Pregnancy and contraceptive use among participants of childbearing potential in the HVTN 705 HIV vaccine trial in southern Africa

Pamela Mda¹Kathryn Therese Mngadi²Bo Zhang³Randy Burnham³Michal Juraska³Ollivier Hyrien³Nigel Garrett^4,5Thozama Dubula¹Sinalo Toni¹Sibi Joseph¹Phillip Kotze⁶Susan Buchbinder^7,8Azwi Takalani⁹Frank Tomaka¹⁰Alexander Luedtke³Wouter Willems¹¹Edith Swann¹²Julia Hutter¹²Huub Gelderblom³Margaret Juliana McElrath³Ludo Lavreys¹¹Lynda Stranix-Chibanda¹³Alison C. Roxby^14,3*Linda-Gail Bekker^15,5Glenda Gray¹⁶

• ¹Walter Sisulu University, Mthatha, South Africa
• ²Aurum Institute, Johannesburg, South Africa
• ³Fred Hutchinson Cancer Center, Seattle, Washington, United States
• ⁴Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa
• ⁵Desmond Tutu Health Foundation, Cape Town, South Africa
• ⁶Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa
• ⁷San Francisco Department of Public Health, San Francisco, California, United States
• ⁸University of California, San Francisco, San Francisco, California, United States
• ⁹Hutchinson Centre Research Institute of South Africa, Johannesburg, South Africa
• ¹⁰Janssen Pharmaceuticals, Inc., Titusville, New Jersey, United States
• ¹¹Janssen Research and Development (Belgium), Beerse, Belgium
• ¹²Division of AIDS, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States
• ¹³University of Zimbabwe, Harare, Zimbabwe
• ¹⁴University of Washington, Seattle, United States
• ¹⁵University of Cape Town, Cape Town, South Africa
• ¹⁶South African Medical Research Council, Pretoria, South Africa

HIV vaccine trial participants include sexually active cisgender females who agree to avoid pregnancy during the active vaccination period. Nevertheless, some pregnancies occur in almost all studies. We examined contraceptive use, pregnancy incidence, and the relationship between pregnancy and HIV seroconversion in one HIV vaccine trial.We performed an exploratory analysis of data collected for HVTN 705/HPX2008, a phase IIb HIV vaccine trial enrolling cisgender women across 23 sites in five southern African countries.Baseline characteristics and contraceptive use were assessed among participants who became pregnant and those who did not during the active vaccination phase (months 0-15). Pregnancy incidence rates were calculated for this phase and the duration of follow up (36 months). Cox regression analysis was used to assess factors associated with incident pregnancy.There were 2636 participants who received at least one vaccine or placebo dose (mean age: 23 years, standard deviation: 3 years). At enrolment, when contraception was required, 62.9% reported using injectable contraceptives. Overall pregnancy rate was 2.95 per 100 person-years (95% CI: 2.40, 3.58), with 101 pregnancies reported by month 15. Cumulative incidence of pregnancy at month 15 was similar between trial arms (log-rank p=0.688). Each additional year of age was associated with an 8% decrease in pregnancy incidence (p=0.014). Women aged 31-35 years had the lowest pregnancy incidence (1.75 [0.48, 4.48] per 100 person-years). In a Cox regression analysis covering months 0-15, all contraceptive methods significantly reduced the incidence of pregnancy compared to no contraceptive use. Oral contraception was associated with the least reduction in pregnancy risk; implants were associated with the most reduction in pregnancy risk (p<0.001).In HVTN 705/HPX2008, higher incidence of pregnancy was associated with younger age and oral contraception (compared to other methods). These data may inform future designs of HIV prevention or vaccine trials.