Uptake of community health care provision by community health entrepreneurs for febrile illness and diarrhoea: a cross-sectional survey in rural communities in Bunyangabu district, Uganda.

OBJECTIVE: To assess the uptake of services provided by community health workers who were trained as community health entrepreneurs (CHEs) for febrile illness and diarrhoea. DESIGN: A cross-sectional survey among households combined with mapping of all providers of basic medicine and primary health services in the study area. PARTICIPANTS: 1265 randomly selected households in 15 rural villages with active CHEs. SETTING: Bunyangabu district, Uganda. OUTCOME MEASURES: We describe the occurrence and care sought for fever and diarrhoea in the last 3 months by age group in the households. Care provider options included: CHE, health centre or clinic (public or private), pharmacy, drug shop and other. Geographic Information Ssystem (GIS)-based geographical measures were used to map all care providers around the active CHEs. RESULTS: Fever and diarrhoea in the last 3 months occurred most frequently in children under 5; 68% and 41.9%, respectively. For those who sought care, CHE services were used for fever among children under 5, children 5-17 and adults over 18 years of age in 34.7%, 29.9% and 25.1%, respectively. For diarrhoea among children under 5, children 5-17 and adults over 18 years of age, CHE services were used in 22.1%, 19.5% and 7.0%, respectively. For those who did not seek care from a CHE (only), drug shops were most frequently used services for both fever and diarrhoea, followed by health centres or private clinics. Many households used a combination of services, which was possible given the high density and diversity of providers found in the study area. CONCLUSIONS: CHEs play a considerable role in providing care in rural areas where they are active. The high density of informal drug shops and private clinics highlights the need for clarity on the de facto roles played by different providers in both the public and private sector to improve primary healthcare.

Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi.

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.

High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.

BACKGROUND: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. CONCLUSIONS: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi.

Background: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. Methods: Data were collected from a prospective cohort of infants HIV-exposed aged 1-6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi's Prevention of Mother-to-Child Transmission of HIV Programme (2014-2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P < 0.1. Results: A total of 1,206 singleton CHEU and their mothers were enrolled and 563 completed the follow-up through 24 months of age. Moreover, 48% of CHEU were exposed to ART from conception, 40% from first/second trimester, and 12% from third trimester/postpartum. At enrollment, 12% of infants had low birthweight (LBW), 98% had been breastfed in past 7 days, and 57% were enrolled in an HIV care clinic. CHEU growth trajectories demonstrated cohort-wide growth faltering after the age of 12 months. Of 788 and 780 CHEU contributing to WAZ and LAZ multivariable models, respectively, there was no evidence of differences in mean WAZ or LAZ among those exposed from conception or first/second trimester vs. third trimester/postpartum and no evidence of a difference in WAZ or LAZ rate of change by timing of ART exposure (all interactions P > 1.0). Conclusion: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life.

The National Evaluation of Malawi's PMTCT Program (NEMAPP) study: 24-month HIV-exposed infant outcomes from a prospective cohort study.

OBJECTIVES: Data on long-term HIV-free survival in breastfeeding, HIV-exposed infants (HEIs) are limited. The National Evaluation of Malawi's Prevention of Mother-to-Child Transmission (PMTCT) Program (NEMAPP), conducted between 2014 and 2018, evaluated mother-to-child transmission (MTCT) and infant outcomes up to 24 months postpartum. METHODS: We enrolled a nationally representative cohort of HEIs at 54 health facilities across four regional strata in Malawi and used multivariable Cox regression analysis to investigate the risk of adverse outcomes (HIV transmission, infant death and loss to follow-up) to 24 months postpartum. Models, controlling for survey design, were fitted for the total cohort (n = 3462) and for a subcohort that received maternal viral load (VL) monitoring (n = 1282). RESULTS: By 24 months, in 3462 HEIs, weighted cumulative MTCT was 4.9% [95% confidence interval (CI) 3.7-6.4%], 1.3% (95% CI 0.8-2.2%) of HEIs had died, 26.2% (95% CI 24.0-28.6%) had been lost to follow-up and 67.5% (95% CI 65.0-70.0%) were alive and HIV-free. Primiparity [weighted adjusted hazard ratio (aHR) 1.6; 95% CI 1.1-2.2; parity 2-3: weighted aHR 1.5; 95% CI 1.2-1.9], the mother not disclosing her HIV status to her partner (no disclosure: weighted aHR 1.3; 95% CI 1.1-1.6; no partner: weighted aHR 0.7; 95% CI 0.5-0.9), unknown maternal ART start (weighted aHR 2.0; 95% CI 1.0-3.9) and poor adherence (missed ≥ 2 days of ART in the last month: weighted aHR 1.7; 95% CI 1.2-2.2; not on ART: weighted aHR 1.7; 95% CI 1.0-2.7) were associated with adverse outcomes by 24 months. In the subcohort analysis, risk of HIV transmission or infant death was higher among HEIs whose mothers started ART post-conception (during pregnancy: weighted aHR 3.2; 95% CI 1.3-7.7; postpartum: weighted aHR 12.4; 95% CI 1.5-99.6) or when maternal viral load at enrolment was > 1000 HIV-1 RNA copies/mL (weighted aHR 15.7; 95% CI 7.8-31.3). CONCLUSIONS: Infant positivity and infant mortality at 24 months were low for a breastfeeding population. Starting ART pre-conception had the greatest impact on HIV-free survival in HEIs. Further population-level reduction in MTCT may require additional intervention during breastfeeding for women new to PMTCT programmes. Pre-partum diagnosis and linkage to ART, followed by continuous engagement in care during breastfeeding can further reduce MTCT but are challenging to implement.

Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.

BACKGROUND: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa. METHODS: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. RESULTS: Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. CONCLUSIONS: Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU.

Process evaluation of an implementation strategy to support uptake of a tuberculosis treatment adherence intervention to improve TB care and outcomes in Malawi.

OBJECTIVE: To assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence. DESIGN: Mixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework. SETTING: Forty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training. PARTICIPANTS: Forty-five peer-trainers (PTs), 23 patients and 20 LHWs. INTERVENTION: Implementation strategy employing peer-led educational outreach, a clinical support tool and peer support network to implement a TB treatment adherence intervention. OUTCOME MEASURES: Process data were collected from study initiation to the end-of-study PT meeting, and included: LHW and patient interviews, quarterly PT meeting notes, training logs and study team observations and meeting notes. Data sources were first analysed in isolation, followed by method, data source and analyst triangulation. Analyses were conducted independently by two study team members, and themes revised through discussion and involvement of additional study team members as needed. RESULTS: Forty-one HCs (91%) trained at least one LHW. Of 256 LHWs eligible to participate at study start 152 (59%) completed training, with the proportion trained per HC ranging from 0% to 100% at the end of initial cascade training. Lack of training incentives was the primary barrier to implementation, with intrinsic motivation to improve knowledge and skills, and to improve patient care and outcomes the primary facilitators of participation. CONCLUSION: We identified important challenges to and potential facilitators of implementation, scalability and sustainability, of the TB treatment adherence intervention. Findings provide guidance to scale-up, and use of the implementation strategies employed, to address LHW training and supervision in other areas. TRIAL REGISTRATION NUMBER: NCT02533089.

Early post-partum viremia predicts long-term non-suppression of viral load in HIV-positive women on ART in Malawi: Implications for the elimination of infant transmission.

BACKGROUND: Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum. METHODS: 1-6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014-2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management. RESULTS: 596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p<0.01), had higher parity (p = 0.03) and more likely to have undetectable VL at enrollment than those lost to follow-up (80.0% vs 70.2%, p<0.01). Of 590 women on ART (median 30.1 months; inter-quartile range 26.8-61.3), 442 (74.9%) with complete VL data at 3 visits were included in further analysis. Prevalence of detectable VL at 12 and 24 months was higher among women with detectable VL at enrollment than among those with undetectable VL (74 detectable VL results/66 women vs. 19/359; p<0.001). In multivariable analysis (adjusted for age, parity, education, partner disclosure, timing of ART start and self-reported adherence), detectable VL at 24 months was 9 times more likely among women with 1 prior detectable VL (aOR 9.0; 95%CI 3.5-23.0, p<0.001) and 226 times more likely for women with 2 prior detectable VLs (aOR 226.4; 95%CI 73.0-701.8, p<0.001). CONCLUSIONS: Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.

Decentralising diabetes care from hospitals to primary health care centres in Malawi.

