Community-facility linkage models and maternal and infant health outcomes in Malawi's PMTCT/ART program: A cohort study.

BACKGROUND: In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. METHODS AND FINDINGS: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant "poor outcome" (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ("sites") in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. CONCLUSIONS: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.

Survival and HIV-Free Survival Among Children Aged ≤3 Years - Eight Sub-Saharan African Countries, 2015-2017.

Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)§ survey data, pooled from eight sub-Saharan African countries¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Baseline characteristics of study sites and women enrolled in a three-arm cluster randomized controlled trial: PMTCT uptake and retention (pure) Malawi.

BACKGROUND: Malawi introduced an ambitious public health program known as "Option B+" which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care. METHODS/DESIGN: PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial. RESULTS: Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17-51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75-100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22-31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24-32 months). CONCLUSION: The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov - ID Number NCT02005835 . Registered 4 December, 2013.

The value of informal care in the context of option B+ in Malawi: a contingent valuation approach.

BACKGROUND: Informal care, the health care provided by the patient's social network is important in low income settings although its monetary value is rarely estimated. The lack of estimates of the value of informal care has led to its omission in economic evaluations but this can result in incorrect decisions about cost effectiveness of an intervention. We explore the use of contingent valuation methods of willingness to pay (WTP) and willingness to accept (WTA) to estimate the value of informal care provided to HIV infected women that are accessing antiretroviral therapy (ART) under the Option B+ approach to prevention of mother-to-child transmission (PMTCT) of HIV in Malawi. METHODS: We collected cross sectional data from 93 caregivers of women that received ART care from six health facilities in Malawi. Caregivers of women that reported for ART care on the survey day and consented to participate in the survey were included until the targeted sample size for the facility was reached. We estimated the value of informal care by using the willingness to accept (WTA) and willingness to pay (WTP) approaches. Medians were used to summarize the values and these were compared by the Wilcoxon signed-rank test. RESULTS: The median WTA to provide informal care in a month was US$30 and the median WTP for informal care was US$13 and the two were statistically different (p < 0.000). Median WTP was higher in the urban areas than in the rural areas (US$21 vs. US$13, p < 0.001) and for caregivers from households from higher wealth quintile than in the lower quintile (US$15 vs. US$13, p < 0.0462). CONCLUSION: Informal caregivers place substantial value on informal care giving. In low income settings where most caregivers are not formally employed, WTP and WTA approaches can be used to value informal care. CLINICAL TRIAL NUMBER: NCT02005835.

Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.

BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

"I would love if there was a young woman to encourage us, to ease our anxiety which we would have if we were alone": Adapting the Mothers2Mothers Mentor Mother Model for adolescent mothers living with HIV in Malawi.

BACKGROUND: Pregnant and post-partum adolescent girls and young women (AGYW) living with HIV in sub-Saharan Africa experience inferior outcomes along the prevention of mother-to-child transmission of HIV (PMTCT) cascade compared to their adult counterparts. Yet, despite this inequality in outcomes, scarce data from the region describe AGYW perspectives to inform adolescent-sensitive PMTCT programming. In this paper, we report findings from formative implementation research examining barriers to, and facilitators of, PMTCT care for HIV-infected AGYW in Malawi, and explore strategies for adapting the mothers2mothers (m2m) Mentor Mother Model to better meet AGYW service delivery-related needs and preferences. METHODS: Qualitative researchers conducted 16 focus group discussions (FGDs) in 4 Malawi districts with HIV-infected adolescent mothers ages 15-19 years categorized into two groups: 1) those who had experience with m2m programming (8 FGDs, n = 38); and 2) those who did not (8 FGDs, n = 34). FGD data were analyzed using thematic analysis to assess major and minor themes and to compare findings between groups. RESULTS: Median participant age was 17 years (interquartile range: 2 years). Poverty, stigma, food insecurity, lack of transport, and absence of psychosocial support were crosscutting barriers to PMTCT engagement. While most participants highlighted resilience and self-efficacy as motivating factors to remain in care to protect their own health and that of their children, they also indicated a desire for tailored, age-appropriate services. FGD participants indicated preference for support services delivered by adolescent HIV-infected mentor mothers who have successfully navigated the PMTCT cascade themselves. CONCLUSIONS: HIV-infected adolescent mothers expressed a preference for peer-led, non-judgmental PMTCT support services that bridge communities and facilities to pragmatically address barriers of stigma, poverty, health system complexity, and food insecurity. Future research should evaluate implementation and health outcomes for adolescent mentor mother services featuring these and other client-centered attributes, such as provision of livelihood assistance and peer-led psychosocial support.

Patient and health worker experiences of differentiated models of care for stable HIV patients in Malawi: A qualitative study.

INTRODUCTION: Several models of differentiated care for stable HIV patients on antiretroviral therapy (ART) in Malawi have been introduced to ensure that care is efficient and patient-centered. Three models have been prioritized by the government for a deeper and broader understanding: adjusted appointment spacing through multi-month scripting (MMS); fast-track drug refills (FTRs) on alternating visits; and community ART groups (CAGs) where rotating group members collect medications at the facility for all members. This qualitative study aimed to understand the challenges and successes of implementing these models of care and of the process of patient differentiation. METHODS: A qualitative study was conducted as a part of a broader process evaluation in 30 purposefully selected ART facilities between February and May 2016. Semi-structured, in-depth interviews with 32 health workers that managed and coordinated ART clinics and 30 focus groups were held with 216 ART patients. Interviews and focus groups were audio recorded, transcribed, and coded thematically. RESULTS: Participants reported that the models of differentiated care have yielded key benefits, including: reduced patients' travel and visit time, decongestion of facilities, and enhanced social support. Participants suggested that these benefits could lead to improved HIV treatment outcomes for patients. At the same time, some challenges were reported, such as inconsistent stocks of drugs, which can inhibit implementation of MMS. For CAGs, the group-based nature of the model presented some unique problems, such as conflicts within groups or concerns about privacy. Health workers also described some of the reasons why eligible patients may not receive the models or conversely why ineligible patients sometimes get the models. CONCLUSIONS: Documenting patient and health worker perspectives on models of differentiated care is critical to understanding and improving these models. While these models can offer important benefits, the models may not be appropriate for all sites or patients, and patient status and needs may change over time. Key challenges should be recognized and addressed for optimal utilization of the models.

Multi-month prescriptions, fast-track refills, and community ART groups: results from a process evaluation in Malawi on using differentiated models of care to achieve national HIV treatment goals.

INTRODUCTION: In order to facilitate scale-up of antiretroviral therapy (ART) in Malawi, innovative and pragmatic models have been developed to optimize the efficiency of HIV service delivery. In particular, three models of differentiated care have emerged for stable patients: adjusted appointment spacing through multi-month scripting (MMS); fast-track drug refills (FTRs) on alternating visits; and community ART groups (CAGs) where group members rotate in collecting medications at the facility for all members. This study aimed to assess the extent to which ART patients in Malawi are differentiated based on clinical stability and describe the characteristics and costs associated with the models of differentiated care offered. METHODS: A mixed methods process evaluation was conducted from 30 purposefully selected ART facilities. Cross-sectional data for this evaluation was collected between February and May 2016. The following forms of data collection are reported here: structured surveys with 136 health care workers; reviews of 75,364 patient clinical records; 714 observations of visit time and flow; and 30 questionnaires on facility characteristics. RESULTS: Among ART patients, 77.5% (95% confidence interval [CI] 74.1-80.6) were eligible for differentiated models of care based on criteria for clinical stability from national guidelines. Across all facilities, 69% of patients were receiving MMS. In facilities offering FTRs and CAGs, 67% and 6% of patients were enrolled in the models, respectively. However, eligibility criteria were used inconsistently: 72.9% (95% CI 66.3-78.6) of eligible patients and 42.3% (95% CI 33.1-52.0) ineligible patients received MMS. Results indicated that patient travel and time costs were reduced by 67%, and the unit costs of ART service delivery through the MMS, FTR and CAG models were similar, representing a reduction of approximately 10% in the annual unit cost of providing care to stable patients that receive no model. CONCLUSIONS: MMS is being implemented nationally and has already generated cost savings and efficiencies in Malawi for patients and the health system, but could be improved by more accurate patient differentiation. While expanding FTRs and CAGs may not offer significant further cost savings in Malawi, future studies should investigate if such alternative models lead to improvements in patient satisfaction or clinical outcomes that might justify their implementation.

