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Background: Monitoring adherence presents a challenge in adolescents and it is prudent to explore several options for determining their level of adherence. This study sought to determine ART adherence levels in adolescents and young adults (on a tenofovir-containing regimen) failing ART as measured by self-reports, pill counts and DBS tenofovir concentrations and to compare levels of agreement among the methods and determine the ability of each method to predict virological suppression., Methods: This was a cohort study involving 107 adolescents and young adults between 10 and 24 years failing ART with viral load > 400copies/ml at enrolment. Pill count (PC) records, self-reports (SR) and DBS tenofovir concentrations (done by liquid Chromatography with tandem mass spectrometry (LC-MS/MS)) were used to determine adherence in adolescent participants failing ART in Harare. The latter was used as the reference method with a cut-off of 64 ng/ml. Determination of DBS tenofovir concentrations was also performed to rule out inadequate viral response due to low cumulative drug exposure despite high adherence (≥90 %). Longitudinal analysis was performed to determine the correlation of viral loads (VL) with adherence. The Kappa (k) coefficient was used to evaluate the level of agreement among the 3 methods., Results: Poor level of agreement was found between PC records and DBS tenofovir concentrations (k = -0.115). Moderate agreement was found between DBS and SR methods (k = 0.0557). Slight agreement was found between PC and SR methods (k = 0.0078). Adherence was dependent on age at HIV diagnosis (p = 0.0184) and ART initiation (p = 0.0265). Participants who were adherent were six times more likely to be suppressed at end point than their non-adherent counterparts (OR=5.7 CI 2.1 - 16.5, p < 0.0001)., Conclusions: Self-reported measure of adherence and pill counts exhibited poor agreement with the reference method used i.e. DBS tenofovir concentrations and are thus not effective methods of predicting virological suppression., Trial Identification: Participants in the present study were a subset of those in the PESU intervention ClinicalTrials.gov Identifier: NCT02833441., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up in Africa. However, clinical experience with DTG and patterns of HIV drug resistance (HIVDR) are sparse in Zimbabwe. We assessed virological, weight, and HIVDR outcomes among individuals initiating on a DTG-based ART., Design: We conducted a prospective cohort study among HIV-infected adult (≥18 years old) individuals attending care at Parirenyatwa hospital, Harare, Zimbabwe between October 2021 and April 2023., Methods: Viral load and weight were assessed at both baseline and follow-up (≥24weeks) visits. HIVDR genotyping was performed by Sanger sequencing among participants with virological failure (viral load ≥1000 copies/ml) at follow-up visit. Factors associated with weight gain were determined using logistic regression analysis on STATA 17.0., Results: One hundred and seventy-two participants were enrolled in the study. The median [interquartile range (IQR) age was 39 (29-48)] years whilst the median (IQR) CD4 + cell count and log 10 viral load at enrolment was 175 (58-328) cells/μl and 5.41 (4.80-5.74), respectively. After a median (IQR) duration of 27 (25-30) weeks on DTG, of the 131 participants with follow-up viral load data available, 129 (98%) had viral load less than 1000 copies/ml and among the 2 (2%) participants with viral load at least 1000 copies/ml, no emergent HIVDR was detected. We observed a significant increase in weight among the participants. The average weight gain was 5.25 kgs ( P  < 0.0001). Baseline CD4 + cell count at least 200 cells/μl was significantly associated with at a smaller weight gain [odds ratio (OR) = 0.26; 95% confidence interval (CI) 0.12-0.58, P  = 0.001]., Conclusion: We found high virological suppression and an increased weight among people initiating on DTG in a resource-limited setting. Encouragingly, HIVDR to DTG remains rare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The burden of non-communicable diseases (NCDs) in southern Africa is expanding and is superimposed on high HIV prevalence. Healthcare workers are a scarce resource; yet are vital to health systems. There are very limited studies on the burden of chronic conditions among healthcare workers in Africa, and none exploring multimorbidity (≥2 chronic conditions). We describe the epidemiology of infectious (HIV) and non-communicable chronic conditions, and multimorbidity, among Zimbabwean healthcare workers. Healthcare workers (≥18 years) in eight Zimbabwean provinces were invited to a voluntary, cross-sectional health-check, including HIV, diabetes, hypertension and mental health screening. Statistical analyses described the prevalence and risk factors for multimorbidity (two or more of HIV, diabetes, hypertension or common mental disorder) and each condition. Missing data were handled using multiple imputation. Among 6598 healthcare workers (July 2020-July 2022) participating in the health-check, median age was 37 years (interquartile range 29-44), 79% were women and 10% knew they were living with HIV. Half had at least one chronic condition: 11% were living with HIV, 36% had elevated blood pressure, 12% had elevated HbA1c and 11% had symptoms of common mental disorder. The overall prevalence of multimorbidity was 15% (95% CI: 13-17%); 39% (95% CI: 36-43%) among people aged 50 and older. Whilst most HIV was diagnosed and treated, other chronic conditions were usually undiagnosed or uncontrolled. Limiting our definition of multimorbidity to two or more screened conditions sought to reduce bias due to access to diagnosis, however, may have led to a lower reported prevalence than that found using a wider definition. Half of healthcare workers screened were living with a chronic condition; one in seven had multimorbidity. Other than HIV, most conditions were undiagnosed or untreated. Multisectoral action to implement contextually relevant, chronic disease services in Africa is urgently needed. Specific attention on health workers is required to protect and retain this critical workforce., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Calderwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health workers are essential for a functioning healthcare system, and their own health is often not addressed. During the COVID-19 pandemic health workers were at high risk of SARS-CoV-2 infection whilst coping with increased healthcare demand. Here we report the development, implementation, and uptake of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases for health workers in Zimbabwe during the COVID-19 pandemic. Health checks were offered to health workers in public and private health facilities from July 2020 to June 2022. Data on the number of health workers accessing the service and yield of screening was collected. Workshops and in-depth interviews were conducted to explore the perceptions and experiences of clients and service providers. 6598 health workers across 48 health facilities accessed the service. Among those reached, 5215 (79%) were women, the median age was 37 (IQR: 29-44) years and the largest proportion were nurses (n = 2092, 32%). 149 (2.3%) healthcare workers tested positive for SARS-CoV-2. Uptake of screening services was almost 100% for all screened conditions except HIV. The most common conditions detected through screening were elevated blood pressure (n = 1249; 19%), elevated HbA1c (n = 428; 7.7%) and common mental disorder (n = 645; 9.8%). Process evaluation showed high acceptability of the service. Key enablers for health workers accessing the service included free and comprehensive service provision, and availability of reliable point-of-care screening methods. Implementation of a comprehensive health check for health workers was feasible, acceptable, and effective, even during a pandemic. Conventional occupational health programmes focus on infectious diseases. In a society where even health workers cannot afford health care, free comprehensive occupational health services may address unmet needs in prevention, diagnosis, and treatment for chronic non-communicable conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marambire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centres for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 3,086 healthcare workers employed at 43 facilities who participated in the study, 2,986 (97%, 95% CI [92%-100%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Taruvinga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: HIV/AIDS mortality remains significantly high in sub-Saharan Africa, mostly driven by opportunistic infections and advanced HIV disease (AHD). This study aimed to assess CD4 + cell count recovery following ART initiation and factors associated with immune reconstitution., Methods: We conducted a prospective cohort study between 2015 and 2016. HIV-infected adults (≥18 years) with AHD (CD4 + cell count ≤100 cells/μl) receiving care at 20 outpatient HIV treatment facilities in Harare, Zimbabwe were enrolled. CD4 + cell count recovery (CD4 + cell count >200 cells/μl) was assessed following 12-month ART initiation and factors associated with immune reconstitution were investigated using logistic regression analysis. All statistical analyses were performed on Statistical Package for the Social Sciences (SPSS) version 23., Results: 1320 participants were enrolled and 56.4% were males. The median (interquartile range, IQR) age was 37 (32-43) years. Tuberculosis was seen in 16.0%. Of the 739 participants that had CD4 + cell count at 12 months, CD4 + cell count recovery above 200 cells/μl was observed in 163 (22.1%) participants. Median (IQR) CD4 + cell count at 12-months increased to 127 (75-190) cells/μl from 31 (14-55) at baseline. Factors associated with CD4 + cell count recovery were younger age at baseline [odds ratio (OR) ≥40/<40  = 0.58, 95% confidence interval (CI): 0.40-0.85, P  = 0.005), sex (OR female/male  = 2.07, 95% CI: 1.44-2.99, P  < 0.0001) and baseline CD4 + cell count (OR ≥50/<50  = 1.60, 95% CI: 1.10-2.33, P  = 0.013)., Conclusion: A significant proportion (77.9%) of patients seeking care with AHD in a resource limited setting failed to recover a CD4 + cell count >200 cells/μl. Male sex, older age and low CD4 + cell count at ART initiation were factors associated with poor immune reconstitution. Better differentiated care deliveries targeting this vulnerable population are critical for improving clinical outcomes and quality of life of the patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: We would like to thank all investigators and participants in the AMBITION trial and associated substudies, community members, and the funders of the trial. The AMBITION trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (TRIA2015-1092), and the Wellcome Trust/Medical Research Council (MRC) UK/UKAID Joint Global Health Trials (MR/P006922/1). Additional funding was provided by the National Institute for Health Research (NIHR) through a Global Health Research Professorship (RP-2017-08-ST2-012, to JNJ) with aid from the UK Government to support global health research. JNJ is funded by the National Institute for Health and Care Research (NIHR) through a Global Health Research Professorship (RP-2017-08-ST2-012) using UK aid from the UK Government to support global health research and received grant payments from the NIHR and EDCTP to his institution. RC received consulting fees to serve as methodologist for the updated WHO guideline on cryptococcal meningitis. TSH and DSL received support for the underlying AMBITION trial to institution from EDCTP, MRC, and Wellcome Trust, UK aid from the UK Government to support global health research, and provision of drug for the underlying AMBITION trial from Gilead. All other authors declare no competing interests. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The writing of this Comment was supported by a grant from the Bill & Melinda Gates Foundation. We are grateful to Susan L Norris and Rebekah Thomas for providing comments on an earlier draft.