BACKGROUND: Non-communicable diseases (NCDs) such as diabetes and hypertension have become a prominent public health concern in Malawi, where health care services for NCDs are generally restricted to urban centres and district hospitals, while the vast majority of Malawians live in rural settings. Whether similar quality of diabetes care can be delivered at health centres compared to hospitals is not known. METHODS: We implemented a pilot project of decentralized diabetes care at eight health centres in four districts in Malawi. We described differences between district hospitals and rural health centres in terms of patient characteristics, diabetes complications, cardiovascular risk factors, and aspects of the quality of care and used multivariate logistic regression to explore factors associated with adequate diabetes and blood pressure control. RESULTS: By March 2019, 1339 patients with diabetes were registered of whom 286 (21%) received care at peripheral health centres. The median duration of care of patients in the diabetes clinics during the study period was 8.8 months. Overall, HIV testing coverage was 93.6%, blood pressure was recorded in 92.4%; 68.5% underwent foot examination of whom 35.0% had diabetic complications; 30.1% underwent fundoscopy of whom 15.6% had signs of diabetic retinopathy. No significant differences in coverage of testing for diabetes complications were observed between health facility types. Neither did we find significant differences in retention in care (72.1 vs. 77.6%; p=0.06), adequate diabetes control (35.0% vs. 37.8%; p=0.41) and adequate blood pressure control (51.3% vs. 49.8%; p=0.66) between hospitals and health centres. In multivariate analysis, male sex was associated with adequate diabetes control, while lower age and normal body mass index were associated with adequate blood pressure control; health facility type was not associated with either. CONCLUSION: Quality of care did not appear to differ between hospitals and health centres, but was insufficient at both levels.

Impact of a tuberculosis treatment adherence intervention versus usual care on treatment completion rates: results of a pragmatic cluster randomized controlled trial.

BACKGROUND: With the global shortage of skilled health workers estimated at 7.2 million, outpatient tuberculosis (TB) care is commonly task-shifted to lay health workers (LHWs) in many low- and middle-income countries where the shortages are greatest. While shown to improve access to care and some health outcomes including TB treatment outcomes, lack of training and supervision limit the effectiveness of LHW programs. Our objective was to refine and evaluate an intervention designed to address common causes of non-adherence to TB treatment and LHW knowledge and skills training needs. METHODS: We employed a pragmatic cluster randomized controlled trial. Participants included 103 health centres (HCs) providing TB care in four districts in Malawi, randomized 1:1 stratified by district and HC funding (Ministry of Health, non-Ministry funded). At intervention HCs, a TB treatment adherence intervention was implemented using educational outreach, a point-of-care reminder tool, and a peer support network. Clusters in the control arm provided usual care. The primary outcome was the proportion of patients with successful TB treatment (i.e., cure or treatment completion). We used a generalized linear mixed model, with district as a fixed effect and HC as a random effect, to compare proportions of patients with treatment success, among the trial arms, with adjustment for baseline differences. RESULTS: We randomized 51 HCs to the intervention group and 52 HCs to the control group. Four intervention and six control HCs accrued no eligible patients, and 371 of 1169 patients had missing outcome, HC, or demographic data, which left 74 HCs and 798 patients for analysis. Randomization group was not related to missing outcome, however, district, age, and TB type were significantly related and included in the primary analysis model. Among the 1153 patients with HC and demographic data, 297/605 (49%) and 348/548 (64%) in the intervention and control arms, respectively, had treatment success. The intervention had no significant effect on treatment success (adjusted odds ratio 1.35 [95% confidence interval 0.93-1.98]). CONCLUSION: We found no significant effect of the intervention on TB treatment outcomes with high variability in implementation quality, highlighting important challenges to both scale-up and sustainability. TRIAL REGISTRATION: ClinicalTrials.gov NCT02533089 . Registered August 20, 2015.

Impact of peer-trainer leadership style on uptake of a peer led educational outreach intervention to improve tuberculosis care and outcomes in Malawi: a qualitative study.

