AITRP research training activities are based on country need as Nigeria is ranked number two in the world for HIV/AIDS, number five for tuberculosis, and number 159 of 177 (bottom 30) in Human Development Index and for the opportunity to advance research training for immediate and significant impact. The scientific focus of research training of the UM-IHV AITRP is in the areas of Optimization of Public Health Scale-up (Implementation Science), Treatment ARV Response Resistance and Safety, Tuberculosis and HIV/AIDS, HIV Associated Malignancies, Neurological Mental Health and Behavioral Research, Prevention of Mother to Child Transmission and Pediatric HIV, and Laboratory Research.
The scale-up of ART throughout Nigeria has transformed the landscape of patient management and HIV care service delivery, which is resource-intensive and requires significant patient commitment. Non-adherence to antiretroviral medications and default from care contribute to poorer health outcomes and wastage of limited resources. The key challenge for Nigeria is to build local capacity to study health systems’ quality and effectiveness and to measure the impact of interventions such as task shifting, mobile services and community-based models of health care on program outcomes.
Different first-line ARV regimens may contribute to varying responses to treatment and emergence of drug resistance. Treatment failure is emerging as a major challenge. Poor adherence is associated with the emergence of extensive drug resistance. The key challenge for Nigeria is to strengthen the local capacity in using research methodologies to characterize the intermediate-term and long-term outcomes of ART. For example, given differences in tolerability of NRTI and high rates of mutation, what are the best treatment and monitoring strategies that are feasible in a resource limited setting? Additionally, are there virological factors linked to the complex distribution of HIV-1 subtypes in Nigeria that could impact rates and patterns of drug resistance? Within these constraints, what is the impact of treatment on clinical outcomes such as opportunistic infections, AIDS-related illnesses, and mortality?
TB, caused by Mycobacterium tuberculosis, remains a major public health problem in Nigeria especially in the context of the HIV epidemic and the emergence of drug-resistance. There is growing evidence that some of the genetic strain variation can have phenotypic, clinical implications and may contribute to the variable clinical presentation of disease. Within the context of program implementation, lack of linkages for improving isoniazid (INH) prophylaxis and intensive phase treatment for drug resistance exists as supported by a UM-IHV AITRP trainee’s analysis of barriers to effective integration of TB and HIV services in Nigeria and the impact of a balkanized diagnostic and delivery system on uptake into a pilot isoniazid prophylaxis intervention. TB infection caused by Mycobacterium bovis can be detected in 15% of cases pointing to public health concerns about the consumption of unpasteurized dairy products among persons with immune compromise. Strengthening the local capacity’s ability to conduct TB-HIV research is a key challenge so Nigeria can address deficiencies in case detection, TB strain characterization, and drug resistance patterns in relation to HIV infection and high-risk populations.
With the scale-up of treatment access programs, more people in Nigeria are now living with HIV, but at increased risk of cancer, including cervical cancer, which is a leading cause of death among women with cancer in Nigeria. The high frequency of advanced untreatable cervical cancer associated with HIV infection emphasizes a lost prevention opportunity. For the next five years, the key challenge for Nigeria is to build local capacity in HIV-related cancer epidemiology and prevention, particularly cervical cancer, and local ability to investigate treatment of HIV-associated malignancies.
A major challenge in the scale up of HIV therapy is to maintain treatment adherence >95% in order to avoid emergence of drug resistance. The contributors to non-adherence are complex and include individual and societal factors. As a neurotrophic virus, HIV has direct effects on neurocognitive function that affects daily function including treatment adherence. Similar to studies of Saktor et al. in Uganda32, an UM-IHV AITRP supported training found that up to 20% of treatment-naïve patients have objective evidence of neurocognitive impairment based on assessment with the International HIV Dementia Scale and presence of dementia is inversely correlated with CD4 count as shown in the study. The key challenge for Nigeria is to integrate capacity for behavioral and neuropsychological research into multidisciplinary activities that address the long-term effects of HIV infection and to investigate the impact of ART on reversing these effects.
With an infant mortality rate of 93 per 1000 births, Nigeria ranks 13th in the world. Each year up to 125,000 infants acquire HIV among the 315,000 to 625,000 children born annually to HIV infected mothers reflecting the low uptake and retention in PMTCT services. The contributors to infant mortality include poor pre- and post-natal service access, malnutrition, unsanitary water, and malaria among others. These challenges are amplified in the context of HIV. Unfortunately, little is known about barriers to pediatric adherence in the context of expanded treatment access. The key challenge for Nigeria is to strengthen the capacity of local investigators to conduct integrated and multidisciplinary studies that contextualize PMTCT and pediatric HIV in the larger challenges of maternal and infant health and health systems.
Unlike Southern Africa where a single virus subtype C predominates perhaps related to adaptive motifs in the NFKB binding domain, the molecular epidemiology of HIV in Nigeria involves a complex pattern of circulating recombinants and subtypes that are uniquely indigenous to West Africa with CRF02_AG predominating followed by subtype G with the remaining 10 to 15 % being unique and other recombinant forms. There is a growing body of laboratory research needed to support treatment response by virus subtype efficiency of transmission, neurological manifestations by subtype, HIV-associated malignancy (understanding of host, viral and cellular factors), and potential therapeutic effects of some traditional remedies. The key challenge for Nigeria, now that substantial laboratory research capacity has been built on the PEPFAR platform, is to broaden the capacity of laboratory scientists to engage in multidisciplinary studies that inform clinical, epidemiological, and pathogenesis research.