Man Charurat

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Background Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria. Methods and Findings We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p<0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml3) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100–200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p≤0.001) were more likely to be adherent. Conclusions These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.

Uptake of treatment as prevention for HIV and continuum of care among HIV-positive men who have sex with men in Nigeria.

Background:Experimental evidence has shown that treatment of HIV infection with antiretroviral therapy (ART) prevents heterosexual transmission of HIV to an uninfected partner. However, the “real-world” application of this strategy to key populations such as men who have sex with men (MSM) has been limited. We report findings on acceptability of a treatment as prevention (TasP) strategy among HIV-infected MSM at a Trusted Community Center providing comprehensive HIV prevention and treatment services to MSM in Abuja, Nigeria. Methods:Using respondent-driven sampling (RDS), MSM who were 16 years and older and have engaged in either receptive or insertive anal intercourse within the previous 12 months were recruited into a prospective combination HIV prevention and treatment study (TRUST). Two weeks after enrollment, HIV testing and counseling was conducted. At each 3-month follow-up visits, HIV-infected individuals underwent clinical and laboratory evaluation, including CD4 count, plasma HIV viral load, immediate 3 weekly sessions of ART preparation, and then ART initiation per TasP strategy irrespective of CD4 count. Reasons for not engaging in pre-TasP preparation and TasP were documented. Characteristics associated with TasP engagement and loss to follow-up (LTFU) were determined using logistic and Cox regression, respectively. Results:Of 186 HIV-positive MSM enrolled, 58 (31.2%) were on ART at the time of recruitment, whereas 128 (68.8%) were ART-naive and provided opportunity for engaging TasP. Of these, 70 (54.7%) engaged in TasP. Compared with MSM who did not engage in TasP, those who engaged had significantly lower mean CD4 count (P = 0.001), were more likely to be Christian (P = 0.01), and had disclosed being MSM to family (P = 0.02) or health care providers (P = 0.02). In multivariate models, disclosure of being MSM to health care providers remained significantly associated with uptake of TasP. Among individuals engaged in TasP, 10% were LTFU in care at 18 months since enrollment. Being engaged in TasP (relative hazards = 0.08, P < 0.001) and on ART (relative hazards = 0.17, P < 0.001) were associated with decreased risk of LTFU. Conclusions:Although there was high acceptance of HIV testing and low LTFU among individuals who were already on ART or engaged in TasP, a higher than expected proportion did not engage in TasP, suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population.

Immuno-virologic outcomes and immuno-virologic discordance among adults alive and on anti-retroviral therapy at 12 months in Nigeria

BackgroundPredictors of immuno-virologic outcomes and discordance and their associations with clinical, demographic, socio-economic and behavioral risk factors are not well described in Nigeria since HIV viral load testing is not routinely offered in public HIV treatment programs.MethodsThe HACART study was a multi-center observational clinic-based cohort study of 2585 adults who started HAART between April 2008 and February 2009. A total of 628 patients were randomly selected at 12 months for immuno-virologic analyses.ResultsVirologic suppression rate (<400 copies/ml) was 76.7%, immunologic recovery rate (CD4 change from baseline ≥50 cells/mm3) was 77.4% and immuno-virologic discordance rate was 33%. In multivariate logistic regression, virologic failure was associated with age <30 years (OR 1.79; 95% CI: 1.17-2.67, p=0.03), anemia (Hemoglobin < 10 g/dl) (OR 1.71; 95% CI: 1.22-2.61, p=0.03), poor adherence (OR 3.82; 95% CI: 2.17-5.97, p=0.001), and post-secondary education (OR 0.60; 95% CI: 0.30-0.86, p=0.02). Immunologic failure was associated with male gender (OR 1.46; 95% CI: 1.04-2.45, p=0.04), and age <30 years (OR 1.50; 95% CI: 1.11-2.39, p=0.03). Virologic failure with immunologic success (VL-/CD4+) was associated with anemia (OR 1.80; 95% CI: 1.13-2.88, p=0.03), poor adherence (OR 3.90; 95% CI: 1.92-8.24, p=0.001), and post-secondary education (OR 0.40; 95% CI: 0.22-0.68, p=0.005).ConclusionsAlthough favorable immuno-virologic outcomes could be achieved in this large ART program, immuno-virologic discordance was observed in a third of the patients. Focusing on intensified treatment preparation and adherence, young patients, males, persons with low educational status and most importantly baseline anemia assessment and management may help address predictors of poor immuno-virologic outcomes, and improve overall HIV program impact. Viral load testing in addition to the CD4 testing should be considered to identify, characterize and address negative immuno-virologic outcomes and discordance.

Social determinants of mixed feeding behavior among HIV-infected mothers in Jos, Nigeria

Abstract Mixed feeding confers excess risk of mother-to-child transmission (MTCT) of HIV compared with exclusive breastfeeding and exclusive formula feeding. We undertook a qualitative and quantitative cross-sectional survey to identify the social determinants of mixed feeding among a subset of the 469 HIV-infected women enrolled in a MTCT prevention program in Jos, Nigeria. Formula was provided free-of-cost. Of the 91 participants, 68 (75%) exclusively formula fed, 7 (8%) exclusively breastfed, and 16 (18%) practiced mixed feeding. Of the mixed feeding women, seven primarily formula fed and nine primarily breastfed. Women who primarily formula fed described family pressure as the reason for mixed feeding, while women who primarily breastfed reported insufficient breast milk. In a multivariate analysis, lack of partner support of the feeding decision predicted mixed feeding behavior (OR: 4.2; 95% CI: 1.2–14.9; p=0.03). Disclosure of HIV status was significantly correlated (p<0.001) with partner support. HIV prevention interventions aimed at reducing mixed feeding should encourage supportive partner relationships that facilitate disclosure of HIV status. Attention should also be made to the differing pressures faced by women attempting to exclusively breast feed and exclusively formula feed.

