Tenofovir microbicide gel as an effective prophylactic measure to human herpes virus-8.

Abstract

Background: High prevalence and incidence rates of human herpes virus-8 (HHV-8) contributes significantly in the aetiology of cancers, including Kaposi sarcoma (KS). These cancers remain among leading causes of morbidity and mortality especially in people who are immunocompromised. Aim: To determine the effectiveness of 1% topical tenofovir disoproxil fumarate (TDF) as a vaginal gel formulation on HHV-8 acquisition amongst participants enrolled in the CAPRISA 004 trial. Methods: The CAPRISA 004 trial was a randomised controlled trial which investigated the effect of TDF gel on Human immunodeficiency virus (HIV) acquisition. A total 889 women from urban and rural settings in KwaZulu-Natal, aged 18 to 40 years were enrolled in the study and the samples from these women were tested for HHV-8 infections. Peripheral blood samples collected at enrolment and at the study exit visit were tested with Biotrin’s indirect immunofluorescent system to measure antibody to HHV-8 lytic antigens. HHV-8 prevalence was evaluated by sociodemographic factors and incidence by study arm and location. Descriptive statistics included means and standard deviation for quantitative data and frequencies for categorical data with Fisher’s exact test. Poisson regression was used to evaluate the incidence rate. A two-tailed p-value of less than 0.05 was considered significant in hypothesis testing and 95% confidence intervals (95% CI) are reported. Results: At baseline testing, 54 of 889 participants were HHV-8 positive with a prevalence of 6.12%. A higher parity (p=0.014) and higher number of sexual partners (p<0.001) as well as a rural setting (p=0.014) were associated with higher prevalence. With 40 infections among the 660 participants, the overall HHV-8 incidence rate was 3.98 per 100 person-years (PY) (95% Confidence Interval [CI] 2.84-5.42). Twenty infections occurred among participants assigned to the TDF arm with an HHV-8 incidence rate of 4.05 per 100 PY (95% CI 2.48-6.26) compared to the 20 infections among participants assigned to the placebo arm with an HHV-8 incidence rate of 3.91 per 100 PY (95% CI 2.39-6.04) (Incidence rate ratio (IRR) of 1.04, 95% CI 0.56-1.93; p=0.909). There were no differences in the HHV-8 incidence rates among participants assigned to the TDF and placebo arms in rural (IRR 1.40, 95% CI 0.66-2.95), p=0.383 or urban settings (IRR.51, 95% CI 0.15-1.68), p=0.266. HIV incidence rate among participants with prevalent HHV-8 infections was 6.48 per 100 PY (95% CI 2.11-15.13) and was similar to the HIV incidence rate of 7.35 per 100 PY (95% CI 5.92-9.01) among participants who remained HHV-8 negative, IRR of 0.88 (95% CI 0.36-2.17), p=0.785. Conclusion: The study showed that among women in rural and urban settings in KwaZulu-Natal, South Africa, the prevalence of HHV-8 infection was high and that TDF was not effective in the prevention of HHV-8 infection.