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AbstractIntroduction: Antiretroviral therapy (ART) outcomes that include viral suppression rates are rarely reported among African prison populations. Prisoners deal with specific challenges concerning adherence to ART. We aimed to describe virological outcomes of ART in a large prison in Malawi.Methods: A cross‐sectional study of ART outcomes was conducted at the Zomba Central Prison HIV clinic, Malawi, following the introduction of routine viral load monitoring. All prisoners on ART for at least 6 months were eligible for a viral load test. Patients with ≥1,000 copies/ml received adherence support for 3 months, after which a second VL sample was taken. Patients with ≥5,000 copies/ml on the second sample had virological failure and started 2nd line ART. We describe demographics and patient characteristics and report prevalence of potential‐ and documented virological failure. In the potential virological failure rate, those who could not be sampled after 3 months adherence support are included as virological failures. Logistic regression analysis was used to determine factors associated with potential ART failure.Results and discussion: Viral load testing was started at the end of 2014, when 1054 patients had ever registered on ART. Of those, 501 (47.5%) had transferred out to another clinic, 96 (9.1%) had died, 11 defaulted (1.0%) and 3 (0.3%) stopped ART. Of 443 (42.0%) remaining alive in care, an estimated 322 prisoners were on ART >6 months, of whom 262 (81.4%) were sampled. Their median age was 35 years (IQR 31–40) and 257 (98.1%) were male. Self‐reported adherence was good in 258 (98.5%). The rate of potential ART failure was 8.0%, documented ART failure was 4.6% and documented HIV suppression 95.0%. No patient characteristics were independently associated with potential ART failure, possibly due to low numbers with this outcome.Conclusions: Good virological suppression rates can be achieved among Malawian prisoners on ART, under challenging circumstances.

IntroductionData from the Option B+ prevention of mother‐to‐child transmission (PMTCT) program in Malawi show considerable variation between health facilities in retention on antiretroviral therapy (ART). In a programmatic setting, we studied whether the "model of care," based on the degree of integration of antenatal care (ANC), HIV testing and counselling (HTC) and ART service provision–influenced uptake of and retention on ART.MethodsWe conducted a retrospective cohort study of pregnant women seeking ANC at rural primary health facilities in Zomba District, Malawi. Data were extracted from standardized national ANC registers, ART registers and ART master cards. The "model of care" of Option B+ service delivery was determined at each health facility, based on the degree of integration of ANC, HTC and ART. Full integration (Model 1) of HTC and ART initiation at ANC was compared with integration of HTC only into ANC services (Model 2) with subsequent referral to an existing ART clinic for treatment initiation.Results and discussionA total of 10,528 women were newly registered at ANC between October 2011 and March 2012 in 23 rural health facilities (12 were Model 1 and 11 Model 2). HIV status was ascertained in 8,572 (81%) women. Among 914/8,572 (9%) HIV‐positive women enrolling at ANC, 101/914 (11%) were already on ART; of those not on treatment, 456/813 (56%) were started on ART. There was significantly higher ART uptake in Model 1 compared with Model 2 sites (63% vs. 51%; p=0.001), but significantly lower ART retention in Model 1 compared with Model 2 sites (79% vs. 87%; p=0.02). Multivariable analysis showed that initiation of ART on the same day as HIV diagnosis, but not model of care, was independently associated with reduced retention in the first six months (adjusted odds ratio 2.27; 95% CI: 1.34–3.85; p=0.002).ConclusionsHIV diagnosis and treatment on the same day was associated with reduced retention on ART, independent of the level of PMTCT service integration at ANC.

AbstractIntroductionIn 2011, Malawi implemented "Option B+," a test‐and‐treat strategy for the prevention of maternal to child transmission of HIV (PMTCT); however limited data on viral load (VL) suppression exist. We describe VL suppression in HIV‐infected women at four to twenty‐six weeks postpartum, factors associated with VL suppression and the impact of VL suppression levels on MTCT.MethodsHIV‐positive mothers at four to twenty‐six weeks postpartum were enrolled in a nested cross‐sectional study within the "National Evaluation of Malawi's PMTCT Programme" cohort study between October 2014 and May 2016. HIV‐exposed infants received HIV‐1 DNA testing and venous samples determined maternal VL, classified as unsuppressed (>1000 copies/mL), low‐detectable (40 to 1000 copies/mL) or undetectable (<40 copies/mL). Socio‐demographic and PMTCT indicators were collected. Suboptimal adherence was defined as self‐reported ≥2 days missed ART in the month prior to visit.ResultsOf the 1274 women, 1191 (93.5%) knew their HIV status and 1154/1191 (96.9%) were on ART. VL was available for 1124/1154 (97.4%) of women on ART: 988/1124 (87.9%) had VL suppression of whom 86 (8.7%) had low‐detectable and 902 (91.3%) undetectable VL. Suboptimal adherence was associated with unsuppressed VL (vs. suppressed VL; aOR 3.1, 95% CI 2.0 to 4.9; p < 0.001). Women with low‐detectable VL were more likely to be adolescent (vs. undetectable VL; aOR 3.0, 95% CI 1.4 to 6.6), on ART <6 months (aOR 4.4, 95% CI 2.3 to 8.6), report suboptimal adherence (aOR 2.1, 95% CI 1.1 to 3.8; p = 0.02), and less likely to have primary or secondary education (vs. none; aOR 0.3, 95% CI 0.2 to 0.7 or aOR 0.3, 95% 0.1 to 0.6). MTCT ratios among women on ART who had undetectable VL, low‐detectable VL and unsuppressed VL were 0.9% (8/902; 95% CI 0.3 to 1.5), 7.0% (6/86; 95% CI 1.5 to 12.5) and 14.0% (19/136; 95% CI 8.1 to 20.0). Unsuppressed VL and low‐detectable VL (vs. undetectable VL) increased the risk of MTCT 17‐fold (aOR 17.4, 95% CI 7.4 to 41.1; p = 0.002) and ninefold (aOR 8.5, 95% CI 2.9 to 25.2; p < 0.001).ConclusionsUnsuppressed and low‐detectable VL was strongly predictive of MTCT among women on ART and associated with suboptimal adherence. This urges further consideration of optimal VL monitoring and target levels to reach elimination of paediatric infection.

