Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices.

ObjectivesTo analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe.MethodsPatients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir.ResultsGenotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3–5.1) and 2.6 years (IQR, 1.6–4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728–208 920 copies/mL) and 201 cells/mm3 (IQR, 49–333 cells/mm3). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years (P = .003) and CD4 cell count <200 cells/mm3 (P = .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69–13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months.ConclusionsThe prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

Objective To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. Methods We analyzed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/L and which is confirmed by a fasting blood sugar higher than 7.0 mmol/L to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95%CI). Results Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR:31–43) years. Median baseline CD4 count was 197 (IQR: 95–337) cells/mm3. The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR:2.1–7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95%CI: 2.1 – 3.6) per 1000 person-years of follow up. Exposure to PIs was associated with T2DM (HR: 1.80, 95%CI: 1.04–3.09). In the multivariable analysis, obesity (BMI>30kg/m2) (aHR=2.26, 95%CI: 1.17–4.36), age >40yrs (aHR=2.16, 95%CI: 1.22–3.83) and male gender, (aHR=2.13, 95%CI: 1.22–3.72) were independently associated with the risk of T2DM. HIV related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. Conclusion Even though the incidence of T2DM in this HIV cohort was lower than has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early detection and treatment of chronic diseases especially among the elderly and obese.

The extremely high prevalence of HIV/AIDS in sub-Saharan Africa and limitations of current antiretroviral medicines demand new tools to optimize therapy such as pharmacogenomics for person-toperson variations. African populations exhibit greater genetic diversity than other world populations, thus making it difficult to extrapolate findings from one population to another. Nevirapine, an antiretroviral medicine, displays large plasma concentration variability which adversely impacts therapeutic virological response. This study, therefore, aimed to identify sources of variability in nevirapine pharmacokinetics and pharmacodynamics, focusing on genetic variation in CYP2B6 and CYP1A2. Using a cross-sectional study design, 118 HIV-infected adult Zimbabwean patients on nevirapine-containing highly active antiretroviral therapy (HAART) were characterized for three key functional single nucleotide polymorphisms (SNPs), CYP2B6 c.516G>T (rs3745274), CYP2B6 c.983T>C (rs28399499), and CYP1A2 g.-163C>A (rs762551). We investigated whether genotypes at these loci were associated with nevirapine plasma concentration, a therapeutic biomarker, and CD4 cell count, a biomarker of disease progression. CYP2B6 and CYP1A2 were chosen as the candidate genes based on reports in literature, as well as their prominence in the metabolism of efavirenz, a drug in the same class with nevirapine. Nevirapine plasma concentration was determined using LC-MS/MS. The mean nevirapine concentration for CYP2B6 c.516T/T genotype differed significantly from that of 516G/G ( p < 0.001) and 516G/T ( p < 0.01) genotypes, respectively. There were also significant differences in mean nevirapine concentration between CYP2B6 c.983T > C genotypes ( p = 0.04). Importantly, the CYP1A2 g.-163C>A SNP was significantly associated with the pharmacodynamics endpoint, the CD4 cell count ( p = 0.012). Variant allele frequencies for the three SNPs observed in this Zimbabwean group were similar to other African population groups but different to observations among Caucasian and Asian populations. We conclude that CYP2B6 c.516G>T and CYP2B6 c.983T>C could be important sources of nevirapine pharmacokinetic variability that could be considered for dosage optimization, while CYP1A2 g.-163C>A seems to be associated with HIV disease progression. These inter-and intra-population pharmacokinetic and pharmacodynamics differences suggest that a single prescribed dosage may not be appropriate for the treatment of disease. Further research into a personalized nevirapine regimen is required.

BackgroundData on long-term outcomes of patients receiving antiretroviral therapy (ART) in sub-Saharan Africa are few. We describe outcomes of patients commenced on ART at Newlands Clinic between 2004 and 2006 after ≥10 years of comprehensive care including, psychosocial, adherence and food support.MethodsIn this retrospective cohort study, patient data from an electronic medical record collected during routine care were analysed. We describe baseline characteristics, virological and clinical outcomes, attrition rates, and treatment adverse effects until November 2016. We defined virological suppression as viral load <50 copies/ml and virological failure as >1000 copies/ml after ≥6 months of ART.ResultsWe analysed data for 605 patients (67% female) who commenced ART, and were followed-up for 5819 person-years (median: 10.7 years, IQR: 10.1–11.4). Median age at ART initiation was 34 years (IQR: 17–42). Pre-ART, 129 (21.3%) patients had history of pulmonary tuberculosis (PTB). In care, 66 (11%) developed PTB, and 24 (4%) developed extrapulmonary tuberculosis. 385 (63.6%) patients experienced ≥1 adverse event, the most frequent being stavudine-induced peripheral neuropathy (n = 252, 41.7%). At database closure on 14 November 2016, 474 (78.3%) patients were still in care, 428 (90.3%) being virologically suppressed, and 21 (4.4%) failing. While 483 (79.8%) remained on first line, 122 (20.2%) were switched to second line ART. Fifty-nine patients (9.8%) were transferred to other ART facilities, 45 (7.4%) were lost to follow-up, 25 (4.1%) died, and two stopped ART.ConclusionComprehensive HIV care can result in low mortality, high retention in care and virologic suppression rates in resource limited settings.