Evaluating the impact of HIV pre-exposure prophylaxis on pregnancy, infant, and maternal health outcomes in Malawi: PrIMO study protocol.

BACKGROUND: Incident HIV during the perinatal period significantly impedes elimination of Mother-to-Child HIV Transmission (eMTCT) efforts. Pre-Exposure Prophylaxis (PrEP) effectively reduces HIV acquisition, and new agents like injectable Cabotegravir (CAB-LA) offer potential advantages for pregnant and breastfeeding women. The Pregnancy, Infant, and Maternal health Outcomes (PrIMO) study will compare rates of composite adverse pregnancy outcomes, and infant adverse events, growth and neurodevelopment between mother-infant dyads receiving CAB-LA and those receiving oral PrEP in Malawi. METHODS: PrIMO is an observational cohort study involving: (1) the development of a PrEP Pregnancy Registry for longitudinal surveillance of pregnant women on PrEP in Malawi; and (2) the enrolment of a prospective safety cohort of 621 pregnant women initiating oral PrEP or CAB-LA and their subsequent infants. The registry will include all women continuing or initiating PrEP during pregnancy across targeted sites in Lilongwe and Blantyre districts. The safety cohort will enrol a subset of those women and their infants from Bwaila District Hospital in Lilongwe, Malawi. We hypothesize that CAB-LA's safety will be comparable to daily oral PrEP regarding adverse pregnancy outcomes, maternal/infant adverse events, and infant development. Participants in the cohort will choose either oral PrEP or CAB-LA and will be followed until 52 weeks post-delivery. Safety data will be collected from all mother-infant pairs and qualitative interviews will be conducted with a subset of purposively selected women (n = 50) to assess the acceptability of each PrEP modality. DISCUSSION: The PrIMO study will provide critical data on the safety of CAB-LA in pregnant and breastfeeding women and their infants. Results will guide clinical recommendations as the Malawi Ministry of Health prepares for the rollout of CAB-LA to this population. Evaluation of Registry implementation will inform its expansion to a nationwide safety monitoring system for PrEP use during pregnancy, with implications for similar systems in the region. TRIAL REGISTRATION NUMBER: NCT06158126. The study was prospectively registered (5 December 2023) in ClinicalTrials.gov.

Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi.

BACKGROUND: The World Health Organization recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi. METHODS: We utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis-cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to

Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi.

Background: The World Health Organization (WHO) recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries (LMICs) account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi. Methods: We utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis - cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to

Assessing the Adoption, Acceptability and Fidelity of the Alcohol Use Disorders Test for Alcohol Use Disorders screening in HIV Clinics in Malawi.

BACKGROUND: Alcohol use disorders (AUD) are a common cause of poor treatment outcomes among people with HIV (PWH). In Malawi, routine screening for AUD among PWH is unavailable. We piloted the utility of the Alcohol Use Disorders Identification Test (AUDIT) in screening for AUD among PWH and assessed its adoption, acceptability and fidelity in HIV clinics in Malawi. METHODS: We implemented the AUDIT tool at Mchinji, Kapiri and Kochirira hospitals in Mchinji District between April and May 2021. AUD were defined and classified based on WHO classification as low-risk, harmful/hazardous alcohol use or alcohol dependence. We calculated the prevalence of AUD, the proportion of providers who conducted AUD screening (adoption) and the proportion of providers who conducted AUD screening as intended (fidelity) and compared between clinics. Lastly, we assessed acceptability through a survey among providers. RESULTS: Out of 2036 PWH, 875 (43%) were screened for AUD and 51% were female, mean age was 41 years (SD±12) and 338 (39%) had AUD. Adoption was highest at Mchinji (58%) compared to Kapiri (31%) and Kochiria (29%) (P<0.001). Overall Fidelity was 96%, and it was highest at Kapiri (99%) compared to Mchinji (95%) and Kochirira (98%) (P=0.01). AUD screening with AUDIT was highly acceptable as most providers agreed or completely agreed that the AUDIT was important (100%), easy to use (96%), satisfactory (96%), agreed to continue use (61%) and recommended it for other facilities in the district (100%). CONCLUSION: AUD were common among PWH. While the adoption of AUDIT for AUD screening was moderate, acceptability and fidelity were high. The impact of AUD on HIV treatment outcomes needs to be assessed to determine the role of routine AUD screening in HIV clinics in Malawi.

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.

A novel cervical cancer screen-triage-treat demonstration project with HPV self-testing and thermal ablation for women in Malawi: Protocol for a single-arm prospective trial.

Cervical cancer is the leading cause of cancer mortality among Malawian women, despite being preventable through screening and preventive therapy. In 2004, Malawi implemented a national screening program, using visual inspection with acetic acid (VIA) and cryotherapy, but its success has been limited due to equipment and human resources challenges. Since the development of that program, new technologies for screening and treatment that are less resource-intensive and more scalable have become available. GeneXpert systems provide fast, accurate HPV results and are increasingly available in low-income countries. Self-collection for human papillomavirus (HPV) testing is a validated method for screening and improves uptake. Thermal ablation provides an alternative ablative treatment that is simpler to use than cryotherapy and can be performed with portable devices. Meanwhile, urine HPV testing methods provide promising options for primary screening. We designed a single-arm prospective study to investigate a novel HPV screen-triage-treat strategy among 1250 women in Lilongwe, Malawi. Our proposed strategy consists of (1) Xpert HPV testing of self-collected samples, (2) VIA and colposcopy for HPV-positive women, and (3) thermal ablation for HPV-positive/ablation-eligible women. We will collect cervical biopsies, Pap smears, and endocervical samples to validate the HPV results and VIA/colposcopy findings against endpoints of high-grade cervical intraepithelial neoplasia or cancer (CIN2+). We will evaluate same-day completion of our algorithm, its performance in triaging women for treatment, and 24-week treatment efficacy of thermal ablation. We will also explore the performance of HPV and methylation tests in urine samples, as compared to provider- and self-collected cervicovaginal samples.

Prospective Newborn Screening for Sickle Cell Disease and Other Inherited Blood Disorders in Central Malawi.

Objectives: Newborn screening in the United States and Europe allows early identification of congenital disorders but does not yet exist in most low-resource settings, especially in sub-Saharan Africa. Newborn screening can identify multiple inherited hematological disorders, but feasibility and effectiveness for Africa are not fully determined. Methods: Surplus dried blood spot collected in Central Malawi through the HIV Early Infant Diagnosis surveillance program were repurposed and tested by isoelectric focusing for sickle cell disease and trait. Additional genetic testing identified G6PD deficiency and alpha thalassemia. Results: Testing of 10,529 cards revealed an overall sickle cell trait prevalence of 7.0% (range 3.9-9.7% by district); 10 of 14 infants identified with sickle cell disease (prevalence 0.1%) were located and received care at a specialized clinic. Subsequent testing of 1,329 randomly selected cards identified alpha thalassemia trait in 45.7% of samples, and G6PD deficiency in 20.4% of males and 3.4% of females, with 29.0% of females as heterozygous carriers. Conclusion: Inherited hematological disorders are common in Central Malawi; early identification through newborn screening can improve clinical outcomes and should be supported throughout Africa.