Over the past 25 years, more than 30 major grants from the US government, private foundations, and industry have been awarded for collaborative research in Mombasa. Research supported by these grants has examined a range of topics relating to HIV and STD acquisition, transmission, treatment, and prevention.
Research Past and Present
Specific research focus areas have included:
- Examining the role of antiretroviral therapy in influencing the risk of HIV-1 transmission
- Effects of genital tract infections and the vaginal microbiome on women’s risk of acquiring and transmitting HIV-1
- Trials of interventions to reduce the risk HIV-1 and STI acquisition and transmission
- Evaluating the genomic evolution of HIV-1 following infection in an effort to understand the virological and immunological characteristics that determine the course of disease
- Characterizing the frequency of HIV-1 superinfection versus primary infection to evaluate the possible protective effect of natural HIV infection against re-infection
- Over 225 manuscripts presenting the findings from these studies have been published in peer-reviewed journals
Research Agenda For 2018
- NIH/NIAID supported studies of HIV-1 seroconverters during early and chronic infection will continue in an effort to define virological and immunological correlates of immune control.
- Through this research, we hope to inform the development of novel strategies for HIV vaccine development.
- NIH Fogarty International Center supported study to assess HPV preparedness among youth in Mombasa County.
- This study will explore several factors influencing HPV vaccine preparedness in Mombasa County, including both in- and out-of-school girls.
- NIH/NICHD funded implementation science study to assess the effectiveness, costs, and budget impact of implementing systems analysis and improvement approach to increase HIV testing in Family Planning (FP) clinics in Mombasa County.
- This study, which was developed in collaboration with Mombasa County, will provide strong evidence to guide integration of HIV testing into FP services.
- NIH/NICHD supported study entitled, Impact of periconceptual vaginal microbiota on women’s risk of preterm birth.
- This study will address the hypothesis that the vaginal microbiota present near to the time of conception is a major driver of spontaneous preterm birth.
- NIH/NCI supported study, “Development and evaluation of a point of care cervical cancer screening test”
- This study is currently in the pre-clinical phase. If NIH approves moving to the clinical phase, we will screen ~2000 women for cervical cancer with both standard diagnostics a new point of care diagnostic test.
- A Hologic funded study is investigating the feasibility of self-collection of samples for high-risk HPV testing as a cervical cancer screening approach.
- Self-collection could provide a useful approach for increasing access to cervical cancer screening and reducing cervical cancer deaths.
Examples of abstracts from recent publications include:
Key Vaginal Bacteria Associated with Increased Risk of HIV Acquisition in African Women: A Nested Case-Control Study (In Press Lancet Infect Dis)
Background: Disruptions of vaginal microbiota may increase women’s susceptibility to HIV infection. Advances in molecular microbiology have enabled detailed examination of associations between vaginal bacteria and HIV acquisition. This prospective study utilized molecular characterization of vaginal microbiota to examine the link between vaginal bacteria and risk of HIV acquisition.
Methods: Data from five cohorts of African women including sex workers, pregnant/post-partum women, and women in serodiscordant relationships were utilized to conduct a nested case-control analysis comparing vaginal microbiota between women who acquired HIV (cases, N=87) versus women who remained seronegative (controls, N=262). First, deep sequence analysis of broad-range 16S rRNA gene polymerase chain reaction (PCR) products was applied to a subset of 55 cases and 55 controls. From these data, 20 taxa were selected for bacterium-specific quantitative PCR (qPCR) assays, which were examined in the full cohort.
Findings: Vaginal bacterial community diversity, measured by the Shannon Diversity Index, was higher in women who acquired HIV (median 1.3, interquartile range [IQR] 0.4-2.3) compared to seronegative controls (median 0.7, IQR 0.1-1.5), p=0.03. Seven taxa, Parvimonas species Types 1 and 2, Gemella asaccharolytica, Mycoplasma hominis, Leptotrichia/Sneathia, Eggerthella species Type 1, and vaginal Megasphaera species showed significant concentration-dependent associations with up to >4.5-fold increased odds of HIV acquisition after adjusting for potential confounding factors.
Interpretation: Vaginal microbial diversity and concentrations of key bacteria were associated with women’s risk of HIV acquisition. Defining vaginal bacterial taxa associated with HIV risk could point to mechanisms influencing HIV susceptibility and provide important targets for future prevention research.
Comprehensive Characterization of Humoral Correlates of Human Immunodeficiency Virus 1 Superinfection Acquisition in High-risk Kenyan Women (EBioMedicine. 2017 Apr 18;216-224)
HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6 months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design. We evaluated a panel of humoral immune responses in the largest published group of superinfected individuals (n=21), compared to a set of 3:1 matched singly infected controls from the same cohort. The immune functions studied included plasma neutralization, plasma and cervical antibody-dependent cellular cytotoxicity, and plasma IgG and IgA binding to a panel of 18 envelope antigens, including correlates of HIV acquisition in the RV144 vaccine trial, IgG binding to V1V2 and IgA binding to gp140. Association between each immune function and HIV superinfection was evaluated using conditional logistic regression. No significant associations were detected between any of the immune functions and superinfection acquisition. This study constitutes the most comprehensive and detailed characterization of multiple immune correlates of superinfection to date. The results suggest that immune responses not commonly measured in current HIV studies may be important in protection from HIV infection, and these or a more robust humoral response than that seen in naturally infected women may be needed for a protective vaccine.