OPTION B+ IN MALAWI: ANTIRETROVIRAL THERAPY FOR PREVENTION OF MOTHER-TO-CHILD HIV TRANSMISSION AND ITS EFFECTS ON PRETERM BIRTH AND FEMALE-TO-MALE HIV TRANSMISSION

Maganizo B. Chagomerana: Option B+ in Malawi: Antiretroviral therapy for prevention of mother-to-child HIV transmission and its effects on preterm birth and female-to-male HIV transmission (Under the direction of Kimberly A. Powers) Large number of new and prevalent HIV infections among reproductive-aged women in sub-Saharan Africa makes prevention of mother-to-child HIV transmission (PMTCT) a major public health priority. Option B+ is a simplified approach to PMTCT that recommends universal life-long ART for pregnant and breastfeeding women regardless of HIV disease stage or CD4 count. This approach is expected to help bring an end to new pediatric HIV infections and substantially improve maternal health in settings with high HIV burdens. However, the effect of ART initiation during pregnancy in the Option B+ era on birth outcomes and female-to-male HIV transmission is not well known. We used maternity-ward data from Bwaila Hospital in Lilongwe, Malawi to estimate the risk of preterm birth among HIV-infected women. The risk of preterm birth was similar in women who had initiated ART at any point prior to delivery compared to those who never initiated ART (adjusted Risk Ratio (aRR) = 0.88; 95% CI: 0.65 – 1.19). No clear trend between timing of ART and risk of preterm birth was observed. ART initiation at any point before delivery was strongly protective against extremely to very preterm birth (27 – 32 weeks gestation) (aRR = 0.43; 95% CI: 0.26 – 0.72) Using mathematical modeling we estimated the female-to male HIV infections using two PTMTC approaches, Option B and Option B+ in the period 2011 - 2020. The estimated relative incidence (RI) under Option B+ was 4% lower (median RI = 0.96; 95% CI: 0.94 – 0.97) in 2015 and was projected to be 7% lower (median RI = 0.93; 95% CI: 0.90 – 0.95) by 2020 compared to the Option B in which ART uptake values in the period 2011-2020 assumed to be the same for Option B as those assumed for Option B+. When Option B ART uptake values in the period 2011-2020 were assumed to remain at 2011 levels, the estimated RI under Option B+ was 14% lower (median RI = 0.86; 95% CI: 0.84 – 0.88) in 2015 and was projected to be 21% lower (median RI = 0.79; 95% CI: 0.74 – 0.83) by 2020.Doctor of Philosoph

PMTCT option b+ does not increase preterm birth risk and may prevent extreme prematurity: A retrospective cohort study in Malawi

Objective: To estimate preterm birth risk among infants of HIV-infected women in Lilongwe, Malawi, according to maternal antiretroviral therapy (ART) status and initiation time under Option B+. Design: A retrospective cohort study of HIV-infected women delivering at ≥27 weeks of gestation, April 2012 to November 2015. Among women on ART at delivery, we restricted our analysis to those who initiated ART before 27 weeks of gestation. Methods: We defined preterm birth as a singleton live birth at ≥27 and <37 weeks of gestation, with births at <32 weeks classified as extremely to very preterm. We used log-binomial models to estimate risk ratios and 95% confidence intervals for the association between ART and preterm birth. Results: Among 3074 women included in our analyses, 731 preterm deliveries were observed (24%). Overall preterm birth risk was similar in women who had initiated ART at any point before 27 weeks and those who never initiated ART (risk ratio = 1.14; 95% confidence interval: 0.84 to 1.55), but risk of extremely to very preterm birth was 2.33 (1.39 to 3.92) times as great in those who never initiated ART compared with those who did at any point before 27 weeks. Among women on ART before delivery, ART initiation before conception was associated with the lowest preterm birth risk. Conclusions: ART during pregnancy was not associated with preterm birth, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth. As preconception ART initiation appears especially protective, long-term retention on ART should be a priority to minimize preterm birth in subsequent pregnancies

HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children

This work was supported by grants from the NIH (T.E.T., 5R01AI034969-14) and a Clinical Fellowship from The Wellcome Trust, United Kingdom (C.A.M, 88758). The Malawi-Liverpool-Wellcome Clinical Research Programme is supported by core funding from The Wellcome Trust, UK.Objectives. Study of the effect of HIV on disease progression in heterogeneous severe malaria syndromes with imprecise diagnostic criteria has led to varying results. Characteristic retinopathy refines cerebral malaria (CM) diagnosis, enabling more precise exploration of the hypothesis that HIV decreases the cytokine response in CM, leading to higher parasite density and a poor outcome. Methods. We retrospectively reviewed data on clinical progression and laboratory parameters in 877 retinopathy-positive CM cases admitted 1996-2011 (14.4% HIV-infected) to a large hospital in Malawi. Admission plasma levels of TNF, interleukin-10, and soluble intercellular adhesion molecule (sICAM-1) were measured by ELISA in 135 retinopathy-positive CM cases. Results. HIV-infected CM cases had lower median plasma levels of TNF (p=0.008), interleukin-10 (p=0.045) and sICAM-1 (p=0.04) than HIV-uninfected cases. Although HIV-infected children were older and more likely to have co-morbidities, HIV-status did not significantly affect parasite density (p=0.90) or outcome (24.8% infected, vs. 18.5% uninfected; p=0.13). Conclusions. In this well-characterised CM cohort, HIV-coinfection was associated with marked blunting of the inflammatory response but did not affect parasite density or outcome. These data highlight the complex influence of HIV on severe malaria and bring into question systemic inflammation as a primary driver of pathogenesis in human CM.Publisher PDFPeer reviewe

Using routinely collected blood donation data for expanded HIV and syphilis surveillance in Blantyre District, Malawi

BACKGROUND: WHO recommends all blood donations be screened for transfusion transmissible infections. However, these data are not incorporated into national surveillance systems in Malawi. We set out to use routinely collected data from blood donors in Blantyre district, Malawi, an area of high HIV and syphilis prevalence, to explore current HIV and syphilis prevalence and identify recent sero-conversions among repeat donors. METHODS: We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service (MBTS) between October 1st 2015 and May 31st 2021. All blood donations were routinely screened for WHO-prioritized transfusion-transmissible infections, including HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative. Logistic regression was used to model the impact of individual level covariates on the probability of sero-conversion. RESULTS: A total of 93,199 donations from 5,054 donors were recorded, with 7 donors (0.1%) donating a maximum of 24 times. The majority of donors were male (4,294; 85%) and students (3264; 64.6%) at the time of their first donation. Of those screened for HIV and syphilis, 126 (2.5%, 126/5,049) and 245 (4.9%, 245/5,043) tested positive respectively.Among repeat donors who previously tested negative, 87 HIV sero-conversions and 195 syphilis sero-conversions were identified over the study period, indicating an HIV incidence rate of 6.86 per 1,000 person-years and a syphilis incidence rate of 15.37 per 1,000 person-years. Donors who were female or aged 16-19 at the time of first donation had a higher risk of HIV or syphilis sero-conversion. CONCLUSIONS: Routinely collected data from national blood donation services may be used to enhance existing population-level disease surveillance systems, particularly in high prevalence areas. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify and characterise blood donor populations at increased risk of sero-conversion over the study period. This information will provide insight into priority prevention areas in Blantyre district and help to inform targeted interventions for improved prevention, testing and treatment

RTS,S vaccination is associated with reduced parasitemia and anemia among children diagnosed with malaria in the outpatient department of a district hospital in rural Malawi

The RTS,S/AS01 malaria vaccine was recently approved by the World Health Organization, but real-world effectiveness is still being evaluated. We measured hemoglobin concentration and parasite density in vaccinated and unvaccinated children who had been diagnosed with malaria by rapid diagnostic test (mRDT) in the outpatient department of a rural hospital in Malawi. Considering all mRDT positive participants, the mean hemoglobin concentration among unvaccinated participants was 9.58 g/dL. There was improvement to 9.82 g/dL and 10.36 g/dL in the 1 or 2 dose group (p = 0.6) and the 3 or 4 dose group (p = 0.0007), respectively. Among a microscopy positive subset of participants, mean hemoglobin concentration of unvaccinated participants was 9.55 g/dL with improvement to 9.82 g/dL in the 1 or 2 dose group (p = 0.6) and 10.41 g/dL in the 3 or 4 dose group (p = 0.003). Mean parasite density also decreased from 115,154 parasites/μL in unvaccinated children to 87,754 parasites/μL in children who had received at least one dose of RTS,S (p = 0.04). In this study population, vaccination was associated with significant improvements in both hemoglobin concentration and parasite density in the setting of real-world administration of the RTS,S/AS01 vaccine

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

‘If I am on ART, my new-born baby should be put on treatment immediately’: Exploring the acceptability, and appropriateness of Cepheid Xpert HIV-1 Qual assay for early infant diagnosis of HIV in Malawi

