-two percent of the women enrolled were not living with a partner, 55% reported two or more partners in the past month, with 34% having a primary partner who is reported to be living with HIV or having an unknown HIV status. A total of 38 HIV infections occurred during follow-up, with four infections in the CAB LA arm (incidence rate 0.21%) and 34 infections in the FTC/TDF arm (incidence rate 1.79%). The hazard ratio in the CAB LA versus FTC/TDF arm was 0.11 (95% CI 0.04-0.32). Approximately nine times more incident HIV infections occurred in the FTC/TDF arm than in the CAB arm. These results meet the statistical criteria for superiority of CAB LA compared to FTC/TDF in the HPTN 084 study population. The higher-than-expected level of adherence to FTC/TDF throughout the study and overall low incidence rate in both arms of the study clearly demonstrate both drugs were highly effective at preventing HIV acquisition.