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log 10 VL were 39 (29-48) years and 5.41 (4.80-5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25-30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.

Presentation to care with advanced HIV disease (AHD) is a significant problem in sub-Saharan Africa. We evaluated factors associated with immune recovery among individuals presenting to care with AHD in Zimbabwe. We conducted a retrospective evaluation of outcomes among adult (>18 years old) individuals with AHD (CD4 count ≤200 cells/mm 3 ) receiving care at 18 outpatient primary care clinics in Harare, Zimbabwe. Baseline and 12-month CD4 count data were extracted from medical records. CD4 count recovery (defined as CD4 count >200 cells/mm 3 ) after 12 months on non-nucleotide reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) regimen was determined and factors associated with CD4 count recovery were established using logistic regression. All statistical analysis was performed on SPSS v23. A total of 1,338 participant records were included in the analysis. The median interquartile range (IQR) age was 37 (30-43) years and 52% were females. The baseline median (IQR) CD4 count was 50 (28-75) cells/mm 3 and was significantly lower among patients with history of cryptococcal meningitis compared to those without [25 (10-52) vs. 52 (32-77), respectively; p  = .0009]. The median (IQR) CD4 count at 12 months after ART initiation increased from 50 (28-75) at baseline to 180 (92-290) cells/mm 3 . Immune recovery with a CD4 count >200 cells/mm 3 was observed in 181/417 (43%). Male gender and low baseline CD4 count were strong predictors of poor immunological recovery on ART. Immunological recovery following ART initiation was 43% among individuals with AHD. Male patients are most vulnerable to persistent immunological failure. Clinical Trial Registration number: NCT02434172.