Effect of age on immunological response in the first year of antiretroviral therapy in HIV-1-infected adults in West Africa

Objective:To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context. Methods:The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen. Results:The total number of patients included was 24 107, contributing for 50 893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/&mgr;l [interquartile range (IQR) 61–235]; median CD4 cell count reached 310 cells/&mgr;l (IQR 204–443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th–90th percentiles = 26.5–50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/&mgr;l on average [95% confidence interval (CI) 2–43] compared to patients at least 50 years. Conclusion:Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.

Timing and determinants of mother-to-child transmission of HIV in Nigeria.

To characterize the timing and determinants of mother‐to‐child transmission (MTCT) of HIV among mothers receiving single‐dose nevirapine to prevent MTCT in Nigeria.

HIV counseling and testing and access-to-care needs of populations most-at-risk for HIV in Nigeria.

Abstract Mobile HIV counseling and testing (mHCT) is an effective tool to access hard-to-reach most-at-risk populations (MARPs), but identifying which populations are not accessing services is often a challenge. We compared correlates of human immunodeficiency virus (HIV) infection and awareness of HIV care services among populations tested through mHCT and at testing facilities in Nigeria. Participants in a cross-sectional study completed a questionnaire and HCT between May 2005 and March 2010. Of 27,586 total participants, 26.7% had been previously tested for HIV; among mHCT clients, 14.7% had previously been tested. HIV prevalence ranged from 6.6% among those tested through a facility to 50.4% among brothel-based sex workers tested by mHCT. Among mHCT participants aged 18–24, women were nine times more likely to be infected than men. Women aged 18–24 were also less likely than their male counterparts to know that there were medicines available to treat HIV (63.2 vs. 68.1%; p=0.03). After controlling for gender, age, and other risk factors, those with current genital ulcer disease were more likely to be HIV-infected (ORmHCT=1.65, 1.31–2.09; ORfacility=1.71, 1.37–2.14), while those previously tested were less likely to be HIV-infected (ORmHCT=0.75, 0.64–0.88; ORfacility=0.27, 0.24–0.31). There is an urgent need to promote strategies to identify those who are HIV-infected within MARPs, particularly young women, and to educate and inform them about availability of HIV testing and care services. mHCT, ideally coupled with sexually transmitted infection management, may help to ensure that MARPs access HIV prevention support, and if infected, access care, and treatment.

Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy

Background:In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Methods:Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. Results:One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). Conclusions:At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

Characterization of Acute HIV-1 Infection in High-Risk Nigerian Populations

BACKGROUND Acute phase of human immunodeficiency virus (HIV) infection (AHI) may account for a significant proportion of HIV-1 transmission. We identified and characterized individuals in Nigeria with AHI. METHODS Individuals were tested using a combination of rapid HIV testing in mobile units and laboratory-based specimen pooling for nucleic acid amplification testing. Genome sequences were characterized. A linear segmented regression model was fit to serial viral load (VL) measurements to characterize early VL profiles. RESULTS Sixteen AHIs were identified from 28 655 persons screened. Specimens were genotyped: 7 (43.8%) were CRF02_AG, 6 (37.5%) were subtype G, 1 (6.3%) was CRF06_cpx, and 2 (12.5%) were unique recombinant forms. No antiretroviral resistance mutations were detected. The mean duration of high VL burden from peak to nadir was 76 days (95% confidence interval [CI], 58-93 days), and the mean rate of viremic control was -0.66 log(10) VL per month. The mean VL at set-point was 4.5 log(10) copies/mL (95% CI, 3.9-5.1 log(10) copies/mL). CONCLUSIONS This study is the first to characterize AHI among Nigerians identified as HIV infected before seroconversion who would be otherwise missed by conventional HIV testing. Infections by HIV subtypes in Nigeria exhibit long periods of high viral burden, which can contribute to increased transmissibility.

Comparison of HIV oral fluid and plasma antibody results during early infection in a longitudinal Nigerian cohort.

BACKGROUND Oral fluid (OF) testing is a less-invasive alternative to blood-based testing for HIV. The performance of HIV OF tests has not been extensively evaluated in serially collected paired specimens from seroconverters. OBJECTIVE To compare paired OF and plasma test performance in a cohort of HIV-1 seroconverters from Nigeria. STUDY DESIGN Paired plasma and OF specimens from 14 seroconverters collected during 24 months of longitudinal follow up were included in the study. Plasma and OF were tested using Avioq HIV-1 Microelisa System, and first reactivity in plasma and OF specimens was compared. OF specimens reactive by Avioq were subsequently tested by OraSure HIV-1 Western blot. Genetic Systems HIV-1 Western blot was also performed on the corresponding plasma of the first 2 Avioq-OF positive time-points. RESULTS Of the 14 seroconverters, 5 (35.7%) had concordant results between plasma and OF for all time points tested, whereas 9 (64.3%) showed reactivity on plasma before OF specimens early in infection. The median delay between plasma and OF reactivity was 29 days (range: 0 day-20 months) (p<0.0039); the median overall delay for OF compared to RNA testing was 69.5 days. Delayed antibody response with OF was observed in both males and females regardless of viral load or HIV subtypes. CONCLUSIONS Results demonstrate decreased sensitivity of OF testing compared to blood-based testing with specimens obtained early after HIV infection. Programs that utilize OF testing in populations with increased risk of incident HIV infection should understand these limitations of OF testing.