Early infant diagnosis of HIV (EID-HIV) is key to reducing paediatric HIV mortality. Traditional approaches for diagnosing HIV in exposed infants are usually unable to optimally contribute to EID. Point-of-care testing such as Cepheid Xpert HIV-1 Qual assay-1 (XPertHIV) are available and could improve EID-HIV in resource constrained and high HIV burden contexts. We investigated the acceptability and perceived appropriateness of XpertHIV for EID-HIV in Mulanje Hospital, Malawi. Qualitative cross-sectional study using semi-structured interviews (SSI) among caregivers and health care workers at Mulanje District Hospital. The qualitative study was nested within a larger diagnostic study that evaluated the performance of XpertHIV using whole-blood-sample in a resource limited and high burden setting. A total of 65 SSIs were conducted among caregivers (n = 60) and health care providers (n = 5). Data were coded using deductive and inductive approaches while thematic approach was used to analyse data. Point-of-care XPertHIV was perceived to be acceptable among caregivers and health care providers. Caregivers’ motivations for accepting XPertHIV HIV-testing for their infants included perceived risk of HIV emanating from child’s exposure and validation of caregiver’s own HIV sero-status. Although concerns about pain of testing and blood sample volumes taken from an infant remained amplified, overall, both caregivers and health care providers felt XpertHIV was appropriate because of its quick result turn-around-time which decreased anxiety and stress, the prospect of early treatment initiation and reduction in hospital visits and related costs. Implementation of XpertHIV has a great potential to improve EID-HIV in Malawi because of its quick turn-around-time and associated benefits including overcoming access-related barriers. Scaled implementation of this diagnostic technology require a robust community engagement strategy for managing caregivers and community myths and misconceptions towards the amount of blood sample collected from infants

Update on pathology laboratory development and research in advancing regional cancer care in Malawi

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs

Are venue-based strategies the ticket to the last mile in HIV prevention in Malawi

Background: In 2016, Blantyre District had the highest adult HIV prevalence in Malawi (17% overall; 22% in women) and the lowest viral suppression rate (60%). In response, the MOH expanded prevention and treatment strategies. We hypothesized that social venues patronized by people with high sexual partnerships rates could identify sub-groups currently missed. Methods: We conducted cross-sectional bio-behavioral surveys of representative samples of individuals seeking care in government clinics (n=2313) and social venue patrons (n=1802) Jan-Mar 2022. Clinics were randomly selected from government clinics providing HIV testing. Venues were randomly sampled from urban and rural strata with oversampling of rural venues. Sampling weights were based on 2-stage sampling probabilities. We followed national testing protocols for rapid tests, recency testing and viral load measurements. Acute infections were identified by pooling dried blood spots from persons with an HIV- rapid test. Results: Compared to the clinic population, the venue population was more likely to: be male (68% vs 28%); aged >25 years (61% vs 51%); unmarried (62% vs 40%); drink alcohol daily (43% vs 8%); have more sexual partners in the last year (mean 16 vs 2); report a new sex partner in the past 4 weeks (42% vs 14%); and report transactional sex (52% vs 12%). HIV prevalence (Table 1) was higher among the venue population (19% vs 9%); the proportion HIV+ suppressed was similar (78%). Among women recruited at venues, prevalence increased by age: 0% among age 15-17 to 41% among age 18-21. At venues, factors associated with HIV infection include female sex (39% vs 10%); having a new partner in the past 4 weeks (28% vs 13%) and transactional sex (25% vs 13%). Acute and recent infections were uncommon. Clinic participants who reported visiting venues were less likely to have a suppressed viral load than other PLHIV clinic participants (53% vs 81%). Among both populations, reporting a genital sore in the past 4 weeks was associated with non-suppression (40% vs 20% in clinic; 48% vs 20% in venues). Conclusions: Lower HIV prevalence and greater viral suppression suggests that Blantyre’s HIV epidemic is slowing. Strategies to further reduce transmission should include outreach to venues with higher prevalence of unsuppressed infection and to young women at venues. Testing for acute or recent infection yielded few cases and thus did not provide sufficient value to warrant the cost

Results from Two HPV-Based Cervical Cancer Screening-Family Planning Integration Models in Malawi: A Cluster Randomized Trial

We conducted a cluster randomized trial of two models for integrating HPV self-collection into family-planning (FP) services at 16 health facilities in Malawi between March 2020–December 2021. Model 1 involved providing only clinic-based HPV self-collection, whereas Model 2 included both clinic-based and community-based HPV self-collection. An endline household survey was performed in sampled villages and households between October-December 2021 in the catchment areas of the health facilities. We analyzed 7664 surveys from 400 villages. Participants from Model 2 areas were more likely to have ever undergone cervical cancer screening (CCS) than participants from Model 1 areas, after adjusting for district, facility location (urban versus rural), and facility size (hospital versus health center) (adjusted odds ratio = 1.73; 95% CI: 1.29, 2.33). Among participants who had ever undergone CCS, participants from Model 2 were more likely to report having undergone HPV self-collection than participants from Model 1 (50.5% versus 22.8%, p = 0.023). Participants from Model 2 were more likely to be using modern FP (adjusted odds ratio = 1.01; 95% CI: 1.41, 1.98) than Model 1 participants. The integration of FP and HPV self-collection in both the clinic and community increases CCS and modern FP uptake more than integration at the clinic-level alone