Background: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis., Methods: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed., Findings: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda., Interpretation: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays., Funding: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research., Translations: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TSH was the recipient of an investigator award to his institution from Gilead Sciences; speaker fees from Pfizer and Gilead Sciences; and serves as an adviser for F2G. JNJ and GM both declare speaker fees from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cryptococcal disease (CD) is a leading cause of mortality among individuals with advanced HIV disease (AHD). Screening with serum cryptococcal antigen (sCrAg) lateral flow assay (LFA) enables early detection of subclinical disease but requires venipuncture and laboratory processing. Clinic-based point of care (POC) CrAg screening tests using urine or fingerprick whole blood could facilitate early diagnosis of CD. We evaluated the diagnostic performance of POC clinic-based fingerprick whole blood and urine CrAg compared to the gold standard laboratory sCrAg LFA in screening for CD among asymptomatic individuals with CD4 counts of <200 cells/μL in Harare, Zimbabwe. sCrAg positive participants who consented to a lumbar puncture also had cerebrospinal fluid (CSF) CrAg testing and titers for CSF-positive specimens. A total of 1,333 individuals were screened, and over half (56.6%) were males. The median (interquartile range) CD4 count was 27.5 (11-46) cells/μL. We found a sensitivity of 63.8% (95% CI: 54.8-72.1) and specificity of 84.0% (95% CI: 81.7-86.0) for urine CrAg, and a sensitivity of 48.0% (95% CI: 39.1-57.1) and specificity of 99.5% (95% CI: 98.9-99.8) was found for fingerprick whole blood. The sensitivity of both POC CrAg tests increased in individuals with sCrAg titers of ≥1:160, CD4 count of <50 cells/μL and disseminated central nervous system (CNS) disease. Clinic-based POC urine and fingerprick whole blood CrAg testing performed better in screening for CD among AHD patients with CNS disease. More sensitive assays to identify AHD patients with asymptomatic CD are needed. IMPORTANCE Cryptococcal disease (CD) remains a leading cause of morbidity and mortality among individuals with advanced HIV disease (AHD). Identifying point of care (POC) approaches to screening for CD in asymptomatic individuals is important to guide therapeutic management. We evaluated the use of POC fingerprick whole blood and urine testing for cryptococcal disease in patients with AHD as compared with laboratory-based serum antigen testing. POC fingerprick whole blood and urine testing had low sensitivity and specificity in asymptomatic individuals with AHD. Most analysis has focused on evaluating test performance in symptomatic individuals. Here we show that POC testing with whole blood and urine samples should not be used to screen for asymptomatic CD in AHD.

Background: Healthcare workers (HCWs) have experienced anxiety and psychological distress during the COVID-19 pandemic. We established and report findings from an occupational health programme for HCWs in Zimbabwe that offered screening for SARS-CoV-2 with integrated screening for comorbidities including common mental disorder (CMD) and referral for counselling., Methods: Quantitative outcomes were fearfulness about COVID-19, the Shona Symptom Questionnaire (SSQ-14) score (cutpoint 8/14) and the number and proportion of HCWs offered referral for counselling, accepting referral and counselled. We used chi square tests to identify factors associated with fearfulness, and logistic regression was used to model the association of fearfulness with wave, adjusting for variables identified using a DAG. Qualitative data included 18 in-depth interviews, two workshops conducted with HCWs and written feedback from counsellors, analysed concurrently with data collection using thematic analysis., Results: Between 27 July 2020-31 July 2021, spanning three SARS-CoV-2 waves, the occupational health programme was accessed by 3577 HCWs from 22 facilities. The median age was 37 (IQR 30-43) years, 81.9% were women, 41.7% said they felt fearful about COVID-19 and 12.1% had an SSQ-14 score ≥ 8. A total of 501 HCWs were offered referral for counselling, 78.4% accepted and 68.9% had ≥1 counselling session. Adjusting for setting and role, wave 2 was associated with increased fearfulness over wave 1 (OR = 1.26, 95% CI 1.00-1.60). Qualitative data showed high levels of anxiety, psychosomatic symptoms and burnout related to the pandemic. Mental wellbeing was affected by financial insecurity, unmet physical health needs and inability to provide quality care within a fragile health system., Conclusions: HCWs in Zimbabwe experience a high burden of mental health symptoms, intensified by the COVID-19 pandemic. Sustainable mental health interventions must be multisectoral addressing mental, physical and financial wellbeing., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known., Methods: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin., Results: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log 10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log 10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%)., Conclusions: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: By the end of July 2021 Zimbabwe, has reported over 100,000 SARS-CoV-2 infections. The true number of SARS-CoV-2 infections is likely to be much higher. We conducted a seroprevalence survey to estimate the prevalence of past SARS-CoV-2 in three high-density communities in Harare, Zimbabwe before and after the second wave of SARS-CoV-2., Methods: Between November 2020 and April 2021 we conducted a cross-sectional study of randomly selected households in three high-density communities (Budiriro, Highfield and Mbare) in Harare. Consenting participants answered a questionnaire and a dried blood spot sample was taken. Samples were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche e801 platform., Findings: A total of 2340 individuals participated in the study. SARS-CoV-2 antibody results were available for 70·1% (620/885) and 73·1% (1530/2093) of eligible participants in 2020 and 2021. The median age was 22 (IQR 10-37) years and 978 (45·5%) were men. SARS-CoV-2 seroprevalence was 19·0% (95% CI 15·1-23·5%) in 2020 and 53·0% (95% CI 49·6-56·4) in 2021. The prevalence ratio was 2·47 (95% CI 1·94-3·15) comparing 2020 with 2021 after adjusting for age, sex, and community. Almost half of all participants who tested positive reported no symptoms in the preceding six months., Interpretation: Following the second wave, one in two people had been infected with SARS-CoV-2 suggesting high levels of community transmission. Our results suggest that 184,800 (172,900-196,700) SARS-CoV-2 infections occurred in these three communities alone, greatly exceeding the reported number of cases for the whole city. Further seroprevalence surveys are needed to understand transmission during the current third wave despite high prevalence of past infections., Funding: GCRF, Government of Canada, Wellcome Trust, Bavarian State Ministry of Sciences, Research, and the Arts., Competing Interests: AW declared that Roche provided reagents and machine for discounted rates for all projects involving SARS-CoV-2 serology. AW holds part of a patent application with the German Patent and Trade Mark Office relating to safe transport of DBS for analytical purpose; this application was not used in the current study. RAF received funding from the Wellcome Trust since 2017, is a member of the Zimbabwe national COVID19 Advisory Panel and a member of the CDC Africa Strategic Advisory Group of Experts for COVID19. All the other authors report no conflicts., (© 2021 The Author(s).)