Building Health System Capacity Through Implementation Research: Experience of INSPIRE-A Multi-country PMTCT Implementation Research Project.

BACKGROUND: The INSPIRE-Integrating and Scaling Up PMTCT through Implementation REsearch-initiative was established as a model partnership of national prevention of mother-to-child transmission of HIV (PMTCT) implementation research in 3 high HIV burden countries-Malawi, Nigeria, and Zimbabwe. INSPIRE aimed to link local research groups with Ministries of Health (MOH), build local research capacity, and demonstrate that implementation research may contribute to improving health care delivery and respond to program challenges. METHODOLOGY: We used a mixed methods approach to review capacity building activities, as experienced by health care workers, researchers, and trainers conducted in the 6 INSPIRE projects before and during study implementation. RESULTS: Between 2011 and 2016, over 3400 health care workers, research team members, and community members participated in INSPIRE activities. This included research prioritization exercises, proposal development, good clinical practice and research ethics training, data management and analysis workshops, and manuscript development. Health care workers in clinics and district health offices acknowledged the value of hosting implementation research projects and how the quality of services improved. Research teams acknowledged the opportunities that projects provided for personal development and the value of participating in a multicountry research network. DISCUSSION: INSPIRE provided an opportunity for African-led research in which researchers worked closely with national MOH to identify priority research questions and implement studies. Close partnerships between research teams and local implementers facilitated project responsiveness to local program issues. Consequently, processes and training needed for study implementation also improved local program management and service delivery. Additional benefits included improved data management, publications, and career development.

Exploring the Experiences of Women and Health Care Workers in the Context of PMTCT Option B Plus in Malawi.

INTRODUCTION: Malawi has embarked on a "test-and-treat" approach to prevent mother-to-child transmission (PMTCT) of HIV, known as "Option B+," offering all HIV-infected pregnant and breastfeeding women lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage. A cross-sectional qualitative study was conducted to explore early experiences surrounding "Option B+" for patients and health care workers (HCWs) in Malawi. METHODS: Study participants were purposively selected across 6 health facilities in 3 regional health zones in Malawi. Semi-structured interviews were conducted with women enrolled in "Option B+" (n = 24), and focus group discussions were conducted with HCWs providing Option B+ services (n = 6 groups of 8 HCWs). Data were analyzed using a qualitative thematic coding framework. RESULTS: Patients and HCWs identified the lack of male involvement as a barrier to retention in care and expressed concerns at the rapidity of the test-and-treat process, which makes it difficult for patients to "digest" a positive diagnosis before starting ART. Fear regarding the breach of privacy and confidentiality were also identified as contributing to loss to follow-up of women initiated under the Option B+. Disclosure remains a difficult process within families and couples. Lifelong ART was also perceived as an opportunity to plan future pregnancies. CONCLUSIONS: As "Option B+" continues to be rolled out, novel interventions to support and retain women into care must be implemented. These include providing space, time, and support to accept a diagnosis before starting ART, engaging partners and families, and addressing the need for peer support and confidentiality.

Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).

BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a prevention of mother-to-child transmission approach providing HIV-infected pregnant and lactating women with immediate lifelong antiretroviral therapy. High maternal attrition has been observed in Option B+. Peer-based support may improve retention. METHODS: A 3-arm stratified cluster randomized controlled trial was conducted in Malawi to assess whether facility- and community-based peer support would improve Option B+ uptake and retention compared with standard of care (SOC). In SOC, no enhancements were made (control). In facility-based and community-based models, peers provided patient education, support groups, and patient tracing. Uptake was defined as attending a second scheduled follow-up visit. Retention was defined as being alive and in-care at 2 years without defaulting. Attrition was defined as death, default, or stopping antiretroviral therapy. Generalized estimating equations were used to estimate risk differences (RDs) in uptake. Cox proportional hazards regression with shared frailties was used to estimate hazard of attrition. RESULTS: Twenty-one facilities were randomized and enrolled 1269 women: 447, 428, and 394 in facilities that implemented SOC, facility-based, and community-based peer support models, respectively. Mean age was 27 years. Uptake was higher in facility-based (86%; RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%, CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD: 16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and community-based peer support interventions can benefit maternal uptake and retention in Option B+.

