A NEW COLLEGE OF PHYSICIANS East, Central and Southern Africa College of Physicians (ECSACOP)

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Editorial: HIV infection and the way forward for South Sudan

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"Well, not me, but other women do not register because..."- Barriers to seeking antenatal care in the context of prevention of mother-to-child transmission of HIV among Zimbabwean women: a mixed-methods study.

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$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

Manuscript title: Facilitators and barriers to cotrimoxazole prophylaxis among HIV exposed babies: a qualitative study from Harare, Zimbabwe.

BACKGROUND: Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally. Of note, Zimbabwe also provided nevirapine prophylaxis for HIV exposed babies, so the majority were giving nevirapine and CTX-p to their babies. METHODS: Between Feb-Dec 2011, the first 20 HIV infected mothers identified were invited for in-depth interview 4-5months postnatally. Interviews were recorded, transcribed, translated and analysed thematically. RESULTS: All women desired their baby's health above all else, and were determined to do all they could to ensure their wellbeing. They did not report problems remembering to give drugs. The baby's apparent good health was a huge motivator for continued adherence. However, most women reported that their husbands were less engaged in HIV care, refusing to be HIV tested and in some cases stealing drugs prescribed for their wives for themselves. In two instances the man stopped the woman from giving CTX-p to the baby either because of fear of side effects or not appreciating its importance. Stigma continues to be an important issue. Mothers reported being reluctant to disclose their HIV status to other people so found it difficult to collect prescription refills from the HIV clinic for fear of being seen by friends/relatives. Some women reported that it was hard to administer the drugs if there were people around at home. Other challenges faced were stock-outs of CTX-p at the clinic, which occurred three times in 2011. The baby would then go without CTX-p if the woman could not afford buying at a private pharmacy. CONCLUSIONS: The study highlights that adherence knowledge and desire alone is insufficient to overcome the familial and structural barriers to maintaining CTX-p. Improving adherence to CTX-p among HEI will require interventions to improve male involvement, reduce HIV stigma in communities and ensure adequate supply of drugs

Physical Properties of Emission-Line Galaxies at z ~ 2 from Near-Infrared Spectroscopy with Magellan FIRE

We present results from near-infrared spectroscopy of 26 emission-line galaxies at z ~ 2 obtained with the FIRE spectrometer on the Magellan Baade telescope. The sample was selected from the WISP survey, which uses the near-infrared grism of the Hubble Space Telescope Wide Field Camera 3 to detect emission-line galaxies over 0.3 < z < 2.3. Our FIRE follow-up spectroscopy (R~5000) over 1.0-2.5 micron permits detailed measurements of physical properties of the z~2 emission-line galaxies. Dust-corrected star formation rates for the sample range from ~5-100 M_sun yr-1. We derive a median metallicity for the sample of ~0.45 Z_sun, and the estimated stellar masses range from ~10^8.5 - 10^9.5 M_sun. The average ionization parameters measured for the sample are typically much higher than what is found for local star-forming galaxies. We derive composite spectra from the FIRE sample, from which we infer typical nebular electron densities of ~100-400 cm^-3. Based on the location of the galaxies and composite spectra on BPT diagrams, we do not find evidence for significant AGN activity in the sample. Most of the galaxies as well as the composites are offset in the BPT diagram toward higher [O III]/H-beta at a given [N II]/H-alpha, in agreement with other observations of z > 1 star-forming galaxies, but composite spectra derived from the sample do not show an appreciable offset from the local star-forming sequence on the [O III]/H-beta versus [S II]/H-alpha diagram. We infer a high nitrogen-to-oxygen abundance ratio from the composite spectrum, which may contribute to the offset of the high-redshift galaxies from the local star-forming sequence in the [O III]/H-beta versus [N II]/H-alpha diagram. We speculate that the elevated nitrogen abundance could result from substantial numbers of Wolf-Rayet stars in starbursting galaxies at z~2. (Abridged)Comment: Accepted for publication in Ap

The impact of different CD4 monitoring and switching strategies on mortality in HIV-infected African adults on antiretroviral therapy; an application of dynamic marginal structural models

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks

Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe.

BACKGROUND: Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated. METHODS: Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. RESULTS: 3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm(3)) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95$7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below$3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. CONCLUSIONS: There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test

Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial

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

Role of Faculty Development Programs in Medical Education at the University of Zimbabwe College of Health Sciences, Zimbabwe

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

Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

Background: Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods: Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results: 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions: Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients