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Abstract Background The sub-Saharan African Regional Partnership for mental health and capacity building (SHARP) study was a clinic-randomized trial of two implementation strategies for integrating depression screening and treatment into non-communicable diseases’ (NCD) clinics in Malawi between 2019 and 2022. We report on the barriers to implementing depression care integration at SHARP study sites and potential solutions. Methods N = 39 in-depth interviews with participants from all ten sites were conducted, recorded, transcribed, coded in NVivo 12 and analyzed by qualitative experts. We used thematic analysis to identify implementation challenges and potential solutions. The Consolidated Framework for Implementation Research helped to develop guides and organize the results. Results Outer setting barriers included high workload (due to high patient volume, increased paperwork, shortage of staff), the effects of coronavirus disease 2019 (COVID-19) pandemic, staff turnover and negative provider attitudes. Limited clinic space arose as an inner setting barrier. Workload can be overcome by increasing the number of NCD personnel, decentralizing the depression/NCD services and integrating mental health and NCD documents (implementation process). The COVID-19 pandemic presented unique challenges including fear of interpersonal contact and changes in scheduling staff that were difficult to overcome in the short term. To deal with the effects of staff turnover, participants identified the need for continuous depression training to new providers. Lobbying for more rooms from leadership can address concerns of limited space. To reduce negative provider attitudes, participants urged facility leadership to make themselves available for consultations and mentorship and to provide continuous learning opportunities such as refresher trainings. Conclusion The experience in the SHARP study highlights the need for a culture of continuous learning and adaptation in healthcare settings, enabling the development of strategies to overcome evolving challenges. Planning for the integration of mental health and NCD care should extend beyond immediate challenges and consider long-term goals and sustainability. Trial registration This study reports part of the findings from the endpoint evaluation of the SHARP clinical trial that is registered at ClinicalTrials.gov, NCT03711786 first posted 20,181,018.

Abstract Introduction Disengagement from HIV care during the perinatal period remains a challenge. Improving engagement in HIV care requires monitoring engagement across multiple indicators, including retention in HIV care, visit adherence, clinic transfers, and viral suppression to support improved clinical and programmatic outcomes. Methods We enrolled a prospective cohort of pregnant WHIV across a network of five urban clinics in Lilongwe, Malawi from February 2020-February 2021. WHIV were followed from their first antenatal care visit through 9 months postpartum across all study sites using biometric fingerprint scanning. Study visits occurred at enrollment into antenatal care, 6 weeks’, 6 months, and 9 months postpartum. In addition, all usual care HIV visits were captured via medical records. Participants who missed a study visit or usual care visit were traced. We evaluated determinants of multiple indicators of engagement in care, including retention in HIV care (attending a scheduled visit or self-reported recent visit when traced), HIV visit adherence (missed scheduled HIV visits and HIV visit coverage), clinic transfers, and viral load suppression (

Summary: Background: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. Methods: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. Findings: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61–2.44) and 3.40% (95% CI 2.30–4.49) for COVID-19, and 0.048% (95% CI 0.00–0.10) and 0.32% (95% CI 0.59–0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44–0.77; p

IntroductionUptake of voluntary medical male circumcision (VMMC) remains a challenge in many settings. Innovative implementation strategies are required to scale-up VMMC uptake.MethodologyRITe was a multi-faceted intervention comprising transport reimbursement (R), intensified health education (IHE) and SMS/Telephone tracing (Te), which increased the uptake of VMMC among uncircumcised men with sexually transmitted infections (STIs) in Malawi. Using a concurrent exploratory mixed-method approach, we assessed the intervention's acceptability, feasibility and appropriateness among men with STIs and healthcare workers (HCWs) at Bwaila District Hospital. Participants completed Likert scale surveys and participated in-depth interviews (IDIs) and focus group discussions (FGDs). We calculated percentages of responses to survey items and summarized common themes using thematic analysis. Median scores and interquartile ranges (IQR) were calculated for acceptability, feasibility and appropriateness of each strategy at baseline and end-line and compared using the Wilcoxon signed rank test.ResultsA total of 300 surveys, 17 IDIs and 4 FGDs were conducted with men and HCWs between baseline and end-line. The mean age for men in the survey was 29 years (SD ±8) and most were married/cohabiting (59.3%). Mean age for HCWs was 38.5 years (SD ±7), and most were female (59.1%). For acceptability, participants agreed that RITe was welcome, approvable, and likable. Despite participants agreeing that RITe was a good idea, fit and suitability influenced appropriateness, particularly at baseline, which improved at end-line for Te and R. For feasibility, HCWs agreed that RITe was easy to implement, but expressed concerns that R (end-line median = 4, IQR: 2, 4) and Te (end-line median = 4, IQR: 4, 4), were unsustainable. Interviews corroborated the survey results. Participants reported that IHE provided important information, Te was a good reminder and R was attractive, but they reported barriers to R and Te such as electricity, limited access to phones and distrust in the government.ConclusionsThe RITe intervention was acceptable, feasible and appropriate. However, culture/religion and structural barriers affected perceptions of appropriateness and feasibility, respectively. Continued awareness raising on VMMC and addressing setting-specific structural factors are required to overcome barriers that impede demand-creation interventions for VMMC.

Abstract Introduction Long‐acting injectable cabotegravir (CAB‐LA) for pre‐exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB‐LA pharmacokinetics in pregnant women during the blinded period of HPTN 084. Methods Participants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open‐label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion

Abstract 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.

Abstract Option B + provides lifelong ART to pregnant and breastfeeding women with HIV to reduce mother-to-child transmission of HIV (eMTCT) and improve maternal health. The effectiveness of Option B + relies on continuous engagement, but suboptimal monitoring of HIV care hinders our measurements of engagement. Process mapping and quality improvement (PROMAQI) is a quality improvement strategy for healthcare workers (HCWs) to optimize complex processes such as monitoring HIV care. We assessed the acceptability and feasibility of the PROMAQI among HCWs and identified barriers and facilitators for PROMAQI implementation. A cross-sectional study using a mixed method approach was conducted from August 2021 to March 2022 across five urban health facilities participating in PROMAQI implementation n the Lilongwe district, Malawi. We assessed PROMAQI acceptability and feasibility at the end of the study. A 5-point Likert (1 = worst to 5 = best) scale tool was administered to 110 HCWs (n = 15–33 per facility) involved in PROMAQI implementationThese data were analysed using descriptive statistics Among the 110 HCWs, twenty-two (QI team (n = 11) and QI implementers (n = 11)) were purposively selected for in-depth interviews. Thematic analysis was conducted using deducted and inductive approaches. The theoretical framework for acceptability (TFA) was used to identify reasons for acceptability. The Consolidated Framework for Implementation Research (CFIR) was used to characterize the barriers and facilitators of PROMAQI implementation. HCWs recruited had a median age of 37 (32–43) years, 82.0% of whom were female. Most (42%) had completed secondary education, and 84% were nurses and community health workers. The median (IQR) acceptability and feasibility scores for the PROMAQI were 5 (IQR 4–5) and 4 (IQR 4–5), respectively. Reasons for high PROMAQI acceptability included addressing a relevant gap and improving performance. Perceived implementation barriers included poor work attitudes, time constraints, resource limitations, knowledge gaps, and workbook difficulties. The facilitators included communication, mentorship, training, and financial incentives. PROMAQI is a highly acceptable and feasible tool for monitoring engagement of women in Option B + . Addressing these barriers may optimize the implementation of PROMAQI. Scaling up PROMAQI may enhance retention in the Option B + program and facilitate eMTCT.

Background Option B+ aims to prevent mother-to-child transmission of HIV by providing lifelong antiretroviral therapy (ART) to pregnant and breastfeeding women living with HIV (PBWHIV). Identifying and reengaging PBWHIV who disengage or fail to initiate ART is essential for the success of Option B+. However, the process is often suboptimal, leading to challenges such as misclassification of patients as lost to follow-up. Healthcare workers (HCWs) are pivotal for monitoring engagement, but little is known about their monitoring practices. This study aimed to explore how HCWs monitor women's engagement in Option B+ services. Methods A qualitative study was conducted in five high-volume health facilities in Lilongwe, Malawi. Thirty HCWs responsible for monitoring women in Option B+ were purposively selected as key informants. Semistructured interviews were conducted between March and June 2021. Thematic analysis employing deductive and inductive coding methods was utilized. The Consolidated Framework for Implementation Research was used to map gaps, strategies, barriers, and facilitators of monitoring. Results Monitoring was described as tracking a PBWHIV from HIV diagnosis to initiation of ART to subsequent ART visits for up to 2 years postpartum. The gaps included timing variations in tracing. No procedures to follow up formal transfer-outs or management of silent transfers during emergency ART refills were identified. Strategies identified included interfacility collaboration, record review, tracing, escorting women during initial visits, and self-reports. Technological innovations, such as WhatsApp groups, were highlighted as game changers in interfacility collaboration when tracking women's movements. Barriers included resource constraints (human and operational), poor work attitudes, and challenges faced by women (partner support, stigma, and HCW rapport). The facilitators included implementing partner support, leadership, and strategies such as education and tracing. Conclusion Addressing resource constraints, women's relationship dynamics for self-management, HCWs’ attitudes, and standardizing tracing protocols are crucial for effective monitoring. Leveraging instant messaging for clinic coordination may enhance tracing. Further research and interventions should target identified gaps to promote effective monitoring in similar settings.

Abstract Introduction Antiretroviral therapy (ART) initiation in infants living with HIV before 12 weeks of age can reduce the risk of mortality by 75%. Point‐of‐care (POC) diagnostic testing is critical for prompt ART initiation; however, despite its availability, rates of ART initiation are still relatively low before 12 weeks of age. This systematic review describes the barriers to ART initiation in infants before 12 weeks of age, despite the availability of POC. Methods This systematic review used a narrative synthesis methodology. We searched PubMed and Scopus using search strategies that combined terms of multiple variants of the keywords “early infant initiation on antiretroviral therapy,” “barriers” and “sub‐Saharan Africa” (initial search 18th January 2023; final search 1st August 2023). We included qualitative, observational and mixed methods studies that reported the influences of early infant initiation on ART. We excluded studies that reported influences on other components of the Prevention of Mother to Child Transmission cascade. Using a deductive approach guided by the updated Consolidated Framework of Implementation Research, we developed descriptive codes and themes around barriers to early infant initiation on ART. We then developed recommendations for interventions for the identified barriers using the action, actor, target and time framework from the codes. Results Of the 266 abstracts reviewed, 52 full‐text papers were examined, of which 12 papers were included. South Africa had most papers from a single country (n = 3) and the most reported study design was retrospective (n = 6). Delays in ART initiation beyond 12 weeks in infants 0–12 months were primarily associated with health facility and maternal factors. The most prominent barriers identified were inadequate resources for POC testing (including human resources, laboratory facilities and patient follow‐up). Maternal‐related factors, such as limited male involvement and maternal perceptions of treatment and care, were also influential. Discussion We identified structural barriers to ART initiation at the health system, social and cultural levels. Improvements in the timely allocation of resources for POC testing operations, coupled with interventions addressing social and behavioural barriers among both mothers and healthcare providers, hold a promise for enhancing timely ART initiation in infants. Conclusions This paper identifies barriers and proposes strategies for timely ART initiation in infants.

Abstract Background Low- and middle-income countries often lack access to mental health services, leading to calls for integration within other primary care systems. In sub-Saharan Africa, integration of depression treatment in non-communicable disease (NCD) settings is feasible, acceptable, and effective. However, leadership and implementation climate challenges often hinder effective integration and quality of services. The aim of this study was to identify discrete leadership strategies that facilitate overcoming barriers to the integration of depression care in NCD clinics in Malawi and to understand how clinic leadership shapes the implementation climate. Methods We conducted 39 in-depth interviews with the District Medical Officer, the NCD coordinator, one NCD provider, and the research assistant from each of the ten Malawian NCD clinics (note one District Medical Officer served two clinics). Based on semi-structured interview guides, participants were asked their perspectives on the impact of leadership and implementation climate on overcoming barriers to integrating depression care into existing NCD services. Thematic analysis used both inductive and deductive approaches to identify emerging themes and compare among participant type. Results The results revealed how engaged leadership can fuel a positive implementation climate where clinics had heightened capacity to overcome implementation barriers. Effective leaders were approachable and engaged in daily operations of the clinic and problem-solving. They held direct involvement with and mentorship during the intervention, providing assistance in patient screening and consultation with treatment plans. Different levels of leadership utilized their respective standings and power dynamics to influence provider attitudes and perceptions surrounding the intervention. Leaders acted by informing providers about the intervention source and educating them on the importance of mental healthcare, as it was often undervalued. Lastly, they prioritized teamwork and collective ownership for the intervention, increasing provider responsibility. Conclusion Training that prioritizes leadership visibility and open communication will facilitate ongoing Malawi Ministry of Health efforts to scale up evidence-based depression treatment within NCD clinics. This proves useful where extensive and external monitoring may be limited. Ultimately, these results can inform successful strategies to close implementation gaps to achieve integration of mental health services in low-resource settings through improved leadership and implementation climate. Trial registration These findings are reported from ClinicalTrials.gov, NCT03711786. Registered on 18/10/2018. https://clinicaltrials.gov/ct2/show/NCT03711786 .

Abstract Background Dyslipidaemia among individuals with diabetes is a significant modifiable risk factor for atherosclerotic cardiovascular diseases (ASCVDs). ASCVDs are a major cause of mortality and morbidity globally, especially in people with diabetes. In Malawi, limited data exist on the prevalence and biochemical characteristics of diabetic dyslipidaemia. This study investigated the prevalence and biochemical characteristics of dyslipidaemia in individuals attending the diabetes clinic at Kamuzu Central Hospital, the largest tertiary referral hospital in Central Malawi. Methods Using a cross-sectional design, sociodemographic, medical and anthropometric data were collected from 391 adult participants who were enrolled in the study. Blood samples were analysed for glycosylated haemoglobin (HBA1c) and fasting lipid profiles. The prevalence of dyslipidaemia was calculated, and the biochemical characteristics of the dyslipidaemia were defined. The associations between dyslipidaemia and risk factors such as sociodemographic characteristics, obesity, and HBA1c levels were evaluated using logistic regression analysis. Results Prevalence of dyslipidaemia was observed in 71% of the participants, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality among the study participants. None of the participants were receiving any lipid-lowering therapy. On bivariate analysis, dyslipidemia was positively associated with female sex [OR 1.65 (95% CI 1.05- 2.58); p = 0.09], age ≥ 30 years [OR 3.60 (95% CI 1.17-7.68); p = 0.001] and overweight and obesity [OR 2.11 (95% CI 1.33-3.34); p = 0.002]. On multivariate analysis, being overweight or obese was an independent predictor of dyslipidaemia [AOR 1.8;(95% CI 1.15- 3.37); p = 0.04]. Conclusion Dyslipidaemia was highly prevalent among individuals with diabetes in this study, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality. Overweight and obesity were also highly prevalent and positively predicted dyslipidaemia. This study highlights the importance of appropriately addressing dyslipidaemia, overweight and obesity among individuals with diabetes in Malawi and other similar settings in Africa as one of the significant ways of reducing the risk of ASCVDs among this population.

Abstract Background Option B + offers lifelong ART to pregnant or breastfeeding mothers, but postpartum loss to HIV care, partially driven by perinatal depression (PND), threatens the impact of this policy. This study aims to understand women’s and providers’ preferences for developing a feasible intervention to address PND and support engagement in HIV care among women living with PND and HIV. Methods We conducted a total of 6 focus group discussions (FGDs) involving 4 clinics in Lilongwe District from December 2018 through February 2019. We conducted 2 FGDs each among 3 stakeholder groups: clinical staff, prenatal women, and postnatal women. Perinatal participants were living with HIV and screened positively for PND using the validated Edinburgh Postnatal Depression Scale (EPDS). Clinical staff were nurses who were trained antiretroviral therapy (ART) providers. Interviewers led FGDs in Chichewa using a semi-structured guide. Data were analyzed using deductive and inductive coding in NVivo 12 software. Results Women favored ART linkage services, but providers said they already offered such services, with mixed results. Individual counselling was universally supported. A perceived benefit of group counselling was peer support, but there were concerns among women regarding confidentiality and stigma. Women liked mobile appointment reminders but identified low phone ownership as a barrier. Participants recommended home visits as an additional care engagement strategy. Women consistently discussed the need for social support from family members and friends to address PND and support engagement in HIV care. Conclusion This study highlights the importance of peer encouragement to support perinatal HIV care engagement among women with HIV and PND. The results from this study can be used to support intervention development to increase HIV care engagement and improve long-term HIV outcomes in women with PND.

Abstract Introduction In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients’ experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi. Methods Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient’s perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction. Results Most women in both groups were well versed on DTG’s potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures. Conclusion DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.

[This corrects the article DOI: 10.1371/journal.pone.0279619.].

Abstract Introduction Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi’s Option B + program. Methods We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. Results Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32–1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58–9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. Conclusion Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.

Objective To evaluate the effect a multistrategy demand-creation and linkage intervention on voluntary medical male circumcision (VMMC) uptake, time to VMMC and predictors of VMMC uptake among men with sexually transmitted infections (STIs).Design Pragmatic preinterventional and postinterventional quasi-experimental study combined with a prospective observational design.Setting A public and specialised STI clinic in Lilongwe, Malawi.Population Uncircumcised men who presented to the STI clinic.Methods and intervention The intervention consisted of transport reimbursement (‘R’), intensified health education (‘I’) and short-messaging services/telephonic tracing (‘Te’), abbreviated (RITe). A preintervention phase was conducted at baseline while RITe was rolled-out in the intervention phase in a sequential manner called implementation blocks: ‘I’ only—block 1; ‘I+Te’—block 2 and RITe—block 3.Main outcome measures Primary: VMMC uptake and time to VMMC for the full intervention and for each block. Secondary: predictors of VMMC uptake.Results A total of 2230 uncircumcised men presented to the STI clinic. The mean age was 29 years (SD±9), 58% were married/cohabiting, HIV prevalence was 6.4% and 43% had urethral discharge. Compared with standard of care (8/514, 1.6%), uptake increased by 100% during the intervention period (55/1716, 3.2%) (p=0.048). ‘I’ (25/731, 113%, p=0.044) and RITe (17/477, 125%, p=0.044) significantly increased VMMC uptake. The median time to VMMC was shorter during the intervention period (6 days, IQR: 0, 13) compared with standard of care (15 days, IQR: 9, 18). There was no significant incremental effect on VMMC uptake and time to VMMC between blocks. Men with genital warts were 18 times more likely to receive VMMC (adjusted relative risk=18.74, 95% CI: 2.041 to 172.453).Conclusions Our intervention addressing barriers to VMMC improved VMMC uptake and time to VMMC among uncircumcised men with STIs, an important subpopulation for VMMC prioritisation.Trial registration number NCT04677374.

Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of ADPKD are incompletely evaluated or not deemed to be clinically significant, and because of this, treatment options are limited. However, total kidney volume (TKV) measurement has become important for assessing the risk of disease progression (i.e., Mayo Imaging Classification) and predicting tolvaptan treatment’s efficacy. Deep learning for segmenting the kidneys has improved these measurements’ speed, accuracy, and reproducibility. Deep learning models can also segment other organs and tissues, extracting additional biomarkers to characterize the extent to which extrarenal manifestations complicate ADPKD. In this concept paper, we demonstrate how deep learning may be applied to measure the TKV and how it can be extended to measure additional features of this disease.

Abstract Background Perinatal depression (PND) is prevalent and negatively impacts HIV care among women living with HIV (WLHIV), yet PND remains under-identified in Malawian WLHIV. Accordingly, this formative study explored perceptions of the feasibility and acceptability of an integrated, task-shifted approach to PND screening and treatment in maternity clinics. Methods We completed consecutive PND screenings of HIV+ women attending pre- or post-natal appointments at 5 clinics in Lilongwe district, Malawi. We conducted in-depth interviews with the first 4-5 women presenting with PND per site (n = 24 total) from July to August 2018. PND classification was based on a score ≥ 10 on the Edinburgh Postnatal Depression Scale (EPDS). We conducted 10 additional in-depth interviews with HIV and mental health providers at the 5 clinics. Results Most participants endorsed the feasibility of integrated PND screening, as they believed that PND had potential for significant morbidity. Among providers, identified barriers to screening were negative staff attitudes toward additional work, inadequate staffing numbers and time constraints. Suggested solutions to barriers were health worker training, supervision, and a brief screening tool. Patient-centered counselling strategies were favored over medication by WLHIV as the acceptable treatment of choice, with providers supporting the role of medication to be restricted to severe depression. Providers identified nurses as the most suitable health workers to deliver task-shifted interventions and emphasized further training as a requirement to ensure successful task shifting. Conclusion Improving PND in a simple, task-shifted intervention is essential for supporting mental health among women with PND and HIV. Our results suggest that an effective PND intervention for this population should include a brief, streamlined PND screening questionnaire and individualized counselling for those who have PND, with supplemental support groups and depression medication readily available. These study results support the development of a PND intervention to address the gap in treatment of PND and HIV among WLHIV in Malawi.

Researchers, educators, and multimedia designers need to better understand how mixing physical tangible objects with virtual experiences affects learning and science identity. In this novel study, a 3D-printed tangible that is an accurate facsimile of the sort of expensive glassware that chemists use in real laboratories is tethered to a laptop with a digitized lesson. Interactive educational content is increasingly being placed online, it is important to understand the educational boundary conditions associated with passive haptics and 3D-printed manipulables. Cost-effective printed objects would be particularly welcome in rural and low Socio-Economic (SES) classrooms. A Mixed Reality (MR) experience was created that used a physical 3D-printed haptic burette to control a computer-based chemistry titration experiment. This randomized control trial study with 136 college students had two conditions: 1) low-embodied control (using keyboard arrows), and 2) high-embodied experimental (physically turning a valve/stopcock on the 3D-printed burette). Although both groups displayed similar significant gains on the declarative knowledge test, deeper analyses revealed nuanced Aptitude by Treatment Interactions (ATIs). These interactions favored the high-embodied experimental group that used the MR device for both titration-specific posttest knowledge questions and for science efficacy and science identity. Those students with higher prior science knowledge displayed higher titration knowledge scores after using the experimental 3D-printed haptic device. A multi-modal linguistic and gesture analysis revealed that during recall the experimental participants used the stopcock-turning gesture significantly more often, and their recalls created a significantly different Epistemic Network Analysis (ENA). ENA is a type of 2D projection of the recall data, stronger connections were seen in the high embodied group mainly centering on the key hand-turning gesture. Instructors and designers should consider the multi-modal and multi-dimensional nature of the user interface, and how the addition of another sensory-based learning signal (haptics) might differentially affect lower prior knowledge students. One hypothesis is that haptically manipulating novel devices during learning may create more cognitive load. For low prior knowledge students, it may be advantageous for them to begin learning content on a more ubiquitous interface (e.g., keyboard) before moving them to more novel, multi-modal MR devices/interfaces.

Organ volume measurements are a key metric for managing ADPKD (the most common inherited renal disease). However, measuring organ volumes is tedious and involves manually contouring organ outlines on multiple cross-sectional MRI or CT images. The automation of kidney contouring using deep learning has been proposed, as it has small errors compared to manual contouring. Here, a deployed open-source deep learning ADPKD kidney segmentation pipeline is extended to also measure liver and spleen volumes, which are also important. This 2D U-net deep learning approach was developed with radiologist labeled T2-weighted images from 215 ADPKD subjects (70% training = 151, 30% validation = 64). Additional ADPKD subjects were utilized for prospective (n = 30) and external (n = 30) validations for a total of 275 subjects. Image cropping previously optimized for kidneys was included in training but removed for the validation and inference to accommodate the liver which is closer to the image border. An effective algorithm was developed to adjudicate overlap voxels that are labeled as more than one organ. Left kidney, right kidney, liver and spleen labels had average errors of 3%, 7%, 3%, and 1%, respectively, on external validation and 5%, 6%, 5%, and 1% on prospective validation. Dice scores also showed that the deep learning model was close to the radiologist contouring, measuring 0.98, 0.96, 0.97 and 0.96 on external validation and 0.96, 0.96, 0.96 and 0.95 on prospective validation for left kidney, right kidney, liver and spleen, respectively. The time required for manual correction of deep learning segmentation errors was only 19:17 min compared to 33:04 min for manual segmentations, a 42% time saving (p = 0.004). Standard deviation of model assisted segmentations was reduced to 7, 5, 11, 5 mL for right kidney, left kidney, liver and spleen respectively from 14, 10, 55 and 14 mL for manual segmentations. Thus, deep learning reduces the radiologist time required to perform multiorgan segmentations in ADPKD and reduces measurement variability.

Summary: Background: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). Methods: This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4

Summary: Mycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and antibody development. This Mtb humoral augmentation does not occur due to cross-reactivity, a generalized increase in all antibodies, or differences in duration or amount of antigen exposure. We speculate that the co-localization of Mtb and HIV in lymphatic tissues leads to the emergence of potent HIV antibodies. PWH’s Mtb disease status has implications for the future use of HIV broadly neutralizing antibodies as prophylaxis or treatment and the induction of better humoral immunity.

Abstract Background Cryptococcal meningitis (CM) and tuberculosis (TB) remain leading causes of hospitalization and death amongst people living with HIV, particularly those with advanced HIV disease. In hospitalized patients, prompt diagnosis of these diseases may improve patient outcomes. The advanced HIV rapid diagnostic tests such as determine TB urine lipoarabinomannan lateral flow assay (urine LAM), urine X-pert MTB/RIF assay (urine X-pert), and serum/blood cryptococcal antigen test (serum CrAg) are recommended but frequently not available in many resource-limited settings. We describe our experience providing these tests in a routine hospital setting. Method From 1 August 2016 to 31 January 2017, a prospective cohort study to diagnose TB and Cryptococcal meningitis using point of care tests was conducted in the medical wards at Kamuzu Central Hospital, in Lilongwe, Malawi. The tests offered were PIMA CD4 cell count, serum CrAg, urine LAM, and urine X-pert. The testing was integrated into an existing HIV/TB treatment room on the wards and performed close to admission time. Patients were followed until discharge or death in the ward. Results We included 438 HIV-positive patients; 76% had a previously known HIV diagnosis (87% already on ART). We measured CD4 count in 365/438 (83%), serum CrAg in 301/438 (69%), urine LAM in 363/438 (83%), and urine X-pert in 292/438 (67%). The median CD4 count was 144 cells/ml (IQR 46–307). Serum CrAg positivity rate was 23 /301 (8%) and CM was confirmed by CSF Crag in 13/23 (56%). The majority of CM patients 9/13 (69%) started antifungal therapy within two days of diagnosis. Urine LAM and urine X-pert positivity rates were 81/363(22%) and (14/292 (5%) respectively. The positivity rate of urine LAM was higher in patients with low CD4 cell counts (

Abstract Background This study aimed to investigate, using Andersen’s model of health care utilization, factors associated with COVID-19 testing among adults in nine low- and middle- income countries. Methods In between 10 December 2020 and 9 February 2021, an online survey was organized in nine low- and middle-income countries. In total 10,183 adults (median age 45 years, interquartile range 33–57 years, range 18–93 years), including 6470 from Brazil, 1738 Malaysia, 1124 Thailand, 230 Bangladesh, 219 DR Congo, 159 Benin, 107 Uganda, 81 Malawi and 55 from Mali participated in the study. COVID-19 testing/infection status was assessed by self-report. Results Of the 10,183 participants, 40.3% had ever tested for COVID-19, 7.3% tested positive, and 33.0% tested negative. In an adjusted logistic regression model, predisposing factors (residing in Brazil, postgraduate education), enabling/disabling factors (urban residence, higher perceived economic status, being a student or worker in the health care sector, and moderate or severe psychological distress), and need factors (having at least one chronic condition) increased the odds of COVID-19 testing. Among those who were tested, participants residing in Bangladesh, those who had moderate to severe psychological distress were positively associated with COVID-19 positive diagnosis. Participants who are residing in Malaysia and Thailand, and those who had higher education were negatively associated with a COVID-19 positive diagnosis. Considering all participants, higher perceived economic status, being a student or worker in the health sector, and moderate or severe psychological distress were positively associated with a COVID-19 positive diagnosis, and residing in Malaysia, Thailand or five African countries was negatively associated with a COVID-19 positive diagnosis. Conclusion A high rate of COVID-19 testing among adults was reported in nine low-and middle-income countries. However, access to testing needs to be increased in Africa. Moreover, COVID-19 testing programmes need to target persons of lower economic status and education level who are less tested but most at risk for COVID-19 infection.

ABSTRACT Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log10 change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.

Multiple assessments, including a novel videogame methodology, were used to understand how viewing a Giant Screen film in four different formats affected both science identity associated with liking science and desire to be a scientist, and learning gains on STEM content. Participants were 406 5th graders who were randomly assigned to watch the 45-min film called Amazon Adventure in either a (1) 2D Small Screen, (2) 2D Giant Flat Screen, (3) 3D Giant Flat Screen, or (4) curved Dome condition. The conditions increased in levels of immersivity as listed. In this 4 × 3 design, the first factor was viewing condition and the second was test time including pretests, posttests, and two-month followup on content knowledge tests relating to natural selection. The strongest pattern was seen at the followup time point where the three more immersive conditions (2D Giant Screen, 3D Giant Screen, and Dome) outperformed the Small Screen condition on the science identity measures of liking science and wanting to be a scientist when grown up. Additionally, two of the more immersive conditions performed significantly better at both posttest and followup on the videogame that assessed natural selection and mimicry knowledge. Significant gender effects at followup revealed that females in the two most immersive conditions (3D Flat and Dome) liked science significantly more and wanted to be a scientist more than males when grown. Interestingly, females also played the videogame significantly better than the males at both posttest and followup. These results suggest that increases in the immersivity of a film can have longer term effects on science identity, and those effects are stronger in females. Additionally, as more assessments are being designed in a gamified manner, designers/researchers should keep game-style (i.e., strategy games) and gender interactions in mind. It had not been predicted that the females would outperform the males on the STEM assessment videogame, but deduction games like the one in this study are probably capturing more than knowledge about natural selection, they may be a proxies for general intelligence or g. More research is needed on game type and gender effects during the school-age developmental span.

The SARS-CoV-2 pandemic led to the rapid transition of many research studies from in-person to telephone follow-up globally. For mental health research in low-income settings, tele-follow-up raises unique safety concerns due to the potential of identifying suicide risk in participants who cannot be immediately referred to in-person care. We developed and iteratively adapted a telephone-delivered protocol designed to follow a positive suicide risk assessment (SRA) screening. We describe the development and implementation of this SRA protocol during follow-up of a cohort of adults with depression in Malawi enrolled in the Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building (SHARP) randomized control trial during the COVID-19 era. We assess protocol feasibility and performance, describe challenges and lessons learned during protocol development, and discuss how this protocol may function as a model for use in other settings. Transition from in-person to telephone SRAs was feasible and identified participants with suicidal ideation (SI). Follow-up protocol monitoring indicated a 100% resolution rate of SI in cases following the SRA during this period, indicating that this was an effective strategy for monitoring SI virtually. Over 2% of participants monitored by phone screened positive for SI in the first six months of protocol implementation. Most were passive risk (73%). There were no suicides or suicide attempts during the study period. Barriers to implementation included use of a contact person for participants without personal phones, intermittent network problems, and pre-paid phone plans delaying follow-up. Delays in follow-up due to challenges with reaching contact persons, intermittent network problems, and pre-paid phone plans should be considered in future adaptations. Future directions include validation studies for use of this protocol in its existing context. This protocol was successful at identifying suicide risk levels and providing research assistants and participants with structured follow-up and referral plans. The protocol can serve as a model for virtual SRA development and is currently being adapted for use in other contexts.

Mental illness stigma research is sparse in Malawi. Our team previously analyzed the reliability and statistical validity of a quantitative tool to measure depression-related stigma among participants with depressive symptoms using quantitative psychometric methods. This analysis aims to further evaluate the content validity of the stigma tool by comparing participants' quantitative responses with qualitative data. The SHARP project conducted depression screening and treatment at 10 noncommunicable disease clinics across Malawi from April 2019 through December 2021. Eligible participants were 18-65 years with depressive symptoms indicated by a PHQ-9 score ≥5. Questionnaires at each study timepoint included a vignette-based quantitative stigma instrument with three thematic domains: disclosure carryover (i.e., concerns about disclosure), treatment carryover (i.e., concerns about external stigma because of receiving depression treatment), and negative affect (i.e., negative attitudes about people having depression). Sub-scores were aggregated for each domain, with higher scores indicating greater stigma. To better understand participants' interpretation of this quantitative stigma questionnaire, we asked a subset of six participants a parallel set of questions in semi-structured qualitative interviews in a method similar to cognitive interviewing. Qualitative responses were linked with participants' most recent quantitative follow-up interviews using Stata 16 and NVivo software. Participants with lower quantitative stigma disclosure sub-scores had qualitative responses that indicated less stigma around disclosure, while participants with higher quantitative stigma sub-scores had qualitative responses indicating greater stigma. Similarly, in the negative affect and treatment carryover domains, participants had parallel quantitative and qualitative responses. Further, participants identified with the vignette character in their qualitative interviews, and participants spoke about the character's projected feelings and experiences based on their own lived experiences. The stigma tool was interpreted appropriately by participants, providing strong evidence for the content validity of the quantitative tool to measure these stigma domains.

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.

Depression is common among people living with HIV (PLWH). Measurement-based care models that measure depression severity and antidepressant side effects, and use an algorithm to guide antidepressant prescription by non-specialized health workers represent an evidence-based treatment for severe depression in sub-Saharan Africa. We conducted in-depth interviews from June to December 2018 with eleven patients enrolled in Project SOAR-Mental Health, a pilot project integrating depression treatment into HIV care in Malawi. Patients treated with amitriptyline or fluoxetine participated in interviews exploring antidepressant acceptability through patient knowledge, side effect severity, pill burden, adherence, perceived efficacy, and tolerability. Patients described a lack of detailed antidepressant education from their providers. Variable, typically self-limiting side effects were reported from both amitriptyline and fluoxetine. While most side effects were mild, three patients reported functional impairment. Patients reported high adherence, though the additional pill burden was a challenge. Most patients found the antidepressants efficacious, tolerable, beneficial and acceptable. Although patient psychoeducation is notably lacking as a facet of clinical management, antidepressant prescription by primary care providers appears acceptable for comorbid severe depression in PLWH initiating HIV care in sub-Saharan Africa. Health workers should be mindful of dosing to minimise side effects and considerate of the additional pill burden. Trial registration: ClinicalTrials.gov ID [NCT03555669]. Retrospectively registered on 13 June 2018.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were

BackgroundPre-exposure prophylaxis (PrEP) reduces HIV acquisition risk by >90% and is a critical lever to reduce HIV incidence. Identifying individuals most likely to benefit from PrEP and retaining them on PrEP throughout HIV risk is critical to realize PrEP’s prevention potential. Individuals with sexually transmitted infections (STIs) are an obvious priority PrEP population, but there are no data from sub-Saharan Africa (SSA) confirming the effectiveness of integrating PrEP into STI clinics. Assisted partner notification may further enhance STI clinic–based PrEP programming by recruiting PrEP users from the pool of named sexual partners of individuals presenting with an incident STI. However, the acceptability, feasibility, and effectiveness of these integrated and enhanced strategies are unknown. ObjectiveThis study aims to describe the implementation outcomes of acceptability, feasibility, and effectiveness (regarding PrEP uptake and persistence) of integrating an enhanced PrEP implementation strategy into an STI clinic in Malawi. MethodsThe enhanced PrEP STI study is a prospective cohort study enrolling patients who are eligible for PrEP (aged ≥15 years) who are seeking STI services at a Lilongwe-based STI clinic. Data collection relies on a combination of in-depth interviews, patient and clinic staff surveys, and clinic record review. All enrolled PrEP users will be screened for acute HIV infection and receive quarterly testing for Neisseria gonorrhea, Chlamydia trachomatis, and syphilis. Participants will be asked to name recent sexual partners for assisted notification; returning partners will be screened for PrEP eligibility and, if interested, enrolled into the cohort of PrEP initiators. We will also enroll patients who are eligible for PrEP but choose not to initiate it, from the STI clinic. Patient participants will be followed for 6 months; we will assess self-reported PrEP use, PrEP refills, sexual behaviors, perceived HIV risk, and incident STIs. Clinic staff participants will be interviewed at baseline and at approximately 6 months and will complete surveys examining the perceived acceptability and feasibility of the integrated and enhanced PrEP strategy. ResultsEnrollment began in March 2022 and is projected to continue until February 2023, with patient participant follow-up through August 2023. The results of this study are expected to be reported in 2024. ConclusionsThis study will generate important evidence regarding the potential integration of PrEP services into STI clinics in SSA and preliminary data regarding the effectiveness of an enhanced intervention that includes assisted partner notification as a strategy to identify potential PrEP users. Furthermore, this trial will provide some of the first insights into STI incidence among PrEP users recruited from an STI clinic in SSA—critical data to inform the use of etiologic STI testing where syndromic management is the current standard. These findings will help to design future PrEP implementation strategies in SSA. Trial RegistrationClinicalTrials.gov NCT05307991; https://clinicaltrials.gov/ct2/show/NCT05307991 International Registered Report Identifier (IRRID)DERR1-10.2196/37395

Summary: Background: The identification of baseline host determinants that associate with robust HIV-1 vaccine-induced immune responses could aid HIV-1 vaccine development. We aimed to assess both the collective and relative performance of baseline characteristics in classifying individual participants in nine different Phase 1-2 HIV-1 vaccine clinical trials (26 vaccine regimens, conducted in Africa and in the Americas) as High HIV-1 vaccine responders. Methods: This was a meta-analysis of individual participant data, with studies chosen based on participant-level (vs. study-level summary) data availability within the HIV-1 Vaccine Trials Network. We assessed the performance of 25 baseline characteristics (demographics, safety haematological measurements, vital signs, assay background measurements) and estimated the relative importance of each characteristic in classifying 831 participants as High (defined as within the top 25th percentile among positive responders or above the assay upper limit of quantification) versus Non-High responders. Immune response outcomes included HIV-1-specific serum IgG binding antibodies and Env-specific CD4+ T-cell responses assessed two weeks post-last dose, all measured at central HVTN laboratories. Three variable importance approaches based on SuperLearner ensemble machine learning were considered. Findings: Overall, 30.1%, 50.5%, 36.2%, and 13.9% of participants were categorized as High responders for gp120 IgG, gp140 IgG, gp41 IgG, and Env-specific CD4+ T-cell vaccine-induced responses, respectively. When including all baseline characteristics, moderate performance was achieved for the classification of High responder status for the binding antibody responses, with cross-validated areas under the ROC curve (CV-AUC) of 0.72 (95% CI: 0.68, 0.76) for gp120 IgG, 0.73 (0.69, 0.76) for gp140 IgG, and 0.67 (95% CI: 0.63, 0.72) for gp41 IgG. In contrast, the collection of all baseline characteristics yielded little improvement over chance for predicting High Env-specific CD4+ T-cell responses [CV-AUC: 0.53 (0.48, 0.58)]. While estimated variable importance patterns differed across the three approaches, female sex assigned at birth, lower height, and higher total white blood cell count emerged as significant predictors of High responder status across multiple immune response outcomes using Approach 1. Of these three baseline variables, total white blood cell count ranked highly across all three approaches for predicting vaccine-induced gp41 and gp140 High responder status. Interpretation: The identified features should be studied further in pursuit of intervention strategies to improve vaccine responses and may be adjusted for in analyses of immune response data to enhance statistical power. Funding: National Institute of Allergy and Infectious Diseases (UM1AI068635 to YH, UM1AI068614 to GDT, UM1AI068618 to MJM, and UM1 AI069511 to MCK), the Duke CFAR P30 AI064518 to GDT, and National Institute of Dental and Craniofacial Research (R01DE027245 to JJK). This work was also supported by the Bill and Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding sources.

