Cervical Dysplasia, Infection, and Phylogeny of Human Papillomavirus in HIV-Infected and HIV-Uninfected Women at a Reproductive Health Clinic in Nairobi, Kenya.

High risk human Papillomavirus (HPV) infections ultimately cause cervical cancer. Human Immunodeficiency Virus (HIV) infected women often present with multiple high-risk HPV infections and are thus at a higher risk of developing cervical cancer. However, information on the circulating high-risk HPV genotypes in Kenya in both HIV-infected and HIV-uninfected women is still scanty. This study is aimed at determining the phylogeny and the HPV genotypes in women with respect to their HIV status and at correlating this with cytology results. This study was carried out among women attending the Reproductive Health Clinic at Kenyatta National Hospital, a referral hospital in Nairobi, Kenya. A cross-sectional study recruited a total of 217 women aged 18 to 50 years. Paired blood and cervical samples were obtained from consenting participants. Blood was used for serological HIV screening while cervical smears were used for cytology followed by HPV DNA extraction, HPV DNA PCR amplification, and phylogenetic analysis. Out of 217 participants, 29 (13.4%) were HIV seropositive, while 68 (31.3%) were positive for HPV DNA. Eight (3.7%) of the participants had abnormal cervical cytology. High-risk HPV 16 was the most prevalent followed by HPV 81, 73, 35, and 52. One participant had cervical cancer, was HIV infected, and had multiple high-risk infections with HPV 26, 35, and 58. HPV 16, 6, and 81 had two variants each. HPV 16 in this study clustered with HPV from Iran and Africa. This study shows the circulation of other HPV 35, 52, 73, 81, 31, 51, 45, 58, and 26 in the Kenyan population that play important roles in cancer etiology but are not included in the HPV vaccine. Data from this study could inform vaccination strategies. Additionally, this data will be useful in future epidemiological studies of HPV in Nairobi as the introduction or development of new variants can be detected.

Co-Infection Burden of Hepatitis C Virus and Human Immunodeficiency Virus among Injecting Heroin Users at the Kenyan Coast.

BACKGROUND: Injection drug use is steadily rising in Kenya. We assessed the prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast. METHODS: A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation center program in Malindi were consented and screened for HIV-1 and HCV by serology and PCR and their CD4 T-cells enumerated by FACS. RESULTS: Prevalence of HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%) were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co-infection was higher among injectors aged 30 to 40 years (20.7%) and among males (22.1%) than comparable groups. About 35% of the injectors were receiving antiretroviral treatment (ART). Co-infection was highest among injectors receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3 overall, significantly lower for co-infected (mean, 146; 95% CI 114 - 179 cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 - 487 cells/mm3, p<0.001) or uninfected (mean, 618, 95% CI 549 - 687 cells/mm3, p<0.001) injectors and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 - 156 cells/mm3) than TDF (mean 607, 95% CI, 196 - 1018 cells/mm3, p=0.005) or AZT (mean 474, 95% CI -377 - 571 cells/mm3, p=0.004). CONCLUSION: Mono and dual infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is low. The co-infected IHUs have elevated risk of immunodeficiency due to significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as-prevention for both HIV and HCV and harm reduction should be scaled up to alleviate infection burden.

Susceptibility to Simian immunodeficiency virus ex vivo predicts outcome of a prime-boost vaccine after SIVmac239 challenge.

BACKGROUND: Efficacy assessment of AIDS vaccines relies both on preclinically challenging immunized monkeys with simian immunodeficiency virus (SIV) or monitoring infection rates in large human trials. Although conventional parameters of vaccine-induced immune responses do not completely predict outcome, existing methods for testing cellular immunity are sophisticated and difficult to establish in resource-limited settings. METHODS: We have used virus replication kinetics (VVR) on ConA-stimulated peripheral blood mononuclear cells from rhesus monkeys immunized with DNA replication-defective adenovirus vector expressing various SIV genes, as an ex vivo model, to mimic the effects of different immune effector functions on viral infection. RESULTS: VVR was attenuated by the immunization and correlated 2 weeks after first boost, with the number of interferon gamma-secreting cells and T-cell noncytotoxic antiviral responses. Importantly, VVR on the day of challenge but not interferon gamma responses correlated with viremia and with memory CD4+ T-cell measurements after SIVmac239 challenge. Similarly, T-cell noncytotoxic antiviral responses on the day of challenge correlated directly with memory CD4 T cell and inversely with plasma viremia after challenge. CONCLUSIONS: VVR thus served as a better predictor of protective capacity of the vaccine regimen in these monkeys. We suggest that VVR be considered in the evaluation of candidate AIDS vaccines in humans.

Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques.

We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-gamma and T-cell proliferation responses and mediated a conservation of CD4(+) memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.