In 2013, MHRP initiated a large, long-term cohort study at multiple African sites that evaluates HIV prevention and treatment services at MHRP-affiliated clinical care sites funded by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). The African Cohort Study (AFRICOS) allows MHRP to monitor the impact of HIV-directed health and preventive services in four African countries.
MHRP conducts and collaborates on cohort and epidemiologic studies in North America, sub-Saharan Africa, Europe, the Middle East and Southeast Asia. This type of research helps identify and characterize populations that are at risk for HIV and other sexually transmitted infections (STIs) to inform the development of prevention and treatment modalities. Biomedical and other interventions will be more effective when the needs and traits of the end beneficiary are considered from the outset. Developing relationships with key populations through observational research facilitates engagement of these population for future studies of product safety and efficacy. This foundational work will also inform eventual deployment of safe and efficacious products to the populations that need them most.
MHRP also conducts studies that help to optimize the implementation of care delivery in order to reduce morbidity and disease transmission. This includes research focused on HIV prevention and care services at PEPFAR-supported facilities. MHRP studies track health outcomes and performance indicators in populations impacted by HIV and other STIs. These studies also facilitate pilot testing of new interventions to improve service delivery.
The TRUST/RV368 cohort study reflects the dual MHRP mission in Nigeria to promote HIV prevention and treatment as well as HIV research. These prospective observational sister studies enrolled over 2700 men who have sex with men (MSM), transgender women (TGW) and other sexual and gender minorities in Nigeria. The University of Maryland School of Medicine and the Institute of Human Virology Nigeria conducted the TRUST study in Abuja, the seat of government in Central Nigeria, and MHRP/DoD Nigeria conducted RV368 in Lagos, the country’s largest city and center of commerce in Southwest Nigeria. The MHRP-supported Defense Reference Laboratory provided centralized laboratory testing for STIs at both clinical research sites.
The studies employed respondent driven sampling for recruitment, a method that recruits via "coupons" distributed by study participants to potentially eligible individuals within their social network. This is an efficient means of accessing participant populations that are marginalized, stigmatized, and may be missed by other recruitment methods. The study took place at pre-existing community health centers that were run by local non-governmental organizations, supported by PEPFAR, and provided comprehensive HIV treatment and prevention services tailored to MSM, TGW, and other sexual and gender minorities. Study participants received enhanced counseling, peer support and advanced STI diagnostics, including PCR-based testing of three anatomic sites every three months. Participants also completed in-depth interviews to evaluate behaviors, healthcare engagement, stigma and other parameters. Participants living with HIV were offered antiretroviral therapy and monitored for immunologic and viral response.
Researchers found an extraordinarily high burden of HIV and other STIs among participants in this study. About half of participants had HIV upon enrollment into the cohort, and new infections were diagnosed at a rate of over 11 cases per 100 person-years. High prevalence and incidence of Chlamydia and gonorrhea were also observed, and infection with human papillomavirus were common. Some bacterial STIs carried markers of antimicrobial resistance that could complicate treatment strategies.
Almost 10% of participants who were newly diagnosed with HIV had evidence of transmitted drug resistance. Participants described how prior stigma experiences often generated perceptions of feeling unsafe, which decreased willingness to seek services at general health facilities. Participants who experienced stigma related to their same-sex sexual practices were more likely to have STIs than were participants without such experiences. An unmet need for mental health services was observed that, if addressed, could reduce STI and HIV acquisition.
MHRP researchers characterized circulating HIV-1 subtypes among the RV368 cohort and found a novel circulating recombinant form of the virus that represents an interplay of the G subtype predominant in West Africa and the B subtype more common in the Western hemisphere. These findings provide evidence that the West African epidemic is interacting with the Western epidemic, which has implications for vaccine design.
U.S. Military HIV Natural History Study
MHRP collaborates with the Infectious Disease Clinical Research Program (IDCRP) at the Uniformed Services University on analyses of data and specimens from the U.S. Military HIV Natural History Study (NHS). Since 1986, the NHS has enrolled over 6400 active duty personnel and DoD medical beneficiaries who are living with HIV at five military medical centers. The military healthcare system enables rapid care linkage and comprehensive collection of laboratory, pharmacy, and clinical data. NHS participants undergo collection of PBMCs, plasma, and serum approximately every six months for future research, providing unparalleled long-term sampling and clinical data for the evaluation of HIV-related clinical outcomes.
Collaboration on the NHS has provided critical information about the impact of HIV on active duty service members and military beneficiaries, documenting substantial improvement in clinical outcomes over the decades. Non-AIDS-defining infections are the most common reason for hospitalization in this relatively young population with universal access to healthcare.
This prospective observational study of HIV and other STIs is designed to provide one unified protocol and set of data collection instruments for deployment across multiple sites in diverse regions of world. It facilitates preparedness for future HIV and STI prevention studies by estimating HIV and STI incidence in populations at risk, tracking the evolution of risk and healthcare-seeking behaviors, building site capacity, evaluating recruitment and retention capacity at participating sites, and maintaining relationships with communities affected by HIV and other STIs.
The study enrolls participants who are at risk for HIV and follow them with visits every 12 weeks to evaluate for HIV and other STIs. Participants are also provided HIV home testing kits for use between scheduled visits. Participants who are diagnosed with HIV are referred for immediate initiation of antiretroviral therapy and followed for viral and immune response to therapy. Participants who achieve viral suppression after early treatment remain engaged for up to five years, serving as a source population for potential recruitment into future interventional studies, including studies of novel strategies induce durable viral suppression. The first sites to begin enrollment into MOCHI are in Uganda and Kenya.
In collaboration with the Institute for HIV Research at the University Bonn, the BRAHMS study enrolled over 1,000 men who were behaviorally vulnerable to HIV at ten German clinics that cater to gender and sexual minority populations. Enrolled participants received risk reduction counseling and underwent testing for HIV and other STIs every three months for up to 12 months in order to evaluate the incidence of HIV and determine the feasibility of conducting an HIV vaccine efficacy trial in a population that, like the U.S. military, is predominantly affected by a subtype B epidemic. BRAHMS is the largest systematic epidemiologic study of STIs in Germany and includes testing for a variety of common and uncommon infections, including chlamydia, gonorrhea, syphilis, Mycoplasma genitalium, Trichomonas vaginalis, and viral hepatitides.
Contemporary Epidemiology of HIV in Jordan
MHRP is collaborating with the Emerging Infectious Diseases Branch at WRAIR to conduct the first observational HIV study to take place in the Kingdom of Jordan. RV505 seeks to understand the evolving HIV epidemic in the country, gathering information on HIV risk factors, outcomes, genotypes and drug resistance profiles. It includes a cross-sectional survey with standardized bio-behavioral and viral characterization of Jordanians and Syrian refugees living with HIV in Jordan as well as a period of prospective, active HIV surveillance. The findings of this study will inform clinical care and public health practice in the region.