Abstract Background Integration of depression services into infectious disease care is feasible, acceptable, and effective in sub-Saharan African settings. However, while the region shifts focus to include chronic diseases, additional information is required to integrate depression services into chronic disease settings. We assessed service providers’ views on the concept of integrating depression care into non-communicable diseases’ (NCD) clinics in Malawi. The aim of this analysis was to better understand barriers, facilitators, and solutions to integrating depression into NCD services. Methods Between June and August 2018, we conducted nineteen in-depth interviews with providers. Providers were recruited from 10 public hospitals located within the central region of Malawi (i.e., 2 per clinic, with the exception of one clinic where only one provider was interviewed because of scheduling challenges). Using a semi structured interview guide, we asked participants questions related to their understanding of depression and its management at their clinic. We used thematic analysis allowing for both inductive and deductive approach. Themes that emerged related to facilitators, barriers and suggested solutions to integrate depression assessment and care into NCD clinics. We used CFIR constructs to categorize the facilitators and barriers. Results Almost all providers knew what depression is and its associated signs and symptoms. Almost all facilities had an NCD-dedicated room and reported that integrating depression into NCD care was feasible. Facilitators of service integration included readiness to integrate services by the NCD providers, availability of antidepressants at the clinic. Barriers to service integration included limited knowledge and lack of training regarding depression care, inadequacy of both human and material resources, high workload experienced by the providers and lack of physical space for some depression services especially counseling. Suggested solutions were training of NCD staff on depression assessment and care, engaging hospital leaders to create an NCD and depression care integration policy, integrating depression information into existing documents, increasing staff, and reorganizing clinic flow. Conclusion Findings of this study suggest a need for innovative implementation science solutions such as reorganizing clinic flow to increase the quality and duration of the patient-provider interaction, as well as ongoing trainings and supervisions to increase clinical knowledge. Trial registration This study reports finding of part of the formative phase of “The Sub-Saharan Africa Regional Partnership (SHARP) for Mental Health Capacity Building—A Clinic-Randomized Trial of Strategies to Integrate Depression Care in Malawi” registered as NCT03711786

Abstract Background The prevalence of Human Immunodeficiency Virus (HIV) among prisoners remains high in many countries, especially in Africa, despite a global decrease in HIV incidence. Programs to reach incarcerated populations with HIV services have been implemented in Malawi, but the success of these initiatives is uncertain. We explored which challenges prisoners face in receiving essential HIV services and whether HIV risk behavior is prevalent in prisons. Methods We conducted a mixed-methods (qualitative and quantitative), cross-sectional study in 2018 in six prisons in Southern Malawi, two large central prisons with on-site, non-governmental organization (NGO) supported clinics and 4 smaller rural prisons. Four hundred twelve prisoners were randomly selected and completed a structured questionnaire. We conducted in-depth interviews with 39 prisoners living with HIV, which we recorded, transcribed and translated. We used descriptive statistics and logistic regression to analyze quantitative data and content analysis for qualitative data. Results The majority of prisoners (93.2%) were male, 61.4% were married and 63.1% were incarcerated for 1–5 years. Comprehensive services were reported to be available in the two large, urban prisons. Female prisoners reported having less access to general medical services than males. HIV risk behavior was reported infrequently and was associated with incarceration in urban prisons (adjusted odds ratio [aOR] 18.43; 95% confidence interval [95%-CI] 7.59–44.74; p =

# Background Timely diagnosis of HIV in infants and children is an urgent priority. In Malawi, 40,000 infants annually are HIV exposed. However, gold standard polymerase-chain-reaction (PCR) based testing requires centralised laboratories, causing turn-around times (TAT) of 2 to 3 months and significant loss to follow-up. If feasible and acceptable, minimising diagnostic delays through HIV Point-of-care-testing (POCT) may be cost-effective. We assessed whether POCT Cepheid Xpert HIV-1 Qual assay whole blood (XpertHIV) was more cost-effective than PCR. # Methods From July-August 2018, 700 PCR Abbott tests using dried blood spots (DBS) were performed on 680 participants who enrolled on the feasibility, acceptability and performance of the XpertHIV study. Newly identified HIV-positive DBS from the 680 participants were retested, so with confirmatory testing of the HIV-positive cases, 700 tests were performed. We conducted a cost-minimisation and cost-effectiveness analysis of XpertHIV against PCR, as the standard of care. A random sample of 200 caregivers from the 680 participants had semi-structured interviews to explore costs from a societal perspective of XpertHIV at Mulanje District Hospital, Malawi. Analysis used TAT as the primary outcome measure. Results were extrapolated from the study period (29 days) to a year (240 working days). Sensitivity analyses characterised individual and joint parameter uncertainty and estimated patient cost per test. # Results During the study period, XpertHIV was cost-minimising at \$42.34 per test compared to \$66.66 for PCR. Over a year, XpertHIV remained cost-minimising at \$16.12 compared to PCR at \$27.06. From the patient perspective (travel, food, lost productivity), the cost per test of XpertHIV was \$2.45. XpertHIV had a mean TAT of 7.10 hours compared to 153.15 hours for PCR. Extrapolates accounting for equipment costs, lab consumables and losses to follow up estimated annual savings of \$2,193,538.88 if XpertHIV is used nationally, as opposed to PCR. # Conclusions This preliminary evidence suggests that adopting POCT XpertHIV will save time, allowing HIV-exposed infants to receive prompt care and may improve outcomes. The Malawi government will pay less due to XpertHIV's cost savings and associated benefits.

Abstract The Malawi College of Medicine and its partners are building non-communicable diseases’ (NCDs’) research capacity through a grant from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. Several strategies are being implemented including research mentorship for junior researchers interested to build careers in NCDs’ research. In this article, we present the rationale for and our experiences with this mentorship program over its 2 years of implementation. Lessons learned and the challenges are also shared.

Atrial fibrillation is the most common arrhythmia in clinical practice with indication for anticoagulation in those patients whose annual risk for thromboembolism is >2%. Left atrial appendage closure is growing as an alternative to anticoagulation. We present a case of pulmonary artery-left atrial appendage fistula seen after left atrial appendage closure. (Level of Difficulty: Intermediate.)

Objectives: To investigate psychosocial factors associated with adherence to COVID-19 preventive measures in low- and middle-income countries (LMICs).Methods: This online cross-sectional survey included 10,183 adults (median age 45 years) from nine LMICs. Participants were asked about adhering to four COVID-19 preventive measures (physical distancing, wearing a face mask, hand, and cough hygiene); a composite adherence score was calculated, ranging from 0–4 positive responses. Psychosocial measures included worry, anxiety, depression, social and demographic, and COVID-19 related factors.Results: Factors associated with adherence to more preventive measures included being a participant from Malaysia or Bangladesh, older age, higher education, belonging to the healthcare sector (either as or worker), having health personnel as a trusted source of COVID-19 information/advice, possessing correct COVID-19 knowledge, worry or fear about being (re)infected with COVID-19, and screening negative for general anxiety symptoms.Conclusion: Moderate to high adherence to COVID-19 preventive measures was found, with significant variations across countries. Psychosocial factors (worry, anxiety, knowledge, education, age, and country) seemed determinant in predicting the number of measures to which participants adhered.