AbstractIntroductionSince June 2016, the national HIV programme in Malawi has adopted Universal Test and Treat (UTT) guidelines requiring that all persons who test HIV positive will be referred to start antiretroviral therapy (ART). Although there is strong evidence from clinical trials that early initiation of ART leads to reduced morbidity and mortality, the impact of UTT on retention on ART in real‐life programmatic settings in Africa is not yet known.MethodsWe conducted a retrospective cohort study in Zomba district, Malawi to compare ART outcomes of patients who initiated ART under 2016 UTT guidelines and those who started ART prior to rollout of UTT (pre‐UTT). We analysed data from 32 rural and urban health facilities of various sizes. Cox proportional hazards modelling was used to determine the independent risk factors of attrition from ART at 12 months. All analyses were adjusted for clustering by health facility using a robust standard errors approach.ResultsAmong 1492 patients (mean age 34.4 years, 933 (63%) female) who initiated ART during the study period, 501 were enrolled in the pre‐UTT cohort and 911 during UTT. At 12 months, retention on ART in the UTT cohort was higher than in the pre‐UTT cohort 83.0% (95% confidence interval (CI): 81.0% to 85.0%) versus 76.2% (95% CI 73.9% to 78.5%). Adolescents, aged 10 to 19 years (adjusted hazard ratio (aHR) 1.53; 95% CI 1.01 to 2.32), and women who were pregnant or breastfeeding at ART initiation (aHR 1.87; 95% CI 1.30 to 2.38) were at higher risk of attrition in the combined pre‐UTT and UTT cohort.ConclusionsRetention on ART was nearly 6% higher after UTT introduction. Young adults and women who were pregnant or breastfeeding at the start of ART were at increased risk of attrition, emphasizing the need for targeted interventions for these groups to achieve the 90‐90‐90 UNAIDS targets in the UTT era.

INTRODUCTION In Sub-Saharan Africa, the rising rates of cerebrovascular and cardiovascular diseases (CBD/CVD) are intersecting with an ageing HIV-infected population. The widespread use of antiretroviral therapy (ART) may confer an additive risk and may not completely suppress the risk associated with HIV infection. High-quality prospective studies are needed to determine if HIV-infected patients in Africa are at increased risk of CBD/CVD and to identify factors associated with this risk. This study will test the hypothesis that immune activation and dysfunction, driven by HIV and reactivation of latent herpesvirus infections, lead to increased CBD/CVD risk in Malawian adults aged ≥35 years. METHODS AND ANALYSIS We will conduct a single-centre, 36-month, prospective cohort study in 800 HIV-infected patients initiating ART and 190 HIV-uninfected controls in Blantyre, Malawi. Patients and controls will be recruited from government ART clinics and the community, respectively, and will be frequency-matched by 5-year age band and sex. At baseline and follow-up visits, we will measure carotid intima-media thickness and pulse wave velocity as surrogate markers of vasculopathy, and will be used to estimate CBD/CVD risk. Our primary exposures of interest are cytomegalovirus and varicella zoster reactivation, changes in HIV plasma viral load, and markers of systemic inflammation and endothelial function. Multivariable regression models will be developed to assess the study's primary hypothesis. The occurrence of clinical CBD/CVD will be assessed as secondary study endpoints. ETHICS AND DISSEMINATION The University of Malawi College of Medicine and Liverpool School of Tropical Medicine research ethics committees approved this work. Our goal is to understand the pathogenesis of CBD/CVD among HIV cohorts on ART, in Sub-Saharan Africa, and provide data to inform future interventional clinical trials. This study runs between May 2017 and August 2020. Results of the main trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER ISRCTN42862937.

The acceleration of prevention of mother-to-child transmission (PMTCT) activities, coupled with the rollout of 2010 World Health Organization (WHO) guidelines, led to important discussions and innovations at global and country levels. One paradigm-shifting innovation was Option B+ in Malawi. It was later included in WHO guidelines and eventually adopted by all 22 Global Plan priority countries. This article presents Malawi's experience with designing and implementing Option B+ and provides complementary narratives from Cameroon and Tanzania. Malawi's HIV program started in 2002, but by 2009, the PMTCT program was lagging far behind the antiretroviral therapy (ART) program because of numerous health system challenges. When WHO recommended Option A and Option B for PMTCT in 2010, it was clear that Malawi's HIV program would not be able to successfully implement either option without increasing existing barriers to PMTCT services and potentially decreasing women's access to care. Subsequent stake-holder discussions led to the development of Option B+. Operationalizing Option B+ required several critical considerations, including the complete integration of ART and PMTCT programs, systematic reduction of barriers to facilitate doubling the number of ART sites in less than a year, building consensus with stakeholders, and securing additional resources for the new program. During the planning and implementation process, several lessons were learned which are considerations for countries transitioning to "treat-all": Comprehensive change requires effective government leadership and coordination; national clinical guidelines must accommodate health system limitations; ART services and commodities should be decentralized within facilities; the general public should be well informed about major changes in the national HIV program; and patients should be educated on clinic processes to improve program monitoring.

AbstractIntroduction: In Malawi, HIV‐infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV‐exposed children are enrolled in the national prevention of mother‐to‐child transmission (PMTCT) programme, but many are lost to follow‐up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow‐up into account.Methods: We abstracted data from HIV‐exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow‐up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk.Results: A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow‐up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV‐negative and 2.2% (1.5–2.8) continued follow‐up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV‐infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed.Conclusions: Confirmed mother‐to‐child transmission rates were low, but due to poor retention only about half of HIV‐infected children were diagnosed. Tracing of children lost to follow‐up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV‐positive children have access to early ART.

IntroductionMalawi introduced a new strategy to improve the effectiveness of prevention of mother‐to‐child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the "model of care") and (ii) explore associations between the "model of care" and health facility–level uptake and retention rates for pregnant women identified as HIV‐positive at antenatal (ANC) clinics.MethodsA health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi's 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports.ResultsAmong 141 health facilities, four "models of care" were identified: A) facilities where newly identified HIV‐positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV‐positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow‐up; C) facilities where newly identified HIV‐positive women are referred from ANC to the ART clinic for initiation and follow‐up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the "model of care" applied; factors independently associated with ART retention were district location, patient volume and the "model of care" applied.ConclusionsA large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the "model of care" chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient‐level research is needed to guide policy recommendations.

AbstractIntroductionAs 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.MethodsWe 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).ResultsThere 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.ConclusionsFor 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.

Africa is experiencing an increasing prevalence of noncommunicable diseases (NCD). However, few reliable data are available on their true burden, main risk factors, and economic impact that are needed to inform implementation of evidence-based interventions in the local context. In Malawi, a number of initiatives have begun addressing the NCD challenge, which have often utilized existing infectious disease infrastructure. It will be crucial to carefully leverage these synergies to maximize their impact. NCD-BRITE (Building Research Capacity, Implementation, and Translation Expertise) is a transdisciplinary consortium that brings together key research institutions, the Ministry of Health, and other stakeholders to build longterm, sustainable, NCD-focused implementation research capacity. Led by University of Malawi—College of Medicine, University of North Carolina, and Dignitas International, NCD-BRITE's specific aims are to conduct detailed assessments of the burden and risk factors of common NCD; assess the research infrastructure needed to inform, implement, and evaluate NCD interventions; create a national implementation research agenda for priority NCD; and develop NCD-focused implementation research capacity through short courses, mentored research awards, and an internship placement program. The capacity-building activities are purposely designed around the University of Malawi—College of Medicine and Ministry of Health to ensure sustainability. The NCD BRITE Consortium was launched in February 2018. In year 1, we have developed NCD-focused implementation research capacity. Needs assessments will follow in years 2 and 3. Finally, in year 4, the generated research capacity, together with findings from the needs assessments, will be used to create a national, actionable, implementation research agenda for NCD prioritized in this consortium, namely cardiovascular disease, diabetes mellitus, and asthma and chronic obstructive pulmonary disease.HighlightsNCD-BRITE is a transdisciplinary consortium that brings together key research institutions, the MOH, and other stakeholders to build long-term, sustainable, NCD-focused implementation research capacity.NCD-BRITE's specific aims are to conduct detailed assessments of the burden and risk factors of common NCD (hypertension, diabetes mellitus, COPD and asthma); assess the research infrastructure needed to inform, implement, and evaluate NCD interventions; create a national implementation research agenda for priority NCD; and develop NCD-focused implementation research capacity through short courses, mentored research awards, and an internship placement program.The capacity-building activities are purposely designed around the College of Medicine and the Government of Malawi MOH to ensure sustainability.It was initiated in 2017 and has successfully completed 2 years of operation.