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.

Re-engagement and retention in HIV care after preventive default tracking in a cohort of HIV-infected patients in rural Malawi: A mixed-methods study.

Loss-to-follow-up (LTFU) in the era of test-and-treat remains a universal challenge, especially in rural areas. To mitigate LTFU, the HIV program in Neno District, Malawi, utilizes a preventive default tracking strategy named Tracking for Retention and Client Enrollment (TRACE). We utilized a mixed-methods descriptive study of the TRACE program on patient's re-engagement and retention in care (RiC). In the quantitative arm, we utilized secondary data of HIV-infected patients in the TRACE program from January 2018 to June 2019 and analyzed patients' outcomes at 6-, 12-, and 24-months post-tracking. In the qualitative arm, we analyzed primary data from 25 semi-structured interviews. For the study period, 1028 patients were eligible with median age was 30 years, and 52% were women. We found that after tracking, 982 (96%) of patients with a 6-week missed appointment returned to care. After returning to care, 906 (88%), 864 (84%), and 839 (82%) were retained in care respectively at 6-,12-, and 24-months. In the multivariate analysis, which included all the covariates from the univariate analysis (including gender, BMI, age, and the timing of ART initiation), the results showed that RiC at 6 months was linked to WHO stage IV at the start of treatment (with an adjusted odds ratio (aOR) of 0.18; 95% confidence interval (CI) of 0.06-0.54) and commencing ART after the test-and-treat recommendation (aOR of 0.08; 95% CI: 0.06-0.18). RiC after 12 months was associated with age between 15 and 29 years (aOR = 0.18; 95%CI: 0.03-0.88), WHO stage IV (aOR = 0.12; 95%CI: 0.04-0.16) and initiating ART after test-and-treat recommendations (aOR = 0.08; 95%CI: 0.04-0.16). RiC at 24 months post-tracking was associated with being male (aOR = 0.61; 95%CI: 0.40-0.92) and initiating ART after test-and-treat recommendations (aOR = 0.16; 95%CI:0.10-0.25). The qualitative analysis revealed that clarity of the visit's purpose, TRACE's caring approach changed patient's mindset, enhanced sense of responsibility and motivated patients to resume care. We recommend integrating tracking programs in HIV care as it led to increase patient follow up and patient behavior change.

Impact of a teen club model on HIV outcomes among adolescents in rural Neno district, Malawi: a retrospective cohort study.

OBJECTIVE: To compare the impact of a teen club model to the standard care model on HIV treatment outcomes among adolescents (10-19 years of age). DESIGN: Retrospective cohort study. SETTING: HIV clinics in Neno district, Malawi. PARTICIPANTS: Adolescents living with HIV enrolled in teen clubs (n=235) and matched participants in standard HIV care (n=297). OUTCOME MEASURES: Attrition from HIV care, defined as a combination of treatment outcomes 'died', 'defaulted' and 'transferred out'. RESULTS: Over a 4-year follow-up period, adolescents who participated in the teen club had a significantly higher likelihood of remaining in care than those who did not (HR=2.80; 95% CI: 1.46 to 5.34). Teen clubs also increased the probability of having a recent measured viral load (VL) and BMI, but did not change the probability of VL suppression. The age at antiretroviral treatment initiation below 15 years (aHR=0.37; 95% CI: 0.17 to 0.82) reduced the risk of attrition from HIV care, while underweight status (aHR=3.18; 95% CI: 1.71 to 5.92) increased the risk of attrition, after controlling for sex, WHO HIV staging and teen club participation. CONCLUSIONS: The teen club model has the potential to improve treatment outcomes among adolescents in rural Neno district. However, in addition to retaining adolescents in HIV care, greater attention is needed to treatment adherence and viral suppression in this special population. Further understanding of the contextual factors and barriers that adolescents in rural areas face could further improve the teen club model to ensure high-quality HIV care and quality of life.

Near Point-of-Care HIV Viral Load: Targeted Testing at Large Facilities.

INTRODUCTION: Point-of-care (POC) technologies in resource-limited settings can circumvent challenges of centralized laboratory testing, improving clinical management. However, higher device costs and uncertain indications for use have inhibited scaling up POC modalities. To address this gap, we investigated the feasibility and cost of targeted near-POC viral load (VL) testing in 2 large HIV clinics in Lilongwe, Malawi. METHODS: VL testing using GeneXpert was targeted for patients suspected of treatment failure or returning to care after a previously elevated VL (>1000 copies/mL). Descriptive analysis of retrospective clinical and cost data is presented. RESULTS: Two thousand eight hundred thirteen near-POC VL tests were conducted. One thousand five hundred eleven (54%) tests were for patients for whom results and reason for the test were documented: 57% (794/1389) of tests were to confirm a previously high VL, and 33% (462/1389) were due to clinical indications. Sixty-one percent (926/1511) of patients had a high VL, of whom 78% (719/926) had a recorded clinical action: 77% (557/719) switched to second line antiretroviral therapy, and 15% (194/719) were referred for intensive adherence counseling. Eighty-two percent (567/687) of patients received a clinical action on the same day as testing. The "all-in" cost was $33.71 for a valid POC VL test, compared with an international benchmark for a centralized VL test of $28.62. CONCLUSION: Targeted, near-POC VL testing was feasible and consistently enabled prompt clinical action. The difference between the "all-in" cost of near-POC VL and centralized testing of $5.09 could be further reduced in an optimized national program by combining targeted near-POC testing and centralized testing.

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+.

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.