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Introduction: Routine viral load (VL) testing among persons living with Human Immunodeficiency Virus (PLHIV) enables earlier detection of sub-optimal antiretroviral therapy (ART) adherence and for appropriate management of treatment failure. Since adoption of this policy by Zimbabwe in 2016, the extent of implementation is unclear. Therefore we set out to determine among PLHIV ever enrolled on ART from 2004-2017 and in ART care for ≥12 months at health facilities providing ART in Zimbabwe: numbers (proportions) with VL testing uptake, VL suppression and subsequently switched to 2nd-line ART following confirmed virologic failure., Materials and Methods: We used retrospective data from the electronic Patient Monitoring System (ePMS) in which PLHIV on ART are registered at 525 public and 4 private health facilities., Results: Among the 392,832 PLHIV in ART care for ≥12 months, 99,721 (25.4%) had an initial VL test done and results available of whom 81,932 (82%) were virally suppressed. Among those with a VL>1000 copies/mL; 6,689 (37.2%) had a follow-up VL test and 4,086 (61%) had unsuppressed VLs of whom only 1,749 (42.8%) were switched to 2nd-line ART. Lower age particularly adolescents (10-19 years) were more likely (ARR 1.34; 95%CI: 1.25-1.44) to have virologic failure., Conclusion: The study findings provide insights to implementation gaps including limitations in VL testing; low identification of high- risk PLHIV in care and lack of prompt utilization of test results. The use of electronic patient-level data has demonstrated its usefulness in assessing the performance of the national VL testing program. By end of 2017 implementation of VL testing was sub-optimal, and virological failure was relatively common, particularly among adolescents. Of concern is evidence of failure to act on VL test results that were received. A quality improvement initiative has been planned in response to these findings and its effect on patient management will be monitored., Competing Interests: The authors have declared that no competing interests exist.

Zimbabwe has a high burden of HIV (i.e., estimated 1.3 million HIV-infected and 13.8% HIV incidence in 2017). In 2017, the country developed and implemented a pilot of HIV case surveillance (CS) based on the 2017 World Health Organisation (WHO) person-centred HIV patient monitoring (PM) and case surveillance guidelines. At the end of the pilot phase an evaluation was conducted to inform further steps. The pilot was conducted in two districts (i.e., Umzingwane in Matabeleland South Province and Mutare in Manicaland Province) from August 2017 to December 2018. A mixed-methods cross-sectional study of stakeholders and health facility staff was used to assess the design and operations, performance, usefulness, sustainability, and scalability of the CS system. A total of 13 stakeholders responded to an online questionnaire, while 33 health facility respondents were interviewed in 11 health facilities in the two districts. The HIV CS system was adequately designed for Zimbabwe's context, integrated within existing health information systems at the facility level. However, the training was minimal, and an opportunity to train the data entry clerks in data analysis was missed. The system performed well in terms of surveillance and informatics attributes. However, viral load test results return was a significant problem. The HIV CS system was found useful at the health facility level and should be rolled out in a phased manner, beginning in Manicaland and Matabeleland South provinces. An electronic link needs to be made between the health facilities and the laboratory to reduce viral load test results delays., Competing Interests: The authors declare no competing interests., (Copyright: Peter Nsubuga et al.)

Introduction: Index-linked HIV testing, targeted at sexual contacts or children of individuals with HIV, may improve yield and efficiency. The B-GAP study evaluated index-linked testing approaches in health facility and community-based settings. This paper reports on a qualitative study to understand factors that affect uptake of index-linked HIV testing for children and adolescents., Methods: We conducted four focus group discussions (FGDs) with caregivers who had their children tested through B-GAP and one FGD with providers who offered index-linked HIV testing to indexes. We aimed to understand enabling and inhibiting factors in the decision-making process. Translated and transcribed transcripts were read for familiarisation. Following initial coding, analytical memos were written to identify emerging key themes across the data., Results: Our findings showed there was inadequate emphasis on paediatric HIV in routine care which had a negative impact on subsequent uptake of testing for children. Once the decision to test had been made, access to facilities was sometimes challenging and alleviated by community-based testing. A key finding was that HIV testing is not a discrete event but a process that was influenced by relationships with other family members and children themselves. These relationships raised complex issues that could prevent or delay the testing process., Conclusion: There is a need to improve messaging on the importance of HIV testing for children and adolescents and to provide support to caregivers and their families in order to improve testing uptake. Addressing access barriers through the provision of community-based testing and implementing a family-centred approach can optimise index-linked testing.

Background: Since the scale-up of the HIV "Treat All" recommendation, evidence on its real-world effect on predictors of attrition (either death or lost to follow-up) is lacking. We conducted a retrospective study using Zimbabwe ART program data to assess the association between "Treat All" and, patient-mix, programmatic characteristics, retention and predictors of attrition., Methods: We used patient-level data from the electronic patient monitoring system (ePMS) from the nine districts, which piloted the "Treat All" recommendation. We compared patient-mix, programme characteristics, retention and predictors of attrition (lost to follow-up, death or stopping ART) in two cohorts; before (April/May 2016) and after (January/February 2017) "Treat All". Retention was estimated using survival analysis. Predictors of attrition were determined using a multivariable Cox regression model. Interactions were used to assess the change in predictors of attrition before and after "Treat All"., Results: We analysed 3787 patients, 1738 (45.9%) and 2049 (54.1%) started ART before and after "Treat All", respectively. The proportion of men was higher after "Treat All" (39.4.% vs 36.2%, p = 0.044). Same-day ART initiation was more frequent after "Treat All" (43.2% vs 16.4%; p<0.001) than before. Retention on ART was higher before "Treat All" (p<0.001). Among non-pregnant women and men, the adjusted hazard ratio (aHR) of attrition after compared to before "Treat All" was 1.73 (95%CI: 1.30-2.31). The observed hazard of attrition for women being pregnant at ART initiation decreased by 17% (aHR: 1.73*0.48 = 0.83) after "Treat All". Being male (vs female; aHR: 1.45; 95%CI: 1.12-1.87) and WHO Stage IV (vs WHO Stage I-III; aHR: 2.89; 95%CI: 1.16-7.11) predicted attrition both before and after "Treat All" implementation., Conclusion: Attrition was higher after "Treat All"; being male, WHO Stage 4, and pregnancy predicted attrition in both before and after Treat All. However, pregnancy became a less strong risk factor for attrition after "Treat All" implementation., Competing Interests: The authors declare that they have no competing interests.

Introduction: Gutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Médecins Sans Frontières (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities., Methods: A cross-sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged ≥15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV-RNA VL ≥ 1000 copies/mL had Limiting-Antigen-Avidity EIA Assay for cross-sectional estimation of population-level HIV incidence., Results: Among 5439 eligible adults ≥15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI): 12.6 to 14.5). Overall HIV-positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV-positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV-infected participants had a HIV-RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person-years., Conclusions: Our study provides population-level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Adolescents living with HIV (ALHIV) experience a high burden of mental health disorder which is a barrier to antiretroviral therapy adherence. In Zimbabwe, trained, mentored peer supporters living with HIV (Community Adolescent Treatment Supporters - CATS) have been found to improve adherence, viral suppression and psychosocial well-being among ALHIV. The Friendship Bench is the largest integrated mental health programme in Africa. We hypothesise that combining the CATS programme and Friendship Bench will improve mental health and virological suppression among ALHIV compared with the CATS programme alone., Methods: We will conduct a cluster-randomised controlled trial in 60 clinics randomised 1:1 in five provinces. ALHIV attending the control arm clinics will receive standard CATS support and clinic support following the Ministry of Health guidelines. Those attending the intervention arm clinics will receive Friendship Bench problem-solving therapy, delivered by trained CATS. Participants with the signs of psychological distress will be referred to the clinic for further assessment and management. The primary outcome is HIV virological failure (≥1000 copies/ml) or death at 48 weeks. Secondary outcomes include the proportion of adolescents with common mental disorder symptoms (defined as Shona Symptom Questionnaire (SSQ-14) score ≥8), proportion with depression symptoms (defined as Patient Health Questionnaire (PHQ-9) score ≥11), symptom severity (mean SSQ-14 and PHQ-9 scores) and EQ-5D score for health-related quality of life., Conclusions: This trial evaluates the effectiveness of peer-delivery of mental health care on mental health and HIV viral load among ALHIV. If effective this intervention has the potential to be scaled-up to improve these outcomes.Trial registration: PACTR201810756862405. 08 October 2018., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2020.)

Introduction: Multimonth dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. However, randomized evidence of its clinical effectiveness is lacking. We compared MMD within community ART refill groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe., Methods: A three-arm, cluster-randomized, pragmatic noninferiority trial was performed. Thirty health care facilities and associated CARGs were allocated to either ART collected three-monthly at facility (3MF, control); ART delivered three-monthly in CARGs (3MC); or ART delivered six-monthly in CARGs (6MC). Stable adults receiving ART ≥six months with baseline viral load (VL) <1000 copies/ml were eligible. Retention in ART care (primary outcome) and viral suppression (VS) 12 months after enrollment were compared, using regression models specified for clustering (ClinicalTrials.gov: NCT03238846)., Results: 4800 participants were recruited, 1919, 1335, and 1546 in arms 3MF, 3MC, and 6MC, respectively. For retention, the prespecified noninferiority limit (-3.25%, risk difference [RD]) was met for comparisons between all arms, 3MC (94.8%) vs. 3MF (93.0%), adjusted RD = 1.1% (95% CI: -0.5% to 2.8%); 6MC (95.5%) vs. 3MF: aRD = 1.2% (95% CI: -1.0% to 3.6%); and 6MC vs. 3MC: aRD = 0.1% (95% CI: -2.4% to 2.6%). VL completion at 12 months was 49%, 45%, and 8% in 3MF, 3MC, and 6MC, respectively. VS in 3MC (99.7%) was high and not different to 3MF (99.1%), relative risk = 1.0 (95% CI: 1.0-1.0). VS was marginally reduced in 6MC (92.9%) vs. 3MF, relative risk = 0.9 (95% CI: 0.9-1.0)., Conclusion: Retention in CARGs receiving three- and six-monthly MMD was noninferior versus standard-of-care facility-based ART delivery. VS in 3MC was high. VS in six-monthly CARGs requires further evaluation.

Background: In Zimbabwe, Harare was the first province to implement "Treat All" for people living with human immunodeficiency virus (PLHIV). Since its roll out in July 2016, no study has been conducted to assess the changes in key programme indicators. We compared antiretroviral therapy (ART) uptake, time to ART initiation from diagnosis, and retention before and during "Treat All". Methods: We conducted an ecological study to assess ART uptake among all PLHIV newly diagnosed before and during "Treat All". We conducted a cohort study to assess time to ART initiation and retention in care among all PLHIV newly initiated on ART from all electronic patient management system-supported sites (n=50) before and during "Treat All". Results: ART uptake increased from 65% (n=4619) by the end of quarter one, 2014 to 85% (n=5152) by the end of quarter four, 2018.  A cohort of 2289 PLHIV were newly initiated on ART before (April-June 2015) and 1682 during "Treat all" (April-June 2017). Their age and gender distribution was similar. The proportion of PLHIV in early stages of disease was significantly higher during "Treat all" (73.2% vs. 55.6%, p<0.001). The median time to ART initiation was significantly lower during "Treat All" (31 vs. 88 days, p<0.001). Cummulative retention at three, six and 12 months was consistently lower during "Treat all" and was significant at six months (74.9% vs.78.1% p=0.022). Conclusion: Although there were benefits of early ART initiation during "Treat All", the programme should consider strategies to improve retention., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Matare T et al.)

Objectives: Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are known to have a tuberculosis (TB) protective effect at the individual level among people living with HIV (PLHIV). In Zimbabwe where TB is driven by HIV infection, we have assessed whether there is a population-level association between IPT and ART scale-up and annual TB case notification rates (CNRs) from 2000 to 2018., Design: Ecological study using aggregate national data., Setting: Annual aggregate national data on TB case notification rates (stratified by TB category and type of disease), numbers (and proportions) of PLHIV in ART care and of these, numbers (and proportions) ever commenced on IPT., Results: ART coverage in the public sector increased from <1% (8400 PLHIV) in 2004 to ~88% (>1.1 million PLHIV patients) by December 2018, while IPT coverage among PLHIV in ART care increased from <1% (98 PLHIV) in 2012 to ~33% (373 917 PLHIV) by December 2018. These HIV-related interventions were associated with significant declines in TB CNRs: between the highest CNR prior to national roll-out of ART (in 2004) to the lowest recorded CNR after national IPT roll-out from 2012, these were (1) for all TB case (510 to 173 cases/100 000 population; 66% decline, p<0.001); (2) for those with new TB (501 to 159 cases/100 000 population; 68% decline, p<0.001) and (3) for those with new clinically diagnosed PTB (284 to 63 cases/100 000 population; 77.8% decline, p<0.001)., Conclusions: This study shows the population-level impact of the continued scale-up of ART among PLHIV and the national roll-out of IPT among those in ART care in reducing TB, particularly clinically diagnosed TB which is largely associated with HIV. There are further opportunities for continued mitigation of TB with increasing coverage of ART and in particular IPT which still has a low coverage., Competing Interests: Competing interests: Technical support was provided through the International Union Against Tuberculosis and Lung Disease (IUATLD). Kudakwashe Takarinda is supported as a Senior Operations Research Fellow from the Centre for Operational Research at the IUATLD, Paris, France., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Zimbabwe is one of the countries in sub-Saharan Africa disproportionately affected by human immunodeficiency virus. In the "treat all" era, we assessed the gaps in routine viral load (VL) monitoring at six months for children (0-9 years) and adolescents (10-19 years) newly initiated on anti-retroviral therapy (ART) from January 2017 to September 2018 at a large tertiary hospital in Bulawayo. Methods: In this cohort study using secondary data, we considered first VL done within six to nine months of starting therapy as 'undergoing VL test at six months'. We classified repeat VL≥1000 copies/ml despite enhanced adherence counselling as virally unsuppressed. Results: Of 295 patients initiated on ART, 196 (66%) were children and 99 (34%) adolescents. A total 244 (83%) underwent VL test at six months, with 161 (54%) virally suppressed, 52 (18%) unsuppressed and 82 (28%) with unknown status (due to losses in the cascade). Switch to second line was seen in 35% (18/52). When compared to children, adolescents were less likely to undergo a VL test at six months (73% versus 88%, p=0.002) and more likely to have an unknown VL status (40% versus 22%, p=0.001). Conclusion: At six months of ART, viral suppression was low and losses in the cascade high., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Moyo S et al.)

Background: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens., Methods: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted., Findings: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain., Interpretation: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators., Funding: Bill & Melinda Gates Foundation., (Copyright © 2020 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.)

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services., Competing Interests: The authors have declared that no competing interests exist. SR is a member of the Editorial Board of PLOS Medicine. EG is an academic editor at PLOS Medicine.

Background: Adolescents living with HIV face challenges to their wellbeing and antiretroviral therapy adherence and have poor treatment outcomes. We aimed to evaluate a peer-led differentiated service delivery intervention on HIV clinical and psychosocial outcomes among adolescents with HIV in Zimbabwe., Methods: 16 public primary care facilities (clusters) in two rural districts in Zimbabwe (Bindura and Shamva) were randomly assigned (1:1) to provide enhanced HIV care support (the Zvandiri intervention group) or standard HIV care (the control group) to adolescents (aged 13-19 years) with HIV. Eligible clinics had at least 20 adolescents in pre-ART or ART registers and were geographically separated by at least 10 km to minimise contamination. Adolescents were eligible for inclusion if they were living with HIV, registered for HIV care at one of the trial clinics, and either starting or already on ART. Exclusion criteria were being too physically unwell to attend clinic (bedridden), psychotic, or unable to give informed assent or consent. Adolescents with HIV at all clinics received adherence support through adult counsellors. At intervention clinics, adolescents with HIV were assigned a community adolescent treatment supporter, attended a monthly support group, and received text messages, calls, home visits, and clinic-based counselling. Implementation intensity was differentiated according to each adolescent's HIV vulnerability, which was reassessed every 3 months. Caregivers were invited to a support group. The primary outcome was the proportion of adolescents who had died or had a viral load of at least 1000 copies per μL after 96 weeks. In-depth qualitative data were collected and analysed thematically. The trial is registered with Pan African Clinical Trial Registry, number PACTR201609001767322., Findings: Between Aug 15, 2016, and March 31, 2017, 500 adolescents with HIV were enrolled, of whom four were excluded after group assignment owing to testing HIV negative. Of the remaining 496 adolescents, 212 were recruited at Zvandiri intervention sites and 284 at control sites. At enrolment, the median age was 15 years (IQR 14-17), 52% of adolescents were female, 81% were orphans, and 47% had a viral load of at least 1000 copies per μL. 479 (97%) had primary outcome data at endline, including 28 who died. At 96 weeks, 52 (25%) of 209 adolescents in the Zvandiri intervention group and 97 (36%) of 270 adolescents in the control group had an HIV viral load of at least 1000 copies per μL or had died (adjusted prevalence ratio 0·58, 95% CI 0·36-0·94; p=0·03). Qualitative data suggested that the multiple intervention components acted synergistically to improve the relational context in which adolescents with HIV live, supporting their improved adherence. No adverse events were judged to be related to study procedures. Severe adverse events were 28 deaths (17 in the Zvandiri intervention group, 11 in the control group) and 57 admissions to hospital (20 in the Zvandiri intervention group, 37 in the control group)., Interpretation: Peer-supported community-based differentiated service delivery can substantially improve HIV virological suppression in adolescents with HIV and should be scaled up to reduce their high rates of morbidity and mortality., Funding: Positive Action for Adolescents Program, ViiV Healthcare., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Zimbabwe is scaling up HIV differentiated service delivery (DSD) to improve treatment outcomes and health system efficiencies. Shifting stable patients into less-intensive DSD models is a high priority in order to accommodate the large numbers of newly-diagnosed people living with HIV (PLHIV) needing treatment and to provide healthcare workers with the time and space needed to treat people with advanced HIV disease. DSD is also seen as a way to improve service quality and enhance retention in care. National guidelines support five differentiated antiretroviral treatment models (DART) for stable HIV-positive adults, but little is known about patient preferences, a critical element needed to guide DART scale-up and ensure person-centered care. We designed a mixed-methods study to explore treatment preferences of PLHIV in urban Zimbabwe., Methods: The study was conducted in Harare, and included 35 health care worker (HCW) key informant interviews (KII); 8 focus group discussions (FGD) with 54 PLHIV; a discrete choice experiment (DCE) in which 500 adult DART-eligible PLHIV selected their preferences for health facility (HF) vs. community location, individual vs. group meetings, provider cadre and attitude, clinic operation times, visit frequency, visit duration and cost to patient; and a survey with the 500 DCE participants exploring DART knowledge and preferences., Results: Patient preferences were consistent in the FGDs, DCE and survey. Participants strongly preferred respectful HCWs, HF-based services, individual DART models, and less costly services. Patients also preferred less frequent visits and shorter wait times. They were indifferent to variations in HCW cadre and distances from home to HF. These preferences were mostly homogenous, with only minor differences between male vs. female and older vs. younger patients. HCWs in the KII correctly characterized facility-based individual models as the one most favored by patients; HCWs also preferred this model, which they felt decongested HFs and reduced their workload., Conclusions: DART-eligible PLHIV in Harare found it relatively easy to access HFs, and preferred attributes associated with facility-based individual models. Prioritizing these for scale-up in urban areas may be the most efficient way to sustain positive patient outcomes and increase health system performance., Competing Interests: The authors have declared that no competing interests exist.

Background: The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow-up evaluation for the 2012-2015 cohorts to assess the implementation and impact of recommendations from this prior evaluation., Methods: A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LTFU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model., Results: A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4% (p-value = 0.060), 86.5% (p-value<0.001), 79.2% (p-value<0.001) and 74.4% (p-value<0.001) at 6, 12, 24 and 36 months respectively. LTFU accounted for 98% of attrition. Being an adolescent or a young adult (15-24 years) (vs adult;1.41; 95% CI:1.14-1.74), children (<15years) (vs adults; aHR 0.64; 95% CI:0.46-0.91), receiving care at primary health care facility (vs central and provincial facility; aHR 1.23; 95% CI:1.01-1.49), having initiated ART between 2014-2015 (vs 2012-2013; aHR1.45; 95%CI:1.24-1.69), having WHO Stage IV (vs Stage I-III; aHR2.06; 95%CI:1.51-2.81) and impaired functional status (vs normal status; aHR1.25; 95%CI:1.04-1.49) predicted attrition., Conclusion: The overall retention was higher in comparison to the previous 2007-2010 evaluation. Further studies to understand why attrition was found to be higher at primary health care facilities are warranted. Implementation of strategies for managing patients with advanced HIV disease, differentiated care for adolescents and young adults and tracking of LTFU clients should be prioritised to further improve retention., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Guidelines for antiretroviral therapy recommend enhanced adherence counselling be provided to individuals with an initial elevated viral load before making a decision whether to switch antiretroviral regimen. We undertook this systematic review to estimate the proportion of patients with an initial elevated viral load who resuppress following enhanced adherence counselling., Methods: Two databases and two conference abstract sites were searched from January 2012 to October 2019 for studies reporting the number of patients with an elevated viral load whose viral load was undetectable when subsequently assessed. Data were pooled using random effects meta-analysis., Results: Fifty-eight studies reported outcomes of 45,720 viraemic patients, mostly from Africa (48 studies), and among patients on first-line antiretroviral therapy (43 studies). Almost half (46.1%, 95% CI 42.6% to 49.5%) of patients with an initial elevated viral load resuppressed following an enhanced adherence intervention. Of those on first-line ART with confirmed virological failure (6280 patients, 21 studies), only 53.4% (40.1% to 66.8%) were appropriately switched to a different regimen. Resuppression was higher among studies that provided details of adherence support. The proportion resuppressing was lower among children (31.2%, 21.1% to 41.3%) and adolescents (40.4%, 15.7% to 65.2%) compared to adults (50.4%, 42.6% to 58.3%). No important differences were observed by date of study publication, gender, viral failure threshold, publication status, time between viral loads or treatment regimen. Information on resistance testing among people with an elevated viral load was inconsistently reported., Conclusions: The findings of this review suggest that in settings with limited resources, current guideline recommendations to provide enhanced adherence counselling can result in resuppression of a substantial number of these patients, avoiding unnecessary drug regimen changes. Appropriate action on viral load results is limited across a range of settings, highlighting the importance of viral load cascade analyses to identify gaps and focus quality improvement to ensure that action is taken on the results of viral load testing., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Suboptimal male engagement in HIV programmes is a persistent challenge, leading to lower coverage of HIV testing, prevention and treatment services, and to worse outcomes for men. Differentiated service delivery models, such as peer-led community antiretroviral refill groups (CARGs), offer the opportunity to enhance patient satisfaction, retention and treatment outcomes. We conducted an exploratory qualitative study to identify facilitators and barriers to CARG participation by HIV-positive men, with inputs from recipients of HIV care, community members, healthcare workers (HCWs), donors and policymakers., Methods: Between July and October 2017, we conducted 20 focus group discussions (FGDs) with 147 adults living with HIV, including men and women enrolled in CARGs and men not enrolled in CARGs, and 46 key informant interviews (KIIs) with policymakers, donors, HCWs and community members. FGDs and KIIs were recorded, transcribed and translated. A constant comparison approach was used to triangulate findings and identify themes related to male engagement in CARGs in rural Zimbabwe., Results: CARG participants, policymakers, donors, HCWs, and community members noted many advantages to CARG participation, including convenience, efficiency, solidarity and mutual psychosocial support. Although those familiar with CARGs reported that these groups decreased HIV-related stigma, concerns about stigma and privacy were perceived to be the primary reason for men's non-participation. Other important barriers to male enrolment included lack of awareness of CARGs, misunderstanding of how CARGs operate, few perceived benefits and lack of flexibility in CARG implementation., Conclusions: More effective educational and awareness campaigns, community-based anti-stigma campaigns, more flexible CARG designs, and provision of financial and/or in-kind support to CARG members could mitigate many of the barriers to male enrolment in CARGs. Men may also prefer alternative differentiated service delivery models that are facility-based and/or do not require group participation., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Community ART Refill Groups (CARGs) are an antiretroviral therapy (ART) delivery model where clients voluntarily form into groups, and a group member visits the clinic to collect ART for all group members. In late 2016, Zimbabwe began a nationwide rollout of the CARG model. We conducted a qualitative evaluation to assess the perceived effects of this new national service delivery model., Methods: In March-June 2018, we visited ten clinics implementing the CARG model across five provinces of Zimbabwe and conducted a focus group discussion with healthcare workers and in-depth interviews with three ART clients per clinic. Clinics had implemented the CARG model for approximately one year. All discussions were audio recorded, transcribed, and translated into English, and thematic coding was performed by two independent analysts., Results: In focus groups, healthcare workers described that CARGs made ART distribution faster and facilitated client tracking in the community. They explained that their reduced workload allowed them to provide better care to those clients who did visit the clinic, and they felt that the CARG model should be sustained in the future. CARG members reported that by decreasing the frequency of clinic visits, CARGs saved them time and money, reducing previous barriers to collecting ART and improving adherence. CARG members also valued the emotional and informational support that they received from other members of their CARG, further improving adherence. Multiple healthcare workers did express concern that CARG members with diseases that begin with minor symptoms, such as tuberculosis, may not seek treatment at the clinic until the disease has progressed., Conclusions: We found that healthcare workers and clients overwhelmingly perceive CARGs as beneficial. This evaluation demonstrates that the CARG model can be successfully implemented on a national scale. These early results suggest that CARGs may be able to simultaneously improve clinical outcomes and reduce the workload of healthcare workers distributing ART., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: The number of new paediatric infections per year has declined in sub-Saharan Africa due to prevention-of-mother-to-child HIV transmission programmes; many children and adolescents living with HIV remain undiagnosed. In this protocol paper, we describe the methodology for evaluating an index-linked HIV testing approach for children aged 2-18 years in health facility and community settings in Zimbabwe., Methods and Analysis: Individuals attending for HIV care at selected primary healthcare clinics (PHCs) will be asked if they have any children aged 2-18 years in their households who have not been tested for HIV. Three options for HIV testing for these children will be offered: testing at the PHC; home-based testing performed by community workers; or an oral mucosal HIV test given to the caregiver to test the children at home. All eligible children will be followed-up to ascertain whether HIV testing occurred. For those who did not test, reasons will be determined, and for those who tested, the HIV test result will be recorded. The primary outcome will be uptake of HIV testing. The secondary outcomes will be preferred HIV testing method, HIV yield, prevalence and proportion of those testing positive linking to care and having an undetectable viral load at 12 months. HIV test results will be stratified by sex and age group, and factors associated with uptake of HIV testing and choice of HIV testing method will be investigated., Ethics and Dissemination: Ethical approval for this study was granted by the Medical Research Council of Zimbabwe, the London School of Hygiene and Tropical Medicine and the Institutional Review Board of the Biomedical Research and Training Institute. Study results will be presented at national policy meetings and national and international research conferences. Results will also be published in international peer-reviewed scientific journals and disseminated to study communities at the end of study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric., Methods: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars)., Results: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum., Conclusions: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Expansion of provider-initiated testing and counselling (PITC) is one strategy to increase accessibility of HIV testing services. Insufficient human resources was identified as a primary barrier to increasing PITC coverage in Zimbabwe. We evaluated if deployment of supplemental PITC providers at public facilities in Zimbabwe was associated with increased numbers of individuals tested and diagnosed with HIV., Methods: From July 2016 to May 2017, International Training and Education Center for Health (I-TECH) deployed 138 PITC providers to supplement existing ministry healthcare workers offering PITC at 249 facilities. These supplemental providers were assigned to facilities on a weekly basis. Each week, I-TECH providers reported the number of HIV tests and positive diagnoses they performed. Using routine reporting systems, we obtained from each facility the number of clients tested and diagnosed with HIV per month. Including data both before and during the intervention period, and utilizing the weekly variability in placement locations of the supplemental PITC providers, we employed generalized estimating equations to assess if the placement of supplemental PITC providers at a facility was associated with a change in facility outputs., Results: Supplemental PITC providers performed an average of 62 (SD = 52) HIV tests per week and diagnosed 4.4 (SD = 4.9) individuals with HIV per week. However, using facility reports from the same period, we found that each person-week of PITC provider deployment at a facility was associated with an additional 16.7 (95% CI, 12.2-21.1) individuals tested and an additional 0.9 (95% CI, 0.5-1.2) individuals diagnosed with HIV. We also found that staff placement at clinics was associated with a larger increase in HIV testing than staff placement at polyclinics or hospitals (24.0 vs. 9.8; p < 0.001)., Conclusions: This program resulted in increased numbers of individuals tested and diagnosed with HIV. The discrepancy between the average weekly HIV tests conducted by supplemental PITC providers (62) and the increase in facility-level HIV tests associated with one week of PITC provider deployment (16.7) suggests that supplemental PITC providers displaced existing staff who may have been reassigned to fulfil other duties at the facility.

Background: In people living with HIV (PLHIV) who are on anti-retroviral therapy (ART), it is essential to identify persons with high blood viral loads (VLs) (≥1000 copies/ml), provide enhanced adherence counselling (EAC) for 3 months and assess for VL suppression (<1000 copies/ml)., Objective: Our study objectives were to determine the proportion who had a high viral load in those people who underwent viral load testing between 1 August 2016-31 July 2017 at Wilkins Hospital, Harare, Zimbabwe. Of those with high viral load to assess; a) the proportion who enrolled for EAC, the demographic and clinical characteristics associated with enrolment for EAC and, b) the proportion who achieved viral load suppression and demographic, clinical characteristics associated with viral load suppression., Design: Retrospective cohort study using routinely collected programme data. Data was collected from PLHIV who were on ART and had a high viral load from 1 August 2016 to 31 July 2017., Results: Of 5,573 PLHIV on ART between 1 August 2016 and 31 July 2017, 4787 (85.9%) had undergone VL testing and 646 (13.5%) had high VLs. Of these 646, only 489 (75.7%) were enrolled for EAC, of whom 444 (69%) underwent a repeat VL test at ≥ 3 months with 201 (31.2%) achieving VL suppression. The clinical characteristics that were independently associated with higher probability of VL suppression were: a) undergoing 3 sessions of EAC; b) being on 2nd line ART. Initial VL levels >5,000 copies/ml were associated with lower probability of viral suppression., Conclusion: The routine VL testing levels were high, but there were major programmatic gaps in enrolling PLHIV with high VLs into EAC and achieving VL suppression. The full potential of EAC on achieving viral load suppression has not been achieved in this setting. The reasons for these gaps need to be assessed in future research studies and addressed by suitable changes in policies/practices., Competing Interests: The authors have declared that no competing interests exist.

Background: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains., Methods: We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted., Findings: The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving., Interpretation: Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2019 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.)

Introduction: Heat-stable lopinavir/ritonavir (LPV/r) oral pellets were developed to overcome challenges with administration and storage experienced with previously available tablet and syrup forms of LPV/r prescribed to paediatric HIV patients. We report on the adoption of LPV/r pellets for infants living with HIV in the public sector antiretroviral therapy (ART) programme in Zimbabwe., Methods: Infants aged three months to three years who had been prescribed a LPV/r-based regimen (including ART-naïve patients) in fourteen facilities across the country were eligible to receive the pellets. Caregivers were counselled on the new formulation and provided with administration guides. A caregiver questionnaire was administered three to four months after the child initiated on pellets. Data were also extracted from patient ART records., Results and Discussion: One hundred and fifty-seven children were enrolled (median age: 21 months; interquartile range 11.8 to 29.4). Survey data from 74 caregivers were included for analysis. Eighty-one per cent of the caregivers preferred pellets while 19% preferred the syrup formulation. Eighty-nine per cent assessed their child's response to taking the pellets as good or very good. Overall, 46% did not report any challenges while 54% reported one or more challenges with using the pellets. Difficulties with administration included: poor taste (36%; 26 participants); swallowing pellets (16%; 12 participants); finishing the dose (14%; 10 participants); and opening the capsule (10%; seven participants). Caregivers who were not confident to instruct others on pellet administration were 5.64 (95% confidence interval 1.45 to 21.95, p = 0.013) times as likely to experience a challenge., Conclusions: A large proportion of caregivers preferred pellets to other formulations of LPV/r and reported a good response to pellets; however, they also reported challenges with administration. Counselling should focus on ensuring that caregivers can confidently administer pellets and are able to instruct others, to ensure high uptake and good adherence to treatment. LPV/r pellets may be an acceptable substitute for other available forms of LPV/r for eligible children under three years if they are currently on or in need of LPV/r-containing regimens; however, challenges with administration still highlight the need for improved drug formulations for paediatric ART patients., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: The 90-90-90 targets set by the United Nations aspire to 73% of people living with HIV (PLHIV) being virally suppressed by 2020. Using the HIV Synthesis Model, we aim to mimic the epidemic in Zimbabwe and make projections to assess whether Zimbabwe is on track to meet the 90-90-90 targets and assess whether recently proposed UNAIDS HIV transition metrics are likely to be met., Methods: We used an approximate Bayesian computation approach to identify model parameter values which result in model outputs consistent with observed data, evaluated using a calibration score. These parameter values were then used to make projections to 2020 to compare with the 90-90-90 targets and other key indicators. We also calculated HIV transition metrics proposed by UNAIDS (percentage reduction in new HIV infections and AIDS-related mortality from 2010 to 2020, absolute rate of new infections and AIDS-related mortality, incidence-mortality ratio and incidence-prevalence ratios)., Results: After calibration, there was general agreement between modelled and observed data. The median predicted outcomes in 2020 were: proportion of PLHIV (aged 15 to 65) diagnosed 0.91 (90% uncertainty range 0.87, 0.94) (0.84 men, 0.95 women); of those diagnosed, proportion on treatment 0.92 (0.90, 0.93); of those receiving treatment, proportion with viral suppression 0.86 (0.81, 0.91). This results in 72% of PLHIV having viral suppression in 2020. We estimated a percentage reduction of 36.5% (13.7% increase to 67.4% reduction) in new infections from 2010 to 2020, and of 30.4% (9.7% increase to 56.6% reduction) in AIDS-related mortality (UNAIDS target 75%). The modelled absolute rates of HIV incidence and AIDS-related mortality in 2020 were 5.48 (2.26, 9.24) and 1.93 (1.31, 2.71) per 1000 person-years respectively. The modelled incidence-mortality ratio and incidence-prevalence ratios in 2020 were 1.05 (0.46, 1.66) and 0.009 (0.004, 0.013) respectively., Conclusions: Our model was able to produce outputs that are simultaneously consistent with an array of observed data and predicted that while the 90-90-90 targets are within reach in Zimbabwe, increased efforts are required in diagnosing men in particular. Calculation of the HIV transition metrics suggest increased efforts are needed to bring the HIV epidemic under control., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Intensified TB case finding is recommended for all HIV-infected persons regularly attending HIV care and treatment clinics. The authors aimed to determine how well this system worked among HIV-infected patients diagnosed with presumptive TB in 14 health facilities of Harare province, Zimbabwe, between January and December 2016., Methods: Retrospective review using routine programme records., Results: Of 47 659 HIV-infected persons enrolled in HIV care, 102 were identified with presumptive TB through the programmatic electronic database. Of these, 23% (23/102) were recorded in presumptive TB registers and, of these 65% (15/23) were traced to laboratory registers. Of 79 patients not recorded in presumptive TB registers, 9% (7/79) were traced to laboratory registers. Of 22 patients in the laboratory register, all had negative sputum smears for acid-fast bacilli and 45% (10/22) had Xpert MTB/RIF assays with one positive result. Six patients altogether started anti-tuberculosis treatment, the median time from presumptive tuberculosis diagnosis to treatment being 12 days. The only significant risk factor for loss-to-follow-up between presumptive TB diagnosis and laboratory registration was not being recorded in presumptive TB registers., Conclusions: Follow-up mechanisms for presumptive TB cases diagnosed in HIV care clinics in Harare city need strengthening, particularly through improved documentation in presumptive TB registers and better Xpert MTB/RIF use.

Since 2004, there has been a dramatic shift in the HIV response for children, adolescents, and young people in low resource settings. Previous programs and services were largely orientated to adults. This is now changing, but there is limited evidence on how to take services for children, adolescents, and young people living with HIV (CAYPLHIV) to scale. Zvandiri is a theoretically grounded, multicomponent-differentiated service delivery model for children, adolescents, and young people in Zimbabwe that integrates peer-led, community interventions within government health services. Africaid analyzed routine program and other data from November 2004 to October 2017 to document Zvandiri scale-up, framed by the World Health Organization framework for scaling up interventions. Since 2004, Zvandiri has evolved from one support group in Harare into a comprehensive model, combining community- and clinic-based health services and psychosocial support for CAYPLHIV. Zvandiri was scaled up across Zimbabwe through phased expansion into 51 of 63 districts, reaching 40,213 CAYPLHIV. Evidence indicates that this approach improved uptake of HIV testing services, adherence, and retention in care. The environment and strategic choices were critical when taking the model to scale, particularly nesting the program within existing services, and capacity strengthening of service providers working jointly with trained, mentored CAYPLHIV. The results provide a firm foundation for programming and from which to build evidence of sustainable impact. Formal impact evaluation is needed and underway. These program data contribute to the essential evidence base on strategic approaches to assist in planning services for this relatively neglected group.

Background: There is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high., Methods: The HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year., Findings: A transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost., Interpretation: A future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance., Funding: Bill & Melinda Gates Foundation, World Health Organization., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY IGO 3.0 licence. Published by Elsevier Ltd.. All rights reserved.)

Background: Sub-Saharan Africa is the world region with the greatest number of people eligible to receive antiretroviral treatment (ART). Less frequent dispensing of ART and community-based ART-delivery models are potential strategies to reduce the load on overburdened healthcare facilities and reduce the barriers for patients to access treatment. However, no large-scale trials have been conducted investigating patient outcomes or evaluating the cost-effectiveness of extended ART-dispensing intervals within community ART-delivery models. This trial will assess the clinical effectiveness, cost-effectiveness and acceptability of providing ART refills on a 3 vs. a 6-monthly basis within community ART-refill groups (CARGs) for stable patients in Zimbabwe., Methods: In this pragmatic, three-arm, parallel, unblinded, cluster-randomized non-inferiority trial, 30 clusters (healthcare facilities and associated CARGs) are allocated using stratified randomization in a 1:1:1 ratio to either (1) ART refills supplied 3-monthly from the health facility (control arm), (2) ART refills supplied 3-monthly within CARGs, or (3) ART refills supplied 6-monthly within CARGs. A CARG consists of 6-12 stable patients who meet in the community to receive ART refills and who provide support to one another. Stable adult ART patients with a baseline viral load < 1000 copies/ml will be invited to participate (1920 participants per arm). The primary outcome is the proportion of participants alive and retained in care 12 months after enrollment. Secondary outcomes (measured at 12 and 24 months) are the proportions achieving virological suppression, average provider cost per participant, provider cost per participant retained, cost per participant retained with virological suppression, and average patient-level costs to access treatment. Qualitative research will assess the acceptability of extended ART-dispensing intervals within CARGs to both providers and patients, and indicators of potential facility-level decongestion due to the interventions will be assessed., Discussion: Cost-effective health system models that sustain high levels of patient retention are urgently needed to accommodate the large numbers of stable ART patients in sub-Saharan Africa. This will be the first trial to evaluate extended ART-dispensing intervals within a community-based ART distribution model, and results are intended to inform national and regional policy regarding their potential benefits to both the healthcare system and patients., Trial Registration: ClinicalTrials.gov, ID: NCT03238846 . Registered on 27 July 2017.

Background: World Health Organization (WHO) adolescent HIV-testing and treatment guidelines recommend community-based interventions to support antiretroviral therapy (ART) adherence and retention in care, while acknowledging that the evidence to support this recommendation is weak. This cluster randomized controlled trial aims to evaluate the effectiveness and cost-effectiveness of a psychosocial, community-based intervention on HIV-related and psychosocial outcomes., Methods/design: We are conducting the trial in two districts. Sixteen clinics were randomized to either enhanced ART-adherence support or standard of care. Eligible individuals (HIV-positive adolescents aged 13-19 years and eligible for ART) in both arms receive ART and adherence support provided by adult counselors and nursing staff. Adolescents in the intervention arm additionally attend a monthly support group, are allocated to a designated community adolescent treatment supporter, and followed up through a short message service (SMS) and calls plus home visits. The type and frequency of contact is determined by whether the adolescent is "stable" or in need of enhanced support. Stable adolescents receive a monthly home visit plus a weekly, individualized SMS. An additional home visit is conducted if participants miss a scheduled clinic appointment or support-group meeting. Participants in need of further, enhanced, support receive bi-weekly home visits, weekly phone calls and daily SMS. Caregivers of adolescents in the intervention arm attend a caregiver support group. Trial outcomes are assessed through a clinical, behavioral and psychological assessment conducted at baseline and after 48 and 96 weeks. The primary outcome is the proportion who have died or have virological failure (viral load ≥1000 copies/ml) at 96 weeks. Secondary outcomes include virological failure at 48 weeks, retention in care (proportion of missed visits) and psychosocial outcomes at both time points. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cluster randomized trials, including a flowchart., Discussion: This study provides a unique opportunity to generate evidence of the impact of the on-going Zvandiri program, for adolescents living with HIV, on virological failure and psychosocial outcomes as delivered in a real-world setting. If found to reduce rates of treatment failure, this would strengthen support for further scale-up across Zimbabwe and likely the region more widely., Trial Registration: Pan African Clinical Trial Registry database, registration number PACTR201609001767322 (the Zvandiri trial). Retrospectively registered on 5 September 2016.

Background: Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe., Methods and Findings: Over the course of 2 years (January 2013-January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a representative cross-sectional survey of 8-17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7,146 children in 4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2,643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect., Conclusions: Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

Introduction: Expanding and sustaining antiretroviral therapy (ART) coverage may require simplified HIV service delivery strategies that concomitantly reduce the burden of care on the health system and patients while ensuring optimal outcomes. We conducted a systematic review to assess the impact of reduced frequency of clinic visits and drug dispensing on patient outcomes., Methods: As part of the development process of the World Health Organization antiretroviral (ARV) guidelines, we systematically searched medical literature databases for publications up to 30 August 2016. Information was extracted on trial characteristics, patient characteristics and the following outcomes: mortality, morbidity, treatment adherence, retention, patient and provider acceptability, cost and patients exiting the programme. When feasible, conventional pairwise meta-analyses were conducted. Results and discussion Of 6443 identified citations, 21 papers, pertaining to 16 studies, were included in this review, with 11 studies contributing to analyses. Although analyses were feasible, they were limited by the sparse evidence base, despite the importance of the research area, and relatively low quality. Comparative analyses of eight studies reporting on frequency of clinic visits showed that less frequent clinic visits led to higher odds of being retained in care (odds ratio [OR]: 1.90; 95% CI: 1.21-2.99). No differences were found with respect to viral failure, morbidity or mortality; however, most estimates were favourable to reduced clinic visits. Reduced frequency of ARVs pick-ups showed a trend towards better retention (OR: 1.93; 95% CI: 0.62-6.04). Strategies using community support tended to have better outcomes; however, their implementation varied, particularly by location. External validity may be questionable., Conclusions: Our systematic review suggests that reduction of clinical visits (and likely ARVs pick-ups) may improve clinical outcomes, and that they are a viable option to relieve health systems and reduce burden of care for PLHIV. Strategies aimed at reducing clinic visits or drug refill services should focus on stable patients who are virally suppressed, tolerant to their drug regimen and fully adherent. These strategies may be critical to the current changes taking place in HIV treatment policy; thus, due to the data limitations, further high quality research is needed to inform policy and programmatic interventions., Competing Interests: We declare that we have no conflicts of interest.

Introduction: Globally, increasing numbers of HIV-infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss-to-follow-up (LTFU) from HIV care services among children as they transition from childhood through adolescence., Methods: Individuals aged 5-19 years initiated on ART in a public-sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age-bands namely: 5-9 (children), 10-14 (young adolescents) and 15-19 (older adolescents). The effect of age at ART initiation, current age (using a time-updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression., Results: Of 2273 participants, 1013, 875 and 385 initiated ART aged 5-9, 10-14 and 15-19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age-band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94-2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05-3.07). In older adolescents, the LTFU rate among those who started ART in that age-band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age-groups., Conclusions: Adolescents had higher rates of LTFU compared to other age-groups, with older adolescents at particularly high risk in all analyses. Age-updated analyses that examine movement across narrow age-bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes., Competing Interests: The authors have no competing interests.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.* , † , § To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Background: Age-specific retention challenges make antiretroviral therapy (ART) initiation in adolescents difficult, often requiring a lengthy preparation process. This needs to be balanced against the benefits of starting treatment quickly. The optimal time to initiation duration in adolescents is currently unknown., Objective: To assess the effect of time to ART initiation on mortality and loss to follow-up (LTFU) among treatment eligible adolescents., Methods: We conducted a retrospective cohort analysis among 1499 ART eligible adolescents aged ≥10 to <19 years registered in a public sector HIV program in Bulawayo, Zimbabwe, between 2004 and 2011. Hazard ratios (HR) for mortality and LTFU were calculated for different time to ART durations using multivariate Cox regression models., Results: Median follow-up duration was 1.6 years. Mortality HRs of patients who initiated at 0 to ≤7 days, >14 days to ≤1 month, >1 to ≤2 months, >2 months, and before initiation were 1.59, 1.19, 1.56, 1.08, and 0.94, respectively, compared with the reference group of >7 to ≤14 days. LTFU HRs were 1.02, 1.07, 0.85, 0.97, and 3.96, respectively. Among patients not on ART, 88% of deaths and 85% of LTFU occurred during the first 3 months after becoming ART eligible, but only 37% and 29% among adolescents on ART, respectively., Conclusions: Neither mortality or LTFU was associated with varying time to ART. The initiation process can be tailored to the adolescents' needs and individual life situations without risking to increase poor treatment outcomes. Early mortality was high despite rapid ART initiation, calling for earlier rather than faster initiation through HIV testing scale-up.

Background . In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology . This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results . Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46-282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35-4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10-1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44-2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22-0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion . There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost., Methods: An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted., Findings: In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6% increase in the proportion of ART experienced people with viral load < 1000 cps/mL was cost effective if it cost up to $50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost-effective when costing $23-$32 per year, depending on whether the adherence intervention is used to reduce the level of need for viral load measurement., Conclusion: The cost thresholds identified suggest that there is clear scope for adherence monitoring-based interventions to provide net population health gain, with potential cost-effective use in situations where viral load monitoring is or is not available. Our results guide the implementation of future adherence monitoring interventions found in randomized trials to have health benefit., Competing Interests: The authors have declared that no competing interests exist.

Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability.

Background: Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010., Methods: Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites., Results: A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002)., Conclusions: The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Introduction: Zimbabwe has a high human immunodeficiency virus (HIV) burden. It is therefore important to scale up HIV-testing and counseling (HTC) as a gateway to HIV prevention, treatment and care., Objective: To determine factors associated with being HIV-tested among adult men and women in Zimbabwe., Methods: Secondary analysis was done using data from 7,313 women and 6,584 men who completed interviewer-administered questionnaires and provided blood specimens for HIV testing during the Zimbabwe Demographic and Health Survey (ZDHS) 2010-11. Factors associated with ever being HIV-tested were determined using multivariate logistic regression., Results: HIV-testing was higher among women compared to men (61% versus 39%). HIV-infected respondents were more likely to be tested compared to those who were HIV-negative for both men [adjusted odds ratio (AOR) = 1.53; 95% confidence interval (CI) (1.27-1.84)] and women [AOR = 1.42; 95% CI (1.20-1.69)]. However, only 55% and 74% of these HIV-infected men and women respectively had ever been tested. Among women, visiting antenatal care (ANC) [AOR = 5.48, 95% CI (4.08-7.36)] was the most significant predictor of being tested whilst a novel finding for men was higher odds of testing among those reporting a sexually transmitted infection (STI) in the past 12 months [AOR = 1.86, 95%CI (1.26-2.74)]. Among men, the odds of ever being tested increased with age ≥ 20 years, particularly those 45-49 years [AOR = 4.21; 95% CI (2.74-6.48)] whilst for women testing was highest among those aged 25-29 years [AOR = 2.01; 95% CI (1.63-2.48)]. Other significant factors for both sexes were increasing education level, higher wealth status and currently/formerly being in union., Conclusions: There remains a high proportion of undiagnosed HIV-infected persons and hence there is a need for innovative strategies aimed at increasing HIV-testing, particularly for men and in lower-income and lower-educated populations. Promotion of STI services can be an important gateway for testing more men whilst ANC still remains an important option for HIV-testing among pregnant women.

Objective: This study evaluated the performance of sentinel sites in preventing the emergence of HIVDR using Early Warning Indicators (HIVDR EWI) survey., Methods: Adult and paediatric patient data on: On time pill pick up, Retention in care, Pharmacy stock-outs, and Dispensing practices was collected. Information from pharmacy registers was verified using facility-held cards. This was a cross-sectional analysis of retrospectively collected data from 72 sites providing both adult and paediatric ART as well as two providing adult ART only. All data were entered into and analysed using a WHO EWI data abstraction electronic tool., Results: Twenty-one percent of sites providing adult and 4.2% of sites providing paediatric ART managed to meet the target for on time pill pick up. Retention in care indicator was met by 48.7% (95% CI: 36.9-60.6) of sites. ARV stock-outs occurred in 81.1% (95% CI: 70-89.3) adult sites and 63.9% (95% CI: 50-78.6) paediatric sites. ARVs were appropriately dispensed by 86.5% (95% CI: 75.6-93.3) of adult sites and 84.7% (95% CI: 74.3-92.1) of paediatric sites., Conclusions: Most sites had low performance in many indicators in this survey and failed to meet the recommended targets. Some policies such as the current buffer stock and storage outside Harare should be revised in order to improve site access to ARVs. The country should prioritize the provision of viral load testing services in all provinces. The electronic patient management system should be rolled out to all ART sites to improve patient tracking and monitoring by sites.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Background: Delayed presentation of pulmonary TB (PTB) patients for treatment from onset of symptoms remains a threat to controlling individual disease progression and TB transmission in the community. Currently, there is insufficient information about treatment delays in Zimbabwe, and we therefore determined the extent of patient and health systems delays and their associated factors in patients with microbiologically confirmed PTB., Methods: A structured questionnaire was administered at 47 randomly selected health facilities in Zimbabwe by trained health workers to all patients aged ≥18 years with microbiologically confirmed PTB who were started on TB treatment and entered in the health facility TB registers between 01 January and 31 March 2013. Multivariate logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for associations between patient/health system characteristics and patient delay >30 days or health system delay >4 days., Results: Of the 383 recruited patients, 211(55%) were male with an overall median age of 34 years (IQR, 28-43). There was a median of 28 days (IQR, 21-63) for patient delays and 2 days (IQR, 1-5) for health system delays with 184 (48%) and 118 (31%) TB patients experiencing health system delays >30 days and health system delays >4 days respectively. Starting TB treatment at rural primary healthcare vs district/mission facilities [aOR 2.70, 95% CI 1.27-5.75, p = 0.01] and taking self-medication [aOR 2.33, 95% CI 1.23-4.43, p = 0.01] were associated with encountering patient delays. Associated with health system delays were accessing treatment from lower level facilities [aOR 2.67, 95% CI 1.18-6.07, p = 0.019], having a Gene Xpert TB diagnosis [aOR 0.21, 95% CI 0.07-0.66, p = 0.008] and >4 health facility visits prior to TB diagnosis [(aOR) 3.34, 95% CI 1.11-10.03, p = 0.045]., Conclusion: Patient delays were longer and more prevalent, suggesting the need for strategies aimed at promoting timely seeking of appropriate medical consultation among presumptive TB patients. Health system delays were uncommon, suggesting a fairly efficient response to microbiologically confirmed PTB cases. Identified risk factors should be explored further and specific strategies aimed at addressing these factors should be identified in order to lessen patient and health system delays.