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

BACKGROUND: In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a cluster-randomized controlled trial evaluating 3 strategies for promoting uptake and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and 699/833 (84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside reverse transcriptase inhibitor class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed confirmed resistance rates suggest that adherence support should be the primary approach for early failure in option B+.

Mother-infant pair clinic and SMS messaging as innovative strategies for improving access to and retention in eMTCT care and Option B+ in Malawi: a cluster randomized control trial (the PRIME study).

UNAIDS has set a goal of achieving the elimination of mother-to-child transmission (eMTCT) of HIV by 2015 and keeping HIV-positive (HIV+) mothers alive. In pursuit of this goal, in 2011, the Malawi Ministry of Health (MoH) adopted the Option B+ strategy, which entails lifelong antiretroviral treatment for all HIV+ mothers, irrespective of severity of HIV infection. Poor mother-child pair retention is one of the major challenges against achieving this goal. To improve retention of mother-infant pairs in the eMTCT continuum of care, the Promoting Retention among Infants and Mothers Effectively (PRIME) study is evaluating the effectiveness of 3 models of health care delivery namely, mother-infant pair clinics, which deliver integrated HIV and non-HIV services, mother-infant pair clinics plus electronic text message (SMS) reminders for mother-infant pairs who miss scheduled eMTCT follow-up clinics, and current standard of care. The primary outcome is "the proportion of HIV+ mothers and/or HIV-exposed infants (HEI) retained in eMTCT care at 12 months postpartum and received recommended HIV and non-HIV services during preceding scheduled visits." This 3-arm cluster randomized intervention study is being implemented in 30 primary health facilities (10 facilities per arm) in Mangochi and Salima districts, Malawi. At each clinic, a total of 41 HIV+ mothers attending maternal and child health services are being recruited and followed up for 18 months postpartum. This article describes the study methodology and interventions, successes and challenges experienced during the first 12 months of study implementation and relevance of study results to Malawi and other countries adopting the Option B+ strategy.

Evaluating the impact of prevention of mother-to-child transmission of HIV in Malawi through immunization clinic-based surveillance.

BACKGROUND: Prevention of mother-to-child transmission of HIV (PMTCT) programs can greatly reduce the vertical transmission rate (VTR) of HIV, and Malawi is expanding PMTCT access by offering HIV-infected pregnant women life-long antiretroviral therapy (Option B+). There is currently no empirical data on the effectiveness of Malawian PMTCT programs. This study describes a surveillance approach to obtain population-based estimates of the VTR of infants <3 months of age in Malawi immediately after the adoption of Option B+. METHODS AND FINDINGS: A sample of caregivers and infants <3 months from 53 randomly chosen immunization clinics in 4 districts were enrolled. Infant dried blood spot (DBS) samples were tested for HIV exposure with an antibody test to determine maternal seropositivity. Positive samples were further tested using DNA PCR to determine infant infection status and VTR. Caregivers were surveyed about maternal receipt of PMTCT services. Of the 5,068 DBS samples, 764 were ELISA positive indicating 15.1% (14.1-16.1%) of mothers were HIV-infected and passed antibodies to their infant. Sixty-five of the ELISA-positive samples tested positive by DNA PCR, indicating a vertical transmission rate of 8.5% (6.6-10.7%). Survey data indicates 64.8% of HIV-infected mothers and 46.9% of HIV-exposed infants received some form of antiretroviral prophylaxis. Results do not include the entire breastfeeding period which extends to almost 2 years in Malawi. CONCLUSIONS: The observed VTR was lower than expected given earlier modeled estimates, suggesting that Malawi's PMTCT program has been successful at averting perinatal HIV transmission. Challenges to full implementation of PMTCT remain, particularly around low reported antiretroviral prophylaxis. This approach is a useful surveillance tool to assess changes in PMTCT effectiveness as Option B+ is scaled-up, and can be expanded to track programming effectiveness for young infants over time in Malawi and elsewhere.

Improving PMTCT uptake and retention services through novel approaches in peer-based family-supported care in the clinic and community: a 3-arm cluster randomized trial (PURE Malawi).

