Implementation and Dissemination Science Research
The transmission of HIV from HIV-positive mother to her baby during pregnancy, labor and delivery or breastfeeding rate can be reduced from 15%-45% to below 5% with effective interventions. Context-appropriate, culturally-acceptable, and sustainable interventions are needed, especially in resource-limited settings. Nigeria is one of 22 Global Priority countries that contribute the most to PMTCT gaps worldwide. Major issues in Nigeria’s PMTCT program include access to, and coverage of essential services and long-term retention of mothers and babies in care.
The INSPIRE MoMent study (PI Nadia Sam-Agudu) investigates the impact of a structured, supervised peer counseling intervention on uptake of PMTCT services and retention in care among HIV-infected mothers and HIV-exposed babies in rural North-Central Nigeria. This WHO and Canadian government-supported study involves 20 Primary Healthcare Centers, and has completed enrollment; follow-up is expected to be completed in March 2017. Findings so far demonstrate that the Mentor Mother intervention is highly acceptable in study communities, and that acceptability of this intervention is high regardless of religious affiliation (Christian or Muslim) of the target population. Data analysis with respect to Early Infant Diagnosis uptake and 6 month retention will be completed in the next 6 to 12 months.
Studies on the emerging crisis of adult drug resistance to antiretroviral drugs (ARV) in Nigeria, continues to be a focus of our Division to help guide policy. We conducted an international multi-centre retrospective study of individuals undergoing genotypic resistance testing following virological failure with a first-line ART regimen containing tenofovir plus a cytosine analogue (lamivudine/emtricitabine) plus a non-nucleotide reverse transcriptase inhibitor (NNRTI) - efavirenz/nevirapine. Patient level meta-analysis and multiple logistic regression were used to identify covariates associated with drug resistance.
Prevalence of tenofovir resistance amongst 1926 patients in 36 countries with treatment failure was highest in LMIC regions, approaching 60% across sub Saharan Africa. In all geographic regions, pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance: OR 1.50 (1.27-1.77 for CD4 count <100 cells/mm3). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance [OR 1.48 (1.20 - 1.82)] across regions. Amongst individuals with with tenofovir resistance, 82.6% had cytosine analogue resistance (M184V/I mutation), 77.6% had major NNRTI resistance, and 65.2% had both. In Europe, HIV-1 subtype C infection was associated with tenofovir resistance at virologic failure compared to other subtypes circulating in Africa [OR 2.44 (1.66-3.59)].
We performed an observational cohort study of 100 children (0-12 years) starting ART without previous PMTCT exposure in Lagos, Nigeria. Stored plasma samples from selected time points were assayed retrospectively for HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >=1000 copies per milliliter at month 24 were sequenced. Sixteen of 82 (19.5%) of HIV-infected children had pre-treatment HIVDR, all 16 (19.5%) children had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, and 6 (7.3%) also had nucleoside reverse transcriptase inhibitor (NRTI) mutations.
No protease inhibitor (PI) mutations were detected. HIVDR was present in a fifth of PMTCT-unexposed Nigerian children prior to treatment initiation. This high and increasing prevalence of HIVDR in a population without previous PMTCT-exposure, a risk factor for HIVDR, underscores the importance of PI-based regimens in young children. Overcoming practical barriers to implement PI-based regimens should receive priority. Implementation of population-based pediatric HIVDR surveillance is crucial in order to ensure optimal treatment for HIV-infected children in resource-constraint settings.