Critical insights that have helped to shape HIV/AIDS program implementation and care and treatment have come from public health evaluations and research projects conducted in collaboration with faculty from the Institute of Human Virology in Baltimore and Nigeria. The Fogarty sponsored AIDS International Training and Research Program (AITRP) grant has provided one mechanism to support engagement of IHV Nigeria faculty and staff as well as partners from IHV-Nigeria’s network of academic and research institution partners.
The REACH Study with research funding from CDC was conducted to develop a non-subtype B acute HIV infection cohort by creening most-at-risk populations (MARPs) through mobile HIV counseling and testing (mHCT) as well as evaluate the performance of the Nigerian Rapid Test Algorithm. This project taught the IHV-Nigeria HCT program that mHCT is a valuable tool for effectively reaching high risk populations and identified challenges for promoting access to care and treatement. Of 9371 individuals reached by mHCT between May 2005 and July 2008, 89.1% had never been tested previously. Prevalence in populations accessed ranged from 8.1% among motorcycle/taxi drivers to 52.9% in brothel-based sex workers. Increased seroprevalence was associated with younger females. Current symptoms for STIs were reported by 11.1% of the population, higher for women (OR=1.9, 1.8-2.1), and were associated with HIV infection (OR=2.2, 1.9-2.4). Awareness of HIV services and the benefits of antiretrovirals on prolonging survival were lower for MARPs (59.6% and 55.1%, respectively), especially among females (57.8% and 52.7%) compared to clients tested in health facilities (68.5% and 85.1%). A particularly disturbing finding in this study is the rising rate of HIV infection in contrast to a declining national prevalence. The use of mHCT informed by linkage with community information and prevalence data can effectively identify areas of high HIV prevalence density where services such as diagnosis, prevention, antiretroviral treatment, and care efforts can be focused. IHV-Nigeria is expanding coverage for prevention among MARPs by supporting special HIV intervention programs such as peer education, early treatment for sexually-transmitted infections, partner notifications, and condom distribution with local non-governmental organizations.
Mortality rate of 93 per 1000 births, Nigeria ranks 13th in the world. Each year 63,000 - 125,000 infants acquired 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. Current evidence indicates that 70-90% of women in the Nigerian PMTCT program opt for replacement feeding but a significant proportion convert to mixed feeding which is shown to be associated with increased MTCT as well as heighten mortality. An additional factor is malnutrition and HIV’s impact on the nutritional status of infants born to HIV infected mothers including those infected children on ART. Recent programmatic findings point to a high incidence of HIV infection during pregnancy that could contribute disproportionately to MTCT. In a study evaluating feeding patterns in the Government of Nigeria PMTCT program with funding from the Bill and Melinda Gates Foundation, high rates of infant infection are associated with mixed feeding and a heighten risk for diarrheal deaths in infants exposed to unclean water. Based on these finding the care and support team for the PEPFAR program are targeting HIV infected mothers for safe water supplies.
Different first-line ARV regimens may contribute to varying responses to treatment and emergence of drug resistance. A project funded through a Fogarty training grant training project evaluated emergence of treatment resistance. In this study among patients started on ART, 96% were initiated on one of the 6 defined first-line regimens approved by the Nigerian national guidelines [35% on d4T, 49% on ZDV, and 16% on TDF; 85% on NVP and 15% on EFV]. Although the mean increase in CD4 T cell count at 6, 12 and 18 months for each of the six regimens was equivalent across different first-line regimens with overall mean increase at 6 months of 134 cells/ul, the frequency of substitution between first-line agents was three times higher for d4T-based regimens compared with AZT- and TDF-based regimens. Substitutions of AZT- and TDF-based regimens tended to occur early after ARV initiation whereas d4T substitutions occurred later reflecting the impact of toxicity. Treatment failure is emerging as a major challenge. Poor adherence is associated with the emergence of extensive drug resistance, where for example, among a cohort of patients suspected to have treatment failure based on clinical observation, 30% were found to have more than four drug resistant mutations that would eliminate most of the WHO-recommended second-line treatment. The finding that duration on therapy correlated with the number of NRTI drug resistant mutations reinforces emerging evidence that WHO immunological criteria have poor sensitivity for predicting treatment failure before extensive drug resistance emerges. As part of this analysis it was found that Tenofovir-based regimens are associated with fewer NRTI resistance mutations.
A major challenge in the scale up of HIV therapy is to maintain treatment adherence >95% in order avoid emergence of drug resistance. The contributors to non-adherence are complex and include individual and societal factors. Although some published reports point to good adherence and treatment outcome in sub-Saharan Africa compared to developed countries, most of the published data is from supervised cohorts in urban centers. Such evidence from treatment program integrated into routine secondary and primary centers in rural areas is still scarce. In Nigeria, analysis of pharmacy refill for non-adherence to ARVs at 6 urban centers in Nigeria found that risk of non-adherence to ARV is associated with younger age, higher CD4 at ART initiation, d4T-based first-line regimen, and longer travel time to the clinic while disclosure of HIV status to spouse or a family member reduced the risk of non-adherence. Among Muslim women in northern Nigeria cultural factors such as stigma and lack of family support negatively impact treatment access. Similarly former IHV-Nigeria Medical Director, Dr. Habib, showed that the Ramadan fast negatively impacted adherence. As a neurotrophic virus, HIV has direct effects on neurocognitive function that affects daily function including treatment adherence. A study supported by the UM-IHV AITRP conducted by IHV-Nigeria staff 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. In addition to the direct effects of HIV on neurocognitive function, high rates of depression and high rates of alcohol abuse, particularly among men have been found in a study supported through the UM-IHV AITRP. Of particular note is the finding among patients receiving ART a low pharmacy refill rate (< 95%) is significantly associated with an elevated Center for Epidemiological Studies Depression Scale [CES-D > 16 (p=0.004) and a CES-D > 21 (p<0.001)]. These data emphasize the importance of integrating mental health services into the care and support structure of patients engaged in treatment scale up.