Objectives: To determine (1) gender-related differences in antiretroviral therapy (ART) outcomes, and (2) gender-specific characteristics associated with attrition., Methods: This was a retrospective patient record review of 3919 HIV-infected patients aged ≥15 years who initiated ART between 2007 and 2009 in 40 randomly selected ART facilities countrywide., Results: Compared to females, males had more documented active tuberculosis (12% vs. 9%; p<0.02) and a lower median CD4 cell count (117 cells/μl vs. 143 cells/μl; p<0.001) at ART initiation. Males had a higher risk of attrition (adjusted hazard ratio (AHR) 1.28, 95% confidence interval (CI) 1.10-1.49) and mortality (AHR 1.56, 95% CI 1.10-2.20). Factors associated with attrition for both sexes were lower baseline weight (<45kg and 45-60kg vs. >60kg), initiating ART at an urban health facility, and care at central/provincial or district/mission hospitals vs. primary healthcare facilities., Conclusions: Our findings show that males presented late for ART initiation compared to females. Similar to other studies, males had higher patient attrition and mortality compared to females and this may be attributed in part to late presentation for HIV treatment and care. These observations highlight the need to encourage early HIV testing and enrolment into HIV treatment and care, and eventually patient retention on ART, particularly amongst men., Competing Interests: The authors declare that they fulfil the criteria for authorship and that no author has any financial or non-financial association to an institution that might have an interest in the submitted work. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the organizations and/or agencies to which the authors are affiliated., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Though great progress has been realized over the last decade in extending HIV prevention, care and treatment in some of the least resourced settings of the world, a substantial gap remains between what we know works and what we are actually achieving in HIV programs. To address this, leaders have called for the adoption of an implementation science framework to improve the efficiency and effectiveness of HIV programs. Implementation science (IS) is a multidisciplinary scientific field that seeks generalizable knowledge about the magnitude of, determinants of and strategies to close the gap between evidence and routine practice for health in real-world settings. We propose an IS approach that is iterative in nature and composed of four major components: 1) Identifying Bottlenecks and Gaps, 2) Developing and Implementing Strategies, 3) Measuring Effectiveness and Efficiency, and 4) Utilizing Results. With this framework, IS initiatives draw from a variety of disciplines including qualitative and quantitative methodologies in order to develop new approaches responsive to the complexities of real world program delivery. In order to remain useful for the changing programmatic landscape, IS research should factor in relevant timeframes and engage the multi-sectoral community of stakeholders, including community members, health care teams, program managers, researchers and policy makers, to facilitate the development of programs, practices and polices that lead to a more effective and efficient global AIDS response. The approach presented here is a synthesis of approaches and is a useful model to address IS-related questions for HIV prevention, care and treatment programs. This approach, however, is not a panacea, and we will continue to learn new ways of thinking as we move forward to close the implementation gap.

Background: Pediatric antiretroviral treatment coverage in resource-limited settings continues to lag behind adults. Task shifting is an effective approach broadly used for adults, which some countries have also adopted for children, but implementation is limited by lack of confidence and skills among nonspecialist staff., Methods: A systematic review was conducted by combining key terms for task shifting, antiretroviral therapy (ART), and children. Five databases and two conferences were searched from inception till August 01, 2013., Results: Eight observational studies provided outcome data for 11,828 children who received ART from nonphysician providers across 10 countries in sub-Saharan Africa. The cumulative pooled proportion of deaths was 3.2% [95% confidence interval (CI): 2.0 to 4.5] at 6 months, 4.6% (95% CI: 2.1 to 7.1) at 12 months, 6.2% (95% CI: 3.7 to 8.8) at 24 months, and 5.9% (95% CI: 3.5 to 8.3) at 36 months. Mortality and loss to follow-up in task-shifting programs were comparable to those reported by programs providing doctor- or specialist-led care., Conclusions: Our review suggests that task shifting of ART care can result in outcomes comparable to routine physician care, and this approach should be considered as part of a strategy to scale-up pediatric treatment. Specialist care will remain important for management of sick patients and complicated cases. Further qualitative research is needed to inform optimal implementation of task shifting for pediatric patients.

Background: Since establishment of Zimbabwe's National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored., Objective: To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART., Methods: A retrospective review of abstracted patient records of adults ≥ 15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition., Results: Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1-1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1-2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4-2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1-11.2)., Conclusions: Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention.

Purpose of Review: We reviewed recent literature on the cascade of HIV care from HIV testing to suppression of viral load, which has emerged as a critical focus as HIV treatment programs have scaled up., Recent Findings: In low- and middle-income countries, HIV testing and diagnosis of people living with HIV (PLHIV), although rapidly expanding, are generally relatively low. Linkage and retention in care are global challenges, with substantial attrition between diagnosis, laboratory or clinical staging, and antiretroviral therapy (ART) initiation, and additional substantial attrition on ART due to loss to follow-up and death. ART coverage is rapidly expanding but is still relatively low, especially when considered as a percentage of all PLHIV. Adherence is also suboptimal and virological suppression is incomplete., Summary: Taken together, the attrition at each step of the cascade of care results in overall low levels of viral load suppression in the total population of PLHIV. More robust monitoring from the facility to global levels and implementation of established and emerging interventions are needed at each step of the cascade to enhance HIV diagnosis, linkage to and retention in care, ART use, and adherence, and ultimately reduce viral load, improve clinical outcomes, and reduce HIV transmission.

Background: Zimbabwe is among the 22 Tuberculosis (TB) high burden countries worldwide and runs a well-established, standardized recording and reporting system on case finding and treatment outcomes. During TB treatment, patients transfer-out and transfer-in to different health facilities, but there are few data from any national TB programmes about whether this process happens and if so to what extent. The aim of this study therefore was to describe the characteristics and outcomes of TB patients that transferred into Harare City health department clinics under the national TB programme. Specific objectives were to determine i) the proportion of a cohort of TB patients registered as transfer-in, ii) the characteristics and treatment outcomes of these transfer-in patients and iii) whether their treatment outcomes had been communicated back to their respective referral districts after completion of TB treatment., Methods: Data were abstracted from patient files and district TB registers for all transfer-in TB patients registered from January to December 2010 within Harare City. Descriptive statistics were calculated., Results: Of the 7,742 registered TB patients in 2010, 263 (3.5%) had transferred-in: 148 (56%) were males and overall median age was 33 years (IQR, 26-40). Most transfer-in patients (74%) came during the intensive phase of TB treatment, and 58% were from rural health-facilities. Of 176 patients with complete data on the time period between transfer-in and transfer-out, only 85 (48%) arrived for registration in Harare from referral districts within 1 week of being transferred-out. Transfer-in patients had 69% treatment success, but in 21% treatment outcome status was not evaluated. Overall, 3/212 (1.4%) transfer-in TB patients had their TB treatment outcomes reported back to their referral districts., Conclusion: There is need to devise better strategies of following up TB patients to their referral Directly Observed Treatment (DOT) centres from TB diagnosing centres to ensure that they arrive promptly and on time. Recording and reporting of information must improve and this can be done through training and supervision. Use of mobile phones and other technology to communicate TB treatment outcomes back to the referral districts would seem the obvious way to move forward on these issues.