BACKGROUND: Little is known about how to build leadership capacity to support implementation of evidence-based practices within health systems. We observed substantial variability across sites in uptake and sustainability of a peer-led educational outreach intervention for lay health workers (LHWs) providing tuberculosis care in Malawi. Feedback from peer-trainers (PTs) suggested that leadership may have contributed to the variation. We sought to assess the impact of PT leadership style on implementation, and to identify leadership traits of more successful PTs, to inform future implementation planning and to identify targets for leadership capacity building. METHODS: Qualitative study employing interviews with PTs and LHWs at high and low implementation sites, and review of study team and quarterly PT meeting notes. High implementation sites achieved high uptake, sustainability and fidelity of implementation including: close adherence to training content and process, high levels of coverage (training most or all eligible LHWs at their site), and outcomes were achieved with high levels of self reported competence with the intervention among both PTs and LHWs. Low implementation sites achieved limited coverage (<= 50% of LHWs trained), and intervention fidelity. RESULTS: Eight PTs and 10 LHWs from eight high and 10 low implementation sites participated in interviews. Leadership traits of more successful PTs included: flexibility in their approach to training, role modeling and provision of supportive supervision to support learning; addressing challenges proactively and as they occurred; collaborative planning; knowledgeable; and availability to support implementation. Traits unique to less successful PTs included: a poor attitude toward their role as PT and a passive-avoidant approach to challenges. CONCLUSION: This study identified leadership traits more common among unit level leaders at sites with higher uptake, sustainability, and fidelity of implementation. These findings provide a starting point for development and evaluation of a leadership capacity building intervention for unit level leaders to support implementation.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.

What interventions are effective in improving uptake and retention of HIV-positive pregnant and breastfeeding women and their infants in prevention of mother to child transmission care programmes in low-income and middle-income countries? A systematic review and meta-analysis.

OBJECTIVE: This review was conducted to identify interventions effective in improving uptake and retention of HIV-positive mothers and their infants in prevention of mother to child transmission (PMTCT) services in low-income and middle-income countries (LMICs) in order to inform programme planning. METHODS: We conducted a systematic review of studies comparing usual care with any intervention to improve uptake and retention of HIV-positive pregnant or breastfeeding women and their children from birth to 2 years of age in PMTCT services in LMICs. Twenty-two electronic databases were searched from inception to 15 January 2018, for randomised, quasi-randomised and non-randomised controlled trials, and interrupted time series studies; reference lists of included articles were searched for relevant articles. Risk of bias was assessed using the Cochrane Effective Practice and Organisation of Care group criteria. Random-effects meta-analysis was conducted for studies reporting similar interventions and outcomes. RESULTS: We identified 29 837 articles, of which 18 studies were included in our review. Because of heterogeneity in interventions and outcome measures, only one meta-analysis of two studies and one outcome was conducted; we found a statistically significant increase in antiretroviral therapy (ART) use during pregnancy for integration of HIV and antenatal care relative to standard non-integrated care (pooled AOR=2.69; 95% CI 1.25 to 5.78, p=0.0113). The remaining studies assessing other patient, provider or health system interventions were synthesised narratively, with small effects seen across intervention categories for both maternal and infant PMTCT outcomes based predominately on evidence with moderate to high risk of bias. CONCLUSIONS: Evidence on the effectiveness of interventions to improve uptake and retention of mothers and infants in PMTCT care is lacking. Our findings suggest that integration of HIV and antenatal care may improve ART use during pregnancy. Future studies to replicate promising approaches are needed. Improved reporting of key methodological criteria will facilitate interpretation of findings and improve the utility of evidence to PMTCT programme planners. PROSPERO REGISTRATION NUMBER: CRD42015020829.

Impact of inter-partner HIV disclosure patterns in Malawi's PMTCT program: A mixed-method study.

BACKGROUND: Evidence suggests that disclosure of HIV status between partners may influence prevention of maternal-to-child transmission of HIV (PMTCT) outcomes. We report partner disclosure in relation to maternal antiretroviral therapy (ART) uptake and adherence, and MTCT among postpartum HIV-infected Malawian women. METHODS: A cross-sectional mixed-method study was conducted as part of a nationally representative longitudinal cohort study. Between 2014-2016, all (34,637) mothers attending 54 under-5 clinics with their 4-26 week-old infants were approached, of which 98% (33,980) were screened for HIV; infants received HIV-1 DNA testing. HIV-exposure was confirmed in 3,566/33,980 (10.5%). Baseline data from mothers who were known to be HIV-infected at time of screening were included in the current analysis. Guardians (n = 17), newly diagnosed HIV-infected mothers (n = 256) and mothers or infants with undetermined HIV status (n = 30) were excluded. Data collected included socio-demographics, partner disclosure, maternal ART uptake, and adherence. Between 2016-2017, in-depth interviews and focus group discussions were conducted with adult mothers (n = 53) and their spouse/cohabiting partners (n = 19), adolescent mothers (n = 13), lost-to-follow up (LTFU) mothers (n = 22), community leaders (n = 23) and healthcare workers (n = 154). RESULTS: Of 3153 known HIV-infected mothers, 2882 (91.4%) reported having a spouse/cohabiting partner. Among 2882 couples, both partners, one partner, and neither partner disclosed to each other in 2090 (72.5%), 622 (21.6%), and 169 (5.9%), respectively. In multivariable models, neither partner disclosing was associated with no maternal ART (aOR 4.7; 95%CI 2.5-8.8), suboptimal treatment adherence (aOR 1.8; 95%CI 1.1-2.8) and MTCT (aOR 2.1; 95%CI 1.1-4.1). Women's fear of blame by partners was central to decisions not to disclose within couples and when starting new relationships. LTFU mothers struggled to accept and disclose their status, hindering treatment initiation; some were unable to hide ART and feared involuntary disclosure. CONCLUSION: Partner disclosure seems to play an important role in women's decisions regarding ART initiation and adherence. Inter-partner non-disclosure was associated with no ART uptake, suboptimal treatment adherence and MTCT.

