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Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

Laboratory reference ranges used for clinical care and clinical trials in various laboratories in Zimbabwe were derived from textbooks and research studies conducted more than ten years ago. Periodic verification of these ranges is essential to track changes over time. The purpose of this study was to establish hematology and chemistry laboratory reference ranges using more rigorous methods.A community-based cross-sectional study was carried out in Harare, Chitungwiza, and Mutoko. A multistage sampling technique was used. Samples were transported from the field for analysis at the ISO15189 certified University of Zimbabwe-University of California San Francisco Central Research Laboratory. Hematology and clinical chemistry reference ranges lower and upper reference limits were estimated at the 2.5th and 97.5th percentiles respectively.A total of 769 adults (54% males) aged 18 to 55 years were included in the analysis. Median age was 28 [IQR: 23-35] years. Males had significantly higher red cell counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin compared to females. Females had higher white cell counts, platelets, absolute neutrophil counts, and absolute lymphocyte counts compared to males. There were no gender differences in eosinophils, monocytes, and absolute basophil count. Males had significantly higher levels of urea, sodium, potassium, calcium, creatinine, amylase, total protein, albumin and liver enzymes levels compared to females. Females had higher cholesterol and lipase compared with males. There are notable differences in the white cell counts, neutrophils, cholesterol, and creatinine kinase when compared with the currently used reference ranges.Data from this study provides new country specific reference ranges which should be immediately adopted for routine clinical care and accurate monitoring of adverse events in research studies.

OBJECTIVE:The association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain. DESIGN:Nested case-control study (n = 332) within ACTG PEARLS trial of three ART regimens among 1571 HIV-infected, treatment-naïve adults in 9 countries. We compared cases (participants with incident TB diagnosed by 96 weeks) to a random sample of controls (participants who did not develop TB, stratified by country and treatment arm). METHODS:We measured pre-ART C-reactive protein (CRP), EndoCab IgM, ferritin, interferon gamma (IFN-γ), interleukin 6 (IL-6), interferon gamma-inducible protein 10 (IP-10), lipopolysaccharide (LPS), soluble CD14 (sCD14), tumor necrosis factor alpha (TNF-α), and CD4/DR+/38+ and CD8/DR+/38+ T cells. Markers were defined according to established cutoff definitions when available, 75th percentile of measured values when not, and detectable versus undetectable for LPS. Using logistic regression, we measured associations between biomarkers and incident TB, adjusting for age, sex, study site, treatment arm, baseline CD4 and log10 viral load. We assessed the discriminatory value of biomarkers using receiver operating characteristic (ROC) analysis. RESULTS:Seventy-seven persons (4.9%) developed incident TB during follow-up. Elevated baseline CRP (aOR 3.25, 95% CI: 1.55-6.81) and IP-10 (aOR 1.89, 95% CI: 1.05-3.39), detectable plasma LPS (aOR 2.39, 95% CI: 1.13-5.06), and the established TB risk factors anemia and hypoalbuminemia were independently associated with incident TB. In ROC analysis, CRP, albumin, and LPS improved discrimination only modestly for TB risk when added to baseline routine patient characteristics including CD4 count, body mass index, and prior TB. CONCLUSION:Incident TB occurs commonly after ART initiation. Although associated with higher post-ART TB risk, baseline CRP, IP-10, and LPS add limited value to routine patient characteristics in discriminating who develops active TB. Besides determining ideal cutoffs for these biomarkers, additional biomarkers should be sought that predict TB disease in ART initiators.

OBJECTIVE:Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low-income African countries. METHODS: SETTING:HIV clinics in Uganda and Zimbabwe. DESIGN:Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. OUTCOME MEASURES:Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without. RESULTS:A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV-1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis. CONCLUSIONS:Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.

Abstract Background While barriers to uptake of antenatal care (ANC) among pregnant women have been explored, much less is known about how integrating prevention of mother-to-child transmission (PMTCT) programmes within ANC services affects uptake. We explored barriers to uptake of integrated ANC services in a poor Zimbabwean community. Methods A cross-sectional survey was conducted among post-natal women at Mbare Clinic, Harare, between September 2010 and February 2011. Collected data included participant characteristics and ANC uptake. Logistic regression was conducted to determine factors associated with ANC registration. In-depth interviews were held with the first 21 survey participants who either did not register or registered after twenty-four weeks gestation to explore barriers. Interviews were analysed thematically. Results Two hundred and ninety-nine participants (mean age 26.1 years) were surveyed. They came from ultra-poor households, with mean household income of US$181. Only 229 (76.6%) had registered for ANC, at a mean gestation of 29.5 weeks. In multivariable analysis, household income was positively associated with ANC registration, odds ratio (OR) for a $10-increase in household income 1.02 (95% confidence interval, CI, 1.0–1.04), as was education which interacted with having planned the pregnancy (OR for planned pregnancy with completed ordinary level education 3.27 (95%CI 1.55–6.70). Divorced women were less likely to register than married women, OR 0.20 (95%CI 0.07–0.58). In the qualitative study, barriers to either ANC or PMTCT services limited uptake of integrated services. Women understood the importance of integrated services for PMTCT purposes and theirs and the babies’ health and appeared unable to admit to barriers which they deemed “stupid/irresponsible”, namely fear of HIV testing and disrespectful treatment by nurses. They represented these commonly recurring barriers as challenges that “other women” faced. The major proffered personal barrier was unaffordability of user fees, which was sometimes compounded by unsupportive husbands who were the breadwinners. Conclusion Women who delayed/did not register were aware of the importance of ANC and PMTCT but were either unable to afford or afraid to register. Addressing the identified challenges will not only be important for integrated PMTCT/ANC services but will also provide a model for dealing with challenges as countries scale up ‘treat all’ approaches.

Background: Major challenges are being experienced in medical education in sub-Saharan African Universities. These include emigration of faculty, infrequent curriculum review, inadequate training in medical education, poor investments in infrastructure and lack of faculty development programs. The USA government committed funding to improve the quality of medical education and research capacity in sub-Saharan Africa through the Medical Education Partnership Initiative (MEPI). Objectives: This article describes the implementation of faculty development at the University of Zimbabwe College of Health Sciences (UZCHS), a recipient of a MEPI award. Methods: Data sources included annual surveys and reports of UZCHS MEPI activities, exit evaluation reports of faculty development workshops; results of a survey conducted in 2015 at the end of the MEPI grant. Questionnaires were developed based on the MEPI Zimbabwe evaluation plan and logic model. Surveys were administered to faculty members, postgraduate and undergraduate students. Qualitative data was collected through in-depth key informer interviews of stakeholder. Findings: Different faculty development activities were implemented such as workshops, exchange visits, visiting professors program, advanced leadership training and curriculum development. The implementation of the activities brought positive developments to the college as confirmed by faculty and students. The majority of faculty interviewed (96%) confirmed that faculty development programs were very helpful in enhancing their expertise and skills. A similar number, i.e. 96%, also reported satisfaction with the training. Conclusions: We have described how the implementation of faculty development programs at the UZCHS contributed to the improvement of medical education at the College. The short term and long-term benefits of faculty development have been analyzed. Various forms of faculty development programs were described. Limitations of this analysis were the inability to collect data on students’ performance and the demonstration of changes in teaching performance.