HVTN 097: Evaluation of the RV144 Vaccine Regimen in HIV Uninfected South African Adults

Background: Following the RV144 trial demonstration of 31% vaccine efficacy in preventing HIV infection in Thailand, HVTN 097 was designed to evaluate the same regimen in South Africans to ascertain whether their immune response profiles were similar to Thais. This study was conducted in preparation for evaluating a similar clade C HIV vaccine regimen in South Africa. Our study was critical as previous studies have demonstrated that age, gender and BMI impact vaccine-induced immune responses.

Methods: ALVAC-HIV (vCP1521) expressing HIV-1 Env (clade E, gp120 from strain 92TH023 and clade B TM gp41 from strain HIV_Lai, and Gag and protease (clade B) was administered at baseline then 1, 3 and 6 months later with AIDSVAX^® B/E, bivalent HIV gp120 subtypes B (MN) and E (A244) adsorbed to alum at the last 2 vaccinations. Immune responses were measured 2 weeks after the last immunization. Intracellular Cytokine Staining identified response rates and frequencies of HIV-specific T cells expressing IFN-γ and/or IL-2. Binding antibodies to HIV-1 gp120 and V1V2, IgG subclass, and antibody functions (ADCC, avidity index, nAb, and virion capture) are ongoing. Immune responses were stratified by age, gender and BMI.

Results: In 68 participants, overall peak response rates of Env-specific CD4+ T cells expressing IFN-γ and/or IL-2 was 70.6% (95% CI 58.9%, 80.1%), similar to or greater than responses in RV144. Although not significant, participants <25 years old had higher response rates observed than those ≥26 (76.0% vs. 55.6%, p = 0.108). Response rates in females (75%; 95%CI 56.6%, 87.3%) were similar to males (67.5%; 95%CI 52.0%, 79.9%). Response rates stratified by BMI categories of <25, 25–30, >30 were 63.6%, 82.4% and 85.7%, respectively (p < 0.1 for BMI ≥ 25).

Conclusions: Response rates and magnitudes of Env-specific CD4+ T cells in South Africans induced by the same vaccine regimen used in RV144 were at least comparable to or better than those induced in RV144. Age/gender or BMI did not affect CD4+ T-cell response rates.