Extending Visit Intervals for Clinically Stable Patients on Antiretroviral Therapy: Multicohort Analysis of HIV Programs in Southern Africa.

BACKGROUND: The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS: We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load <1000 copies/mL), immunological (CD4 >200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS: We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION: Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.

Low detectable postpartum viral load is associated with HIV transmission in Malawi's prevention of mother-to-child transmission programme.

INTRODUCTION: In 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. METHODS: HIV-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. RESULTS: Of 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). CONCLUSIONS: Unsuppressed 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.

Changes in rapid HIV treatment initiation after national "treat all" policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis.

BACKGROUND: Most countries have formally adopted the World Health Organization's 2015 recommendation of universal HIV treatment ("treat all"). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. METHODS AND FINDINGS: We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI -2.9 to 3.8; p = 0.804) and Uganda (-4.2 pp, 95% CI -9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16-24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. CONCLUSIONS: Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.

Correction: Pregnancy intention and contraceptive use among HIV-positive Malawian women at 4-26 weeks post-partum: A nested cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0215947.].

Pregnancy intention and contraceptive use among HIV-positive Malawian women at 4-26 weeks post-partum: A nested cross-sectional study.

BACKGROUND: Avoiding unintended pregnancies through family planning is a WHO strategy for preventing mother to child transmission of HIV (PMTCT) and maternal morbidity/mortality. We investigated factors associated with unintended index pregnancy, unmet contraceptive need, future pregnancy intention and current contraceptive use among Malawian women living with HIV in the Option B+ era. METHODS: Women who tested HIV positive at 4-26 weeks postpartum were enrolled into a cross-sectional study at high-volume Under-5 clinics. Structured baseline interviews included questions on socio-demographics, HIV knowledge, partner's HIV status/disclosure, ART use, pregnancy intention and contraceptive use. Logistic regression was used to determine factors associated with outcomes. RESULTS: We enrolled 578 HIV-positive women between May 2015-May 2016; median maternal age was 28 years (y) (interquartile-range [IQR]: 23-32), median parity was 3 deliveries (IQR: 2-4) and median infant age was 7 weeks (IQR: 6-12). Overall, 41.8% women reported unintended index pregnancy, of whom 35.0% reported unmet contraceptive need and 65.0% contraceptive failure. In multivariable analysis, unintended index pregnancy was higher in ≥35y vs. 14-24y (adjusted Odds Ratio [aOR]: 2.1, 95% Confidence Interval [95%CI]: 1.0-4.2) and in women with parity ≥3 vs. primiparous (aOR: 2.9, 95%CI: 1.5-5.6). Unmet contraceptive need at conception was higher in 14-24y vs. ≥35y (aOR: 4.2, 95%CI: 1.8-9.9), primiparous vs. ≥3 (aOR: 8.3, 95%CI: 1.8-39.5), and women with a partner of unknown HIV-status (aOR: 2.2, 95%CI: 1.2-4.0). Current contraceptive use was associated with being on ART in previous pregnancy (aOR: 2.5, 95%CI: 1.5-3.9). CONCLUSIONS: High prevalence of unintended index pregnancy and unmet contraceptive need among HIV-positive women highlight the need for improved access to contraceptives. To help achieve reproductive goals and elimination of MTCT of HIV, integration of family planning into HIV care should be strengthened to ensure women have timely access to a wide range of family planning methods with low failure risk.

Retention on antiretroviral therapy during Universal Test and Treat implementation in Zomba district, Malawi: a retrospective cohort study.

INTRODUCTION: Since 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. METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: Retention 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.