In July 2011, Malawi introduced an ambitious public health program known as "Option B+," which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of clinical stage or CD4 count. Option B+ is expected to have benefits for HIV-infected women, their HIV-exposed infants, and their HIV-uninfected male sex partners. However, these benefits hinge on early uptake of prevention of mother-to-child transmission, good adherence, and long-term retention in care. The Prevention of mother-to-child transmission Uptake and REtention (PURE) study is a 3-arm cluster randomized controlled trial to evaluate whether clinic- or community-based peer support will improve care-seeking and retention in care by HIV-infected pregnant and breastfeeding women, their HIV-exposed infants, and their male sex partners, and ultimately improve health outcomes in all 3 populations. We describe the PURE Malawi Consortium, the initial work conducted to inform the trial and interventions, the trial design, and the analysis plan. We then discuss concerns and expected contributions to Malawi and the region.

Prioritizing the PMTCT implementation research agenda in 3 African countries: INtegrating and Scaling up PMTCT through Implementation REsearch (INSPIRE).

Countries with high HIV prevalence face the challenge of achieving high coverage of antiretroviral drug regimens interventions including for the prevention of mother-to-child transmission of HIV (PMTCT). In 2011, the World Health Organization and the Department of Foreign Affairs, Trade and Development, Canada, launched a joint implementation research (IR) initiative to increase access to effective PMTCT interventions. Here, we describe the process used for prioritizing PMTCT IR questions in Malawi, Nigeria, and Zimbabwe. Policy makers, district health workers, academics, implementing partners, and persons living with HIV were invited to 2-day workshops in each country. Between 42 and 70 representatives attended each workshop. Using the Child Health Nutrition Research Initiative process, stakeholder groups systematically identified programmatic barriers and formulated IR questions that addressed these challenges. IR questions were scored by individual participants according to 6 criteria: (1) answerable by research, (2) likely to reduce pediatric HIV infections, (3) addresses main barriers to scaling-up, (4) innovation and originality, (5) improves equity among underserved populations, and (6) likely value to policy makers. Highest scoring IR questions included health system approaches for integrating and decentralization services, ways of improving retention-in-care, bridging gaps between health facilities and communities, and increasing male partner involvement. The prioritized questions reflect the diversity of health care settings, competing health challenges and local and national context. The differing perspectives of policy makers, researchers, and implementers illustrate the value of inclusive research partnerships. The participatory Child Health Nutrition Research Initiative approach effectively set national PMTCT IR priorities, promoted country ownership, and strategically allocated research resources.

Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi.

OBJECTIVE: To assess the continuity of care and outcome of pediatric HIV prevention, testing, and treatment services, focusing on early infant diagnosis with DNA polymerase chain reaction (PCR). DESIGN: A retrospective observational cohort. METHODS: Maternal HIV antibody, infant HIV DNA PCR test results, and outcome data from HIV-infected infants from the prevention of mother-to-child transmission, early infant diagnosis, and pediatric HIV treatment programs operating in Lilongwe, Malawi, between 2004 and 2008 were collected, merged, and analyzed. RESULTS: Of the 14,669 pregnant women who tested HIV antibody positive, 7875 infants (53.7%) received HIV DNA PCR testing. One thousand eighty-four infants (13.8%) were HIV infected. Three hundred twenty (29.5%) children enrolled into pediatric HIV care, with 202 (63.1%) at the Baylor Center of Excellence. Among these, antiretroviral therapy was initiated on 110 infants (54.5%) whose median age was 9.1 months (interquartile range, 5.4-13.8) and a median of 2.5 months (interquartile range, 1.4-5.2) after HIV clinic registration. Sixty-nine HIV-infected infants (34.2%) died or were lost by December 2008. Initiation of antiretroviral therapy increased the likelihood of survival 7-fold (odds ratio, 7.1; 95% confidence interval, 3.68 to 13.70). CONCLUSIONS: Separate programs for maternal and infant HIV prevention and care services demonstrated high attrition rates of HIV-exposed and HIV-infected infants, elevated levels of mother-to-child transmission, late infant diagnosis, delayed pediatric antiretroviral therapy initiation, and high HIV-infected infant mortality. Antiretroviral therapy increased HIV-infected infant survival, emphasizing the urgent need for improved service coordination and strategies that increase access to infant HIV diagnosis, improve patient retention, and reduce antiretroviral therapy initiation delays.