Pretreatment drug resistance (PDR) can compromise antiretroviral therapy (ART) efficacy and undermine the WHO targets to end the AIDS epidemic as a public health threat by 2030. Thus, we examined the level of PDR in Harare, Zimbabwe. Eligible study participants were adults who were ART naive or individuals with previous ART exposure reinitiating treatment, recruited between October 2018 and February 2020 in a HIV ART treatment clinic, in Harare. HIV drug resistance tests were performed for all specimens with viral load ≥400 copies/mL and interpreted using the Stanford HIVDB Algorithm. Chi-square test or Fisher's exact test was used for comparison of proportions of PDR across ART-naive or prior ART-exposed participants. All statistical analyses were performed using Stata version 14. Overall, 120 samples were genotyped of whom 104 were ART naive and 16 reported previous ART exposure. The overall PDR frequency among all participants was 31% [95% confidence interval (CI): 22.5-39.6]. PDR to any non-nucleotide reverse transcriptase inhibitor (NNRTI) was reported in 29% (95% CI: 21.0-37.9). PDR to nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors were low, found in 3% (95% CI: 0.9-8.2) and 1% (95% CI: 0.02-4.52), respectively. PDR to NNRTIs [efavirenz/nevirapine (EFV/NVP)] was found in 17% (95% CI: 10.5-24.6) and was more than six times higher among people with previous ART exposure than ART-naive people: 63% versus 10%, p  < .001. Our study shows that PDR to NNRTIs in Zimbabwe has remarkably increased from the 10.9% prevalence reported in the 2016 WHO survey. Addressing PDR at a national level is a critical need and will be facilitated by fast-tracking the transition to dolutegravir in first-line ART regimens.

Objectives: Our study's primary objective was to compare 1-year survival rates between serum cryptococcal antigen (sCrAg)-positive and sCrAg-negative HIV-positive individuals with CD4+ cell counts less than 100 cells/μl without symptoms of meningitis in Zimbabwe., Design: This was a prospective cohort study., Methods: Participants were enrolled as either sCrAg-positive or sCrAg-negative and followed up for 52 weeks or less, with death as the outcome. Lumbar punctures were recommended to all sCrAg-positives and inpatient management with intravenous amphotericin B and high-dose fluconazole was recommended to those with disseminated Cryptococcus. Antiretroviral therapy was initiated immediately in sCrAg-negatives and after at least 4 weeks following initiation of antifungals in sCrAg-positives. Multivariable logistic regression models were used to determine risk factors for mortality., Results: We enrolled 1320 participants and 130 (9.8%) were sCrAg positive, with a median sCrAg titre of 1 : 20. Sixty-six (50.8%) sCrAg-positives had lumbar punctures and 16.7% (11/66) had central nervous system (CNS) dissemination. Cryptococcal blood cultures were performed in 129 sCrAg-positives, with 10 (7.8%) being positive. One-year (48-52 weeks) survival rates were 83.9 and 76.1% in sCrAg-negatives and sCrAg-positives, respectively, P = 0.011. Factors associated with increased mortality were a positive sCrAg, CD4+ cell count less than 50 cells/μl and having presumptive tuberculosis (TB) symptoms., Conclusion: Our study reports a high prevalence of subclinical cryptococcal antigenemia and reiterates the importance of TB and a positive sCrAg as risk factors for mortality in advanced HIV disease (AHD). Therefore, TB and sCrAg screening remains a crucial component of AHD package, hence it should always be part of the comprehensive clinical evaluation in AHD patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: pre-treatment drug resistance (PDR) can compromise the 3 rd 95-95-95 global target for viral load suppression. The high complexity and cost of genotyping assays limits routine testing in many resource limited settings (RLS). We assessed the performance of a rapid HIV-1 drug resistance assay, the Pan Degenerate Amplification and Adaptation (PANDAA) assay when screening for significant HIV-1 drug resistance mutations (DRMs) such as K65R, K103NS, M184VI, Y181C and G190A. Methods: we used previously generated amplicons from a cross-sectional study conducted between October 2018 and February 2020 of HIV-1 infected antiretroviral therapy (ART)-naïve or those reinitiating 1 st line ART (18 years or older). The performance of the PANDAA assay in screening K65R, K103NS, M184VI, Y181C, and G190A mutations compared to the reference assay, Sanger sequencing was evaluated by Cohen´s kappa coefficient on Stata version 14 (StataCorp LP, College Station, TX, USA)., Results: one hundred and twenty samples previously characterized by Sanger sequencing were assessed using PANDAA. PDR was found in 14% (17/120). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was higher at 13% (16/120) than PDR to nucleotide reverse transcriptase inhibitors (NRTIs), 3% (3/120). The PANDAA assay showed a strong agreement with the reference assay, i.e. Sanger sequencing for all five target DRMs (kappa (95%CI); 0.93 (0.78-0.98)) and NNRTI DRMs (kappa (95%CI); 0.93 (0.77-0.980), and a perfect agreement for NRTI DRMs (kappa (95%CI); 1.00 (0.54-1.00))., Conclusion: the PANDAA assay is a simple and rapid method to identify significant HIV DRMs in plasma samples as an alternative to Sanger sequencing in many RLS., Competing Interests: The authors declare no competing interests., (Copyright: Vinie Kouamou et al.)

Background: Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF)., Methods: We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing., Results: The participants' median (interquartile range (IQR)) age was 18.1 (IQR: 15.1-20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146)., Conclusion: A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART., Trial Registration: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441.

