Control of sexually transmitted infections in a high prevalence region : HIV, syphilis and HBV among young adults and preparation for HIV vaccine trials in Mozambique

Abstract: Mozambique is one of the countries with a high burden of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis. HIV seroprevalence in adults was estimated to be 11.5% in 2009, syphilis prevalence among women was estimated to be 5.7% in 2010 and an estimated national HBV prevalence of above 8%. These infections are sexually transmitted and co- infections are common. The availability of data on prevalence and incidence of these infections, and risk factors related to their spread, is crucial for designing prevention strategies and in order to successfully conduct clinical intervention studies. Additionally, a safe, efficacious and affordable HIV vaccine would be ideal to better control the HIV epidemic. In study I, we prospectively enrolled (n=1380) and followed up a cohort of young adults (n=1309, HIV seronegative participants) to determine their suitability for possible participation in phase I/II HIV vaccine trials through determination of prevalence and incidence of HIV. We also determined the prevalence of HBV and syphilis. The incidence of HIV in this group was 1.14/100PY. The prevalence of HIV, HBV and syphilis was 5.1%, 12.2% and 0.36%, respectively. In study II, we determined the prevalence of HBV seromarkers in 1377 young adults in Maputo, Mozambique. The age-specific changes of prevalence of HBsAg and Anti-HBc was used to estimate the incidence of HBV using catalytic modelling. The overall prevalence was 42.8% for exposure to HBV (anti-HBc+), 12.1% for HBV infection (HBsAg+), 8.5% for chronic carriers (HBsAg+ and anti-HBc+) and 3.6% for acute infection (HBsAg+ only). The incidence of HBV was 180 per 100,000 PY using HBsAg and 2690 per 100,000 PY using anti-HBc. In study III, a cross sectional study was conducted at a youth clinic in Maputo, Mozambique, to establish, for the first time, clinical laboratory reference values in the country. The hematological and biochemistry reference values derived from 257 healthy Mozambican young adults differed from those derived from a North American population. In study IV, a phase I trial was conducted to assess the safety and immunogenicity of HIV-DNA delivery using the Zetajet TM, a needle-free device, in a volume of 0.2 ml (3 mg/ml) intradermally followed by HIV-MVA boosts. The volunteers were randomized to receive three immunizations of 600 μg (2 x 0.1 ml, standard injection) (n = 10) or 1200 μg (2 x 0.2 ml) (n = 10) of HIV-DNA, followed by two 108 pfu HIV- MVA boost vaccinations. Four subjects received placebo. After the first HIV-MVA, Env responses were significantly higher in the high-dose group compared to the low-dose group (median 420 vs. 157.5 SFC/million PBMC, p = 0.014). Preliminary data show that the frequency of responders with antibodies against HIV Env antigens in the V2 loop was significantly higher in the high-dose group than in the low-dose group, 6/8 (75%) vs. 2/8 (25%), respectively, p = 0.0486. The high dose of HIV-DNA induced the higher average number of Env-reactive antigen features in the V2 loop than the low dose. Conclusion: The prevalence and incidence of HIV in the youth cohort in Maputo was relatively low, suggesting that this group is suitable for recruitment into a phase I/II HIV vaccine trial. The prevalence and incidence of HBV was high among young adults in Mozambique. Therefore, further HBV prevention strategies should be implemented, including catch-up vaccinations for children and adolescents, screening of pregnant women and vaccination of adults at risk of exposure. The clinical laboratory reference values established here highlight the need for establishing region-specific values for proper patient management and the safe conduct of clinical trials in Mozambique. The last study demonstrated that priming with a high dose of HIV-DNA is safe and suggests an immunological advantage over the lower HIV-DNA dose.