Background Viral load (VL) testing coverage remains low particularly in resource limited countries despite recommendation by World Health Organization, and Malawi is no exception. A quality improvement (QI) approach was used to improve VL testing coverage from 27% to a target of 80% at an urban health facility in Malawi. Methods A QI study employing a time-series quasi-experimental design with no comparison group was conducted at Chilomoni health centre in Blantyre from April 2020 to July 2020. A retrospective record review of all patient records (257) from 8 weeks before the study was conducted to determine baseline VL testing coverage. Root cause analysis of low VL testing coverage was done using fish-bone tool and factors prioritized using a Pareto-chart. Priority factors included inadequate capacity to update electronic medical records and competing tasks. Change ideas were identified and prioritized using an effort-impact matrix. Two change ideas; re-orienting ART providers on VL test order in EMR and dedicated ART provider to serve VL tested patients were implemented and tested in 5 Plan-Do-Study-Act (PDSA) cycles from the Model for Improvement (MFI), each lasting one week. The latter was tested, and adapted in 3 cycles, and eventually adopted for monitoring for another 5 weeks. VL testing coverage was tracked throughout the study using run charts and p-charts. Results VL testing coverage increased from 27% to 71% by the end of the study, with children aged 0 to 14 years having the lowest coverage throughout the study. Conclusion The MFI as a QI approach improved VL testing coverage through implementation of contextualized change ideas. A reliable data system, leadership buy-in and commitment are important for sustained improvement. Future research should focus on evaluating sustainability of improved VL testing coverage at the health facility and assessing barriers to VL testing among the paediatric population.

Background Couples HIV Counselling and Testing (CHCT) has been found to be potentially beneficial than individual HIV Counselling and Testing for prevention and treatment of HIV. However, there are few health care opportunities for men and women to access health services together, leading to underutilization of CHCT service. Integrating female Sexual and Reproductive Health (SRH) services into male-dominated service could be more effective than trying to integrate men’s health services into female-dominated health services. A potential site for male-female service integration could be Voluntary Medical Male Circumcision (VMMC) centers. Methodology We conducted a qualitative study in Lilongwe, Malawi between June to August 2018. Twenty VMMC clients, 20 peers and 20 VMMC providers completed individual in-depth interviews to share their opinions on what they thought about integrating CHCT and other SRH Services into VMMC services. These proposed SRH services include family planning, cervical cancer screening, sexually transmitted infection management and pre-exposure prophylaxis (PrEP). Content analysis was used to analyze the results. Results All participants were receptive to integration of CHCT, and most accepted the integration of SRH services into VMMC Services. Most VMMC clients, peers and care providers said that CHCT integration would help couples to know their HIV status, prevent HIV transmission, encourage healthy relationships, and provide a chance for women to participate in VMMC counselling and wound care. However, integration of other services, such as family planning and cervical cancer screening, drew mixed opinions among participants. Most VMMC clients, peers and providers felt that integration of services would promote male involvement and increase men’s knowledge in feminine sexual reproductive health services. A few providers expressed concerns over service integration, citing reasons such as overcrowding, work overload, gender mixing, and lack of provider capacity and space. Most participants supported integrating PrEP with VMMC Services and felt that PrEP would complement VMMC in HIV prevention. Few providers, peers and VMMC clients felt the addition of PrEP to VMMC services would lead to high-risk sexual activity that would then increase the risk for HIV acquisition. A few participants recommended community sensitization when integrating some of sexual reproductive health services into VMMC Services to mitigate negative perceptions about VMMC services and encourage service uptake among couples Conclusion Most participants service providers, VMMC clients and Peers were receptive to integrating SRH services, particularly HIV prevention services such as CHCT and PrEP, into male dominated VMMC services. Adequate community sensitization is required when introducing other SRH services into VMMC services.

Introduction Long-term care engagement of women on antiretroviral therapy (ART) is essential to effective HIV public health measures. We sought to explore factors associated with a history of HIV treatment interruption among pregnant women living with HIV presenting to an antenatal clinic in Lilongwe, Malawi. Methods We performed a cross-sectional study of pregnant women living with HIV who had a history of ART interruption presenting for antenatal care. Women were categorized as either retained in HIV treatment or reinitiating care after loss-to-follow up (LTFU). To understand factors associated with treatment interruption, we surveyed socio-demographic and partner relationship characteristics. Crude and adjusted prevalence ratios (aPR) for factors associated with ART interruption were estimated using modified Poisson regression with robust variance. We additionally present patients’ reasons for ART interruption. Results We enrolled 541 pregnant women living with HIV (391 retained and 150 reinitiating). The median age was 30 years (interquartile range (IQR): 25–34). Factors associated with a history of LTFU were age Conclusions Interventions that simplify the ART clinic transfer process, facilitate partner disclosure, and provide counseling about the importance of lifelong ART beyond pregnancy and breastfeeding should be further evaluated for improving retention in ART treatment of women living with HIV in Malawi.

Introduction Voluntary medical male circumcision (VMMC) is one of the key interventions for HIV prevention. However, its uptake among men in Malawi is low. Implementation science strategies for demand creation of VMMC increase uptake. We designed an implementation science demand-creation intervention to increase the uptake of VMMC among men with sexually transmitted infections (STIs).Methods and analysis We designed a pragmatic pre-interventional and post-interventional quasi-experimental study combined with a prospective observational design to determine the uptake, acceptability, appropriateness and feasibility of a multifaceted intervention for scale up of uptake of VMMC among men with STIs at Bwaila STI clinic in Lilongwe, Malawi. The intervention includes transport reimbursement (R), intensified health education (I) and short messaging service (SMS)/telephonic tracing (Te) (RITe). The intervention will be implemented in phases: pre-implementation and implementation. Pre-implementation phase will be used for collecting baseline data, while the RITe intervention will be rolled-out in the implementation phase. The RITe intervention will be implemented in a sequential and incremental manner called implementation blocks: block 1: intensified health education; block 2: intensified health education and SMS/telephonic tracing; and block 3: intensified health education, SMS/telephonic tracing and transport reimbursement. The target sample size is 80 uncircumcised men for each intervention block, including the pre-implementation sample, making a total of 320 men (280 total, 70 per block will be surveyed). The primary outcome is uptake of VMMC during the implementation period. Mixed methods assessments will be conducted to evaluate the acceptability, appropriateness and feasibility of the RITe intervention.Ethics and dissemination The study protocol was approved by the Malawi’s National Health Sciences Research Ethics Committee (approval number: 19/10/2412), University of North Carolina at Chapel Hill’s Institutional Review Board (approval number: 19–2559) and University of the Witwatersrand’s Health Research Ethics Committee (approval number: M200328). Results will be disseminated via publication in a peer-reviewed journal and presentations at relevant scientific conferences and meetings.Trial registration number NCT04677374.