Background: In order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient facing health workers. Our first aim was to determine both the infection status and seroprevalence of SARS-CoV-2 in health workers. Our second aim was to evaluate the occupational and demographic predictors of seropositivity to inform the country's infection prevention and control (IPC) strategy., Methods and Principal Findings: We invited 713 staff members at 24 out of 35 health facilities in the City of Bulawayo in Zimbabwe. Compliance to testing was defined as the willingness to uptake COVID-19 testing by answering a questionnaire and providing samples for both antibody testing and PCR testing. SARS-COV-2 antibodies were detected using a rapid diagnostic test kit and SAR-COV-2 infection was determined by real-time (RT)-PCR. Of the 713 participants, 635(89%) consented to answering the questionnaire and providing blood sample for antibody testing while 560 (78.5%) agreed to provide nasopharyngeal swabs for the PCR SARS-CoV-2 testing. Of the 635 people (aged 18-73) providing a blood sample 39.1% reported a history of past COVID-19 symptoms while 14.2% reported having current symptoms of COVID-19. The most-prevalent co-morbidity among this group was hypertension (22.0%) followed by asthma (7.0%) and diabetes (6.0%). The SARS-CoV-2 sero-prevalence was 8.9%. Of the 560 participants tested for SARS-CoV-2 infection, 2 participants (0.36%) were positive for SAR-CoV-2 infection by PCR testing. None of the SARS-CoV-2 antibody positive people were positive for SAR-CoV-2 infection by PCR testing., Conclusion and Interpretation: In addition to clinical staff, several patient-facing health workers were characterised within Zimbabwe's health system and the seroprevalence data indicated that previous exposure to SAR-CoV-2 had occurred across the full spectrum of patient-facing staff with nurses and nurse aides having the highest seroprevalence. Our results highlight the need for including the various health workers in IPC strategies in health centres to ensure effective biosecurity and biosafety., Competing Interests: The authors have declared that no competing interests exist.

HIV drug resistance (HIVDR) is a barrier to sustained virologic suppression in low- and middle-income countries (LMICs). Point mutation assays targeting priority drug resistance mutations (DRMs) are being evaluated to improve access to HIVDR testing. In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS). Plasma samples from adolescents and young adults (aged 10 to 24 years) failing antiretroviral therapy (viral load, >1,000 copies/ml on 2 consecutive occasions 1 month apart) were analyzed. Sensitivity and specificity of the PANDAA assay were determined by a proprietary application designed by Aldatu Biosciences. Agreement between genotyping methods was evaluated using Cohen's kappa coefficient. One hundred fifty samples previously characterized by Sanger sequencing were evaluated using PANDAA. For all DRMs detected, PANDAA showed a sensitivity and specificity of 98% and 94%, respectively. For nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 98% (95% confidence interval [CI], 92% to 100%) and 100% (94% to 100%), respectively. For non-nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 100% (97% to 100%) and 76% (61% to 87%), respectively. PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720). Of the 21 false-positive samples genotyped by PANDAA, only 6 (29%) were identified as low-abundance variants by NGS. With the high sensitivity and specificity to detect major DRMs, PANDAA could represent a simple and rapid alternative HIVDR assay in LMICs., (Copyright © 2020 American Society for Microbiology.)

Objectives: The integrase strand inhibitor dolutegravir (DTG) combined with tenofovir and lamivudine (TLD) is a single tablet regimen recommended for 1st, 2nd and 3rd-line public health antiretroviral therapy (ART). We determined drug resistance mutations (DRMs) and evaluated the predictive efficacy of a TLD containing regimen for viremic adolescents and young adults in Harare, Zimbabwe., Methods: We sequenced plasma viral RNA from HIV-1-infected adolescents and young adults on 1st and 2nd-line ART with confirmed virologic failure (viral load >1000 copies/ml) and calculated total genotypic susceptibility scores to current 2nd, 3rd line and DTG regimens., Results: A total of 160 participants were genotyped; 112 (70%) on 1st line and 48 (30%) on 2nd line, median (interquartile range) age 18 (15-19) and duration of ART (interquartile range) was 6 (4-8) years. Major DRMs were present in 94 and 67% of 1st and 2nd-line failures, respectively (P < 0.001). Dual class resistance to nucleotide reverse transcriptase inhibitors and nonnucleotide reverse transcriptase inhibitors was detected in 96 (60%) of 1st-line failures; protease inhibitor DRMs were detected in a minority (10%) of 2nd-line failures. A total genotypic susceptibility score of 2 or less may risk protease inhibitor or DTG monotherapy in 11 and 42% of 1st-line failures switching to 2nd-line protease inhibitor and TLD respectively., Conclusion: Among adolescents and young adults, current protease inhibitor-based 2nd-line therapies are poorly tolerated, more expensive and adherence is poor. In 1st-line failure, implementation of TLD for many adolescents and young adults on long-term ART may require additional active drug(s). Drug resistance surveillance and susceptibility scores may inform strategies for the implementation of TLD.

Background: Data on chronic kidney disease development in HIV infection is important towards building a comprehensive knowledge of HIV, ageing and polypharmacy in Africa. Several previous studies on tenofovir-associated kidney disease in Africa have shown conflicting results. This review summarises what is known about the development of kidney disease in HIV-positive African patients on tenofovir disoproxil fumarate (TDF)-containing ART. We set out to document the occurrence of kidney disease in HIV-positive Africans on TDF-containing ART in population-based studies and to evaluate the renal safety of TDF in Africans., Methods: We conducted a systemic review using published studies which were identified through a computerized search of original research using the Medline/PubMed database, EMBASE, EBM Reviews, Proquest Google Scholar and Global Health reported from inception until 5 October 2017. Two reviewers independently abstracted the data and performed quality assessment of the included studies. We screened 595 articles and included 31 in the qualitative analysis performed., Results: A total of 106 406 patients (of whom 66,681 were on Tenofovir) were involved in these 31 studies with sample sizes ranging from 30 to 62,230. Duration on tenofovir-containing ART ranged from those initiating ART at baseline to those who received TDF for up to 9 years. All but one of the studies involved only patients 16 years and older. The studies had differing definitions of kidney dysfunction and were of variable study design quality. The documented outcomes had substantial discrepancies across the studies, most likely due to methodological differences, study size and disparate outcome definitions., Conclusions: Our review identified studies in Africans reporting statistically significant renal function decline associated with TDF use but the clinical significance of this effect was not enough to contraindicate its continued use in ART regimens. Consistent with studies in other populations, patients are at greater risk if they have pre-existing renal disease and are more advanced in age. More research is needed on paediatric populations under 16 years of age. Trial registration This review was registered on Prospero (registration number CRD42018078717).

Introduction: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation., Methods and Analysis: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial., Ethics and Dissemination: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings., Trial Registration: ISRCTN 7250 9687; Pre-results., Competing Interests: Competing interests: JNJ and TSH were the recipients of a Gilead Investigator Initiated Award (completed). TSH has received speaker fees from Gilead Sciences and Pfizer., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.

Background: There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients., Methods: We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/µL; 125 CrAg- and CrAg+ but cerebrospinal fluid CrAg- by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay., Results: GXM-IgG, -IgM, and -IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg- patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG, -IgG2, and -IgM, this model had an 80.4% probability (95% confidence interval, 0.75-0.86) of predicting CrAg+ status., Conclusions: Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

Background: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen)., Methods: An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance., Discussion: A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment., Trial Registration: ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.

Background: Increasing numbers of children are requiring long-term HIV care and antiretroviral treatment (ART) in public ART programs in Africa, but temporal trends and long-term outcomes in care remain poorly understood., Methods: We analyzed outcomes in a longitudinal cohort of infants (<2 years of age) and children (2-10 years of age) enrolling in a public tertiary ART center in Zimbabwe over an 8-year period (2004-2012)., Results: The clinic enrolled 1644 infants and children; the median age at enrollment was 39 months (interquartile range: 14-79), with a median CD4% of 17.0 (interquartile range: 11-24) in infants and 15.0 (9%-23%) in children (P = 0.0007). Among those linked to care, 33.5% dropped out of care within the first 3 months of enrollment. After implementation of revised guidelines in 2009, decentralization of care and increased access to prevention of mother to child transmission services, we observed an increase in infants (48.9%-68.3%; P < 0.0001) and children (48.9%-68.3%; P < 0.0001) remaining in care for more than 3 months. Children enrolled from 2009 were younger, had lower World Health Organization clinical stage, improved baseline CD4 counts than those who enrolled in 2004-2008. Long-term retention in care also improved with decreasing risk of loss from care at 36 months for infants enrolled from 2009 (aHR: 0.57; 95% confidence interval: 0.34-0.95; P = 0.031). ART eligibility at enrollment was a significant predictor of long-term retention in care, while delayed ART initiation after 5 years of age resulted in failure to fully reconstitute CD4 counts to age-appropriate levels despite prolonged ART., Conclusions: Significant improvements have been made in engaging and retaining children in care in public ART programs in Zimbabwe. Guideline and policy changes that increase access and eligibility will likely to continue to support improvement in pediatric HIV outcomes.

Background: Sub-Saharan Africa has an inadequate number of health professionals, leading to a reduced capacity to respond to health challenges, including HIV/AIDS. From 2010 to 2015, the Medical Education Partnership Initiative (MEPI)-sponsored by the U.S. Presidents Emergency Plan for AIDS Relief (PEPFAR) and the National Institutes of Health (NIH)-was enthusiastically taken up by the University of Zimbabwe College of Health Sciences (UZCHS) and 12 other sub-Saharan African universities to develop models of training to improve medical education and research capacity. In this article, we describe the outcomes and challenges of MEPI in Zimbabwe., Methods: UZCHS in partnership with the University of Colorado, Denver; Stanford University; University of Cape Town; University College London; and King's College London designed the Novel Education Clinical Trainees and Researchers (NECTAR) program and 2 linked awards addressing cardiovascular disease and mental health to pursue MEPI objectives. A range of medical education and research capacity-focused programs were implemented, including faculty development, research support, mentored scholars, visiting professors, community-based education, information and technology support, cross-cutting curricula, and collaboration with partner universities and the ministries of health and education. We analyzed quantitative and qualitative data from several data sources, including annual surveys of faculty, students, and other stakeholders; workshop exit surveys; and key informant interviews with NECTAR administrators and leaders and the UZCHS dean., Findings: Improved Internet connectivity and electronic resource availability were early successes of NECTAR. Over the 5-year period, 69% (115 of 166) of faculty members attended at least 1 of 15 faculty development workshops. Forty-one faculty members underwent 1-year advanced faculty development training in medical education and leadership. Thirty-three mentored research scholars were trained under NECTAR, and 52 and 12 in cardiovascular and mental health programs, respectively. Twelve MEPI scholars had joined faculty by 2015. Full-time faculty grew by 36% (122 to 166), annual postgraduate and medical student enrollment increased by 61% (75 to 121) and 71% (123 to 210), respectively. To institutionalize and sustain MEPI innovations, the Research Support Center and the Department of Health Professions Education were established at UZCHS., Conclusion: MEPI has synergistically revitalized medical education, research capacity, and leadership at UZCHS. Investments in creating a new research center, health professions education department, and, programs have laid the foundation to help sustain faculty development and research capacity in the country., (© Hakim et al.)

Background: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations., Methods: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models., Findings: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I 2 =45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies., Interpretation: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA., Competing Interests: Conflict of interest The authors declare no conflict of interest.

Few evidence-based interventions to improve adherence to antiretroviral therapy have been adapted for use in Africa. We selected, culturally adapted and tested the feasibility of a cognitive-behavioural intervention for adherence and for delivery in a clinic setting in Harare, Zimbabwe. The feasibility of the intervention was evaluated using a mixed-methods assessment, including ratings of provider fidelity of intervention delivery, and qualitative assessments of feasibility using individual semi-structured interviews with counsellors (n=4) and patients (n=15). The intervention was feasible and acceptable when administered to 42 patients and resulted in improved self-reported adherence in a subset of 15 patients who were followed up after 6months.

Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93; P < 0.0001). The mean difference between DBS and plasma VL values was -1.06 log 10 copies/ml (95% confidence interval [CI], -1.17, -0.97; P < 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system., (Copyright © 2017 Makadzange et al.)

Introduction: Problem-based Learning (PBL) curricula, like all curricula, require systematic evaluation as there is a risk of implementing a dysfunctional PBL curriculum. The study intended to evaluate the PBL curriculum delivery from the perspective of the clerkship students at the University of Botswana-Faculty of Medicine., Methods: A cross-sectional study was conducted among clerkship students in Family Medicine, Paediatrics, Internal Medicine and Surgery. During a 4-week period, each respondent completed weekly a questionnaire based survey tool. The three part questionnaire consisted of demographic data, 'seven-jumps' adapted from a 'typical' PBL tool to evaluate PBL process and 11 items 'adopted 'from the Short-Questionnaire-to-Evaluate-the-Effectiveness-of-Tutors in the PBL tool to evaluate the PBL facilitation with open ended questions at the end., Results: Of the 81 eligible participants, 89% (n=72) responded. We collected back 141 (49%) forms out of the 288 expected (72 X 4 weeks). PBL first sessions took place all the time only in Family Medicine and in about 75% of the time in Pediatrics but none were conducted in the other disciplines. Overall, they evaluated the PBL process as 'good' (median= 8 /10) and the PBL facilitation as 'very good' (median=9 /10). Students appeared to have differing opinions on the preferred approach to the nature of patient problems that the PBL sessions should be structured around., Conclusion: Despite students rating PBL process as 'good' and facilitation as 'very good', PBL first sessions were not consistently undertaken.

Background: The Medical Education Partnership Initiative, has helped to mitigate the digital divide in Africa. The aim of the study was to assess the level of access, attitude, and training concerning meaningful use of electronic resources and EBM among medical students at an African medical school., Methods: The study involved medical students at the University of Zimbabwe College of Health Sciences, Harare. The needs assessment tool consisted of a 21-question, paper-based, voluntary and anonymous survey., Results: A total of 61/67 (91%), responded to the survey. 60% of the medical students were 'third-year medical students'. Among medical students, 85% of responders had access to digital medical resources, but 54% still preferred printed medical textbooks. Although 25% of responders had received training in EBM, but only 7% found it adequate. 98% of the participants did not receive formal training in journal club presentation or analytical reading of medical literature, but 77 % of them showed interest in learning these skills., Conclusion: Lack of training in EBM, journal club presentation and analytical reading skills have limited the impact of upgraded technology in enhancing the level of knowledge. This impact can be boosted by developing a curriculum with skills necessary in using EBM.

Introduction: Enumeration of CD4+ T lymphocytes is important for pre-ART disease staging and screening for opportunistic infections, however access to CD4 testing in resource limited settings is poor. Point of care (POC) technologies can facilitate improved access to CD4 testing. We evaluated the analytical performance of a novel POC device the FACSPresto compared to the FACSCalibur as a reference standard and to the PIMA, a POC device in widespread use in sub-Saharan Africa., Method: Specimens were obtained from 253 HIV infected adults. Venous blood samples were analyzed on the FACSPresto and the FACSCalibur, in a subset of 41 samples additional analysis was done on the PIMA., Results: The absolute CD4 count results obtained on the FACSPresto were comparable to those on the FACSCalibur with low absolute (9.5cells/μl) and relative bias (3.2%). Bias in CD4% values was also low (1.06%) with a relative bias of 4.9%. The sensitivity was lower at a CD4 count threshold of ≤350cells/μl compared with ≤500cells/μl (84.9% vs. 92.8%) resulting in a high upward misclassification rate at low CD4 counts. Specificity at thresholds of ≤350cells/μl and ≤500cells/μl were 96.6% and 96.8% respectively. The PIMA had a high absolute (-68.6cells/μl) and relative bias (-10.5%) when compared with the FACSCalibur. At thresholds of ≤350cells/μl and ≤500cells/μl the sensitivity was 100% and 95.5% respectively; specificity was 85.7% and 84.2% respectively. The coefficients of repeatability were 4.13%, 5.29% and 9.8% respectively., Discussion: The analytic performance of the FACSPresto against the reference standard was very good with better agreement and precision than the PIMA. The FACSPresto had comparable sensitivity at a threshold of 500 cells/μl and better specificity than the PIMA. However the FACSPresto showed reduced sensitivity at low CD4 count thresholds., Conclusion: The FACSPresto can be reliably used as a POC device for enumerating absolute CD4 count and CD4% values.

Objective: To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country., Methods: A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10-19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record., Results: Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10 y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates., Conclusions: During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.

Background: Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM., Methodology/design: This is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥ 18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400-800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat., Trial Registration: ISRCTN10248064. Date of Registration: 22 January 2014.

Background: Co-infections have become significant causes of morbidity and mortality in Human Immunodeficiency Virus (HIV) infected people. Due to shared routes of transmission, co-infection of HIV with Hepatitis B (HBV) and/or Hepatitis C (HCV) should be expected. In Zimbabwe, screening for both viruses in HIV infected people prior to treatment is not routinely practised despite the World Health Organisation (WHO) guidelines (2013) prioritising treatment where these co-infections exist., Objective: To determine the prevalence of HBV and HCV infection in HIV infected adults at a public sector HIV clinic in Zimbabwe and to determine risk factors associated with these infections., Design and Setting: An analytical cross-sectional survey carried out among systematically randomly sampled HIV infected patients coming for treatment between March and July 2012 at Parirenyatwa Hospital Opportunistic Infection Clinic., Materials and Methods: Blood samples were tested for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibodies (anti-HCV). Demographic data and exposure to risk factors were collected., Results: 228 antiretroviral therapy (ART) naive adults were enrolled. 7.9% (18/228) were HBsAg positive and 0.9% (2/228) were anti-HCV positive. None of the participants were infected with both viruses., Conclusions: The prevalence of HBV has not changed during this HIV era and there is no significant HCV infection in this public sector clinic which serves quite a large sector of the population that lives in Harare, Zimbabwe. Based on these results, there is no need for HCV screening but HBV screening prior to ART initiation may be required. -

The University of Zimbabwe College of Health Sciences (UZCHS) is Zimbabwe's premier health professions training institution. However, several concerns were raised during the past decade over the quality of health education at UZCHS. The number of faculty and students declined markedly until 2010, when there was a medical student intake of 147 while the faculty comprised only 122 (39%) of a possible 314 positions. The economic and political crises that the country experienced from 1999 to 2009 compounded the difficulties faced by the institution by limiting the availability of resources. The Medical Education Partnership Initiative funding opportunity has given UZCHS the stimulus to embark on reforms to improve the quality of health education it offers. UZCHS, in partnership with the University of Colorado School of Medicine, the University of Colorado Denver Evaluation Center, and Stanford University, designed the Novel Education Clinical Trainees and Researchers (NECTAR) program to implement a series of health education innovations to meet this challenge. Between 2010 and 2013, innovations that have positively affected the quality of health professions education at UZCHS include the launch of comprehensive faculty development programs and mentored clinical and research programs for postgraduate students. A competency-based curriculum reform process has been initiated, a health professions department has been established, and the Research Support Center has been strengthened, providing critical resources to institutionalize health education and research implementation at the college. A core group of faculty trained in medical education has been assembled, helping to ensure the sustainability of these NECTAR activities.

Introduction & Objectives: Due to the scale up of antiretroviral therapy, increasing numbers of HIV-infected children are living into adolescence. As these children grow and surpass the immediate threat of death, the issue of informing them of their HIV status arises. This study aimed to understand how perinatally-infected adolescents learn about their HIV-status as well as to examine their preferences for the disclosure process., Methods: In-depth interviews were conducted with 31 (14 male, 17 female) perinatally-infected adolescents aged 16-20 at an HIV clinic in Harare, Zimbabwe, and focused on adolescents' experiences of disclosure. In addition, 15 (1 male, 14 female) healthcare workers participated in two focus groups that were centred on healthcare workers' practices surrounding disclosure in the clinic. Purposive sampling was used to recruit participants. A coding frame was developed and major themes were extracted using grounded theory methods., Results: Healthcare workers encouraged caregivers to initiate disclosure in the home environment. However, many adolescents preferred disclosure to take place in the presence of healthcare workers at the clinic because it gave them access to accurate information as well as an environment that made test results seem more credible. Adolescents learned more specific information about living with an HIV-positive status and the meaning of that status from shared experiences among peers at the clinic., Conclusions: HIV-status disclosure to adolescents is distinct from disclosure to younger children and requires tailored, age-appropriate guidelines. Disclosure to this age group in a healthcare setting may help overcome some of the barriers associated with caregivers disclosing in the home environment and make the HIV status seem more credible to an adolescent. The study also highlights the value of peer support among adolescents, which could help reduce the burden of psychosocial care on caregivers and healthcare workers.

Background: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations., Methods: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants., Results: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits., Conclusions: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Background: Long-term survivors of vertically acquired human immunodeficiency virus (HIV) infection are reaching adolescence in large numbers in Africa and are at high risk of delayed diagnosis and chronic complications of untreated HIV infection. Chronic respiratory symptoms are more common than would be anticipated based on the HIV literature., Methods: Consecutive adolescents with presumed vertically acquired HIV attending 2 HIV care clinics in Harare, Zimbabwe, were recruited and assessed with clinical history and examination, CD4 count, pulmonary function tests, Doppler echocardiography, and chest radiography (CXR). Those with suspected nontuberculous chronic lung disease (CLD) were scanned using high-resolution computed tomography (HRCT)., Results: Of 116 participants (43% male; mean age, 14 ± 2.6 years, mean age at HIV diagnosis, 12 years), 69% were receiving antiretroviral therapy. Chronic cough and reduced exercise tolerance were reported by 66% and 21% of participants, respectively; 41% reported multiple respiratory tract infections in the previous year, and 10% were clubbed. More than 40% had hypoxemia at rest (13%) or on exercise (29%), with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) in 7%. Forced expiratory volume in 1 second (FEV(1)) was <80% predicted in 45%, and 47% had subtle CXR abnormalities. The predominant HRCT pattern was decreased attenuation as part of a mosaic attenuation pattern (31 of 56 [55%]), consistent with small airway disease and associated with bronchiectasis (Spearman correlation coefficient (r(2) = 0.8) and reduced FEV(1) (r(2) = -0.26)., Conclusions: Long-term survivors of vertically acquired HIV in Africa are at high risk of a previously undescribed small airway disease, with >40% of unselected adolescent clinic attendees meeting criteria for severe hypoxic CLD. This condition is not obvious at rest. Etiology, prognosis, and response to treatment are currently unknown.

Background: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection., Methods: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing., Results: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated β-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient., Conclusions: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Objectives: We investigated attitudes toward provider-initiated HIV testing and counseling (PITC) in the suburbs of Harare, Zimbabwe, where late presentation after mother-to-child HIV transmission (MTCT) is a major cause of adolescent mortality., Methods: Adolescents (10-18 years) attending 2 primary clinics were offered PITC. Participants completed a questionnaire investigating acceptability of PITC, and in-depth interviews with 41 adolescents and 30 guardians explored understanding of long-term survival after MTCT., Results: Of 506 participants, 16 were known to be HIV-positive; of the remaining 490, only 5 (1%) declined HIV testing. Infected adolescents and their guardians often anticipated a positive result and reported being advised by relatives (but not health workers) to be tested because of chronic illness, especially if parents or siblings had died or were HIV-infected. However, HIV-negative participants were not aware that long-term survival following MTCT could occur. All adolescents felt that HIV diagnosed at their age would be assumed to have been sexually acquired regardless of the true mode of transmission., Conclusions: Including late diagnosis of MTCT in pretest counseling and health educational messages may facilitate PITC for older children and adolescents, especially for those who have not had their sexual debut.

Objective: To present an algorithm for primary-care health workers for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission., Methods: Five hundred and six adolescent (10-18 years) attendees to two primary care clinics in Harare, Zimbabwe, were recruited. A randomly extracted 'training' data set (n = 251) was used to generate an algorithm using variables identified as associated with HIV through multivariable logistic regression. Performance characteristics of the algorithm were evaluated in the remaining ('test') records (n = 255) at different HIV prevalence rates., Results: HIV prevalence was 17%, and infection was independently associated with client-reported orphanhood, past hospitalization, skin problems, presenting with sexually transmitted infection and poor functional ability. Classifying adolescents as requiring HIV testing if they reported >1 of these five criteria had 74% sensitivity and 80% specificity for HIV, with the algorithm correctly predicting the HIV status of 79% of participants. In low-HIV-prevalence settings (<2%), the algorithm would have a high negative predictive value (≥ 99.5%) and result in an estimated 60% decrease in the number of people needing to test to identify one HIV-infected individual, compared with universal testing., Conclusions: Our simple algorithm can identify which individuals are likely to be HIV infected with sufficient accuracy to provide a screening tool for use in settings not already implementing universal testing policies among this age-group, for example immigrants to low-HIV-prevalence countries., (© 2010 Blackwell Publishing Ltd.)