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.

Enhancing SARS-CoV-2 surveillance in Malawi using telephone syndromic surveillance from July 2020 to April 2022.

INTRODUCTION: Monitoring the SARS-CoV-2 pandemic in low-resource countries such as Malawi requires cost-effective surveillance strategies. This study explored the potential utility of phone-based syndromic surveillance in terms of its reach, monitoring trends in reported SARS-CoV-2-like/influenza-like symptoms (CLS/ILS), SARS-CoV-2 testing and mortality. METHODS: Mobile phone-based interviews were conducted between 1 July 2020 and 30 April 2022, using a structured questionnaire. Randomly digital dialled numbers were used to reach individuals aged ≥18 years who spoke Chichewa or English. Verbal consent was obtained, and trained research assistants with clinical and nursing backgrounds collected information on age, sex, region of residence, reported CLS/ILS in the preceding 2 weeks, SARS-CoV-2 testing and history of household illness and death. Data were captured on tablets using the Open Data Kit database. We performed a descriptive analysis and presented the frequencies and proportions with graphical representations over time. FINDINGS: Among 356 525 active phone numbers, 138 751 (38.9%) answered calls, of which 104 360 (75.2%) were eligible, 101 617 (97.4%) consented to participate, and 100 160 (98.6%) completed the interview. Most survey respondents were aged 25-54 years (72.7%) and male (65.1%). The regional distribution of the respondents mirrored the regional population distribution, with 45% (44%) in the southern region, 41% (43%) in the central region and 14% (13%) in the northern region. The reported SARS-CoV2 positivity rate was 11.5% (107/934). Of the 7298 patients who reported CLS/ILS, 934 (12.8%) reported having undergone COVID-19 testing. Of the reported household deaths, 47.2% (982 individuals) experienced CLS/ILS 2 weeks before their death. CONCLUSION: Telephonic surveillance indicated that the number of SARS-CoV-2 cases was at least twice as high as the number of confirmed cases in Malawi. Our findings also suggest a substantial under-reporting of SARS-CoV-2-related deaths. Telephonic surveillance has proven feasible in Malawi, achieving the ability to characterise SARS-CoV-2 morbidity and mortality trends in low-resource settings.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). INTERPRETATION: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

Early Effects of Scaling Up Dolutegravir-Based ARV Regimens Among Children Living with HIV in Malawi.

Viral suppression (VS) in children has remained suboptimal compared to that in adults. We evaluated the impact of transitioning children weighing < 20 kg to a pediatric formulation of dolutegravir (pDTG) on VS in Malawi. We analyzed routine retrospective program data from electronic medical record systems pooled across 169 healthcare facilities in Malawi supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). We included children who weighed < 20 kg and received antiretroviral therapy (ART) between July 2021-June 2022. Using descriptive statistics, we summarized demographic and clinical characteristics, ART regimens, ART adherence, and VS. We used logistic regression to identify factors associated with post-transition VS. A total of 2468 Children Living with HIV (CLHIV) were included, 55.3% of whom were < 60 months old. Most (83.8%) had initiated on non-DTG-based ART; 71.0% of these had a viral load (VL) test result before transitioning to pDTG, and 62.5% had VS. Nearly all (99.9%) CLHIV transitioned to pDTG-based regimens. Six months after the transition, 52.7% had good ART adherence, and 38.6% had routine VL testing results; 81.7% achieved VS. Post-transition VS was associated with good adherence and pre-transition VS: adjusted odds ratios of 2.79 (95% CI 1.65-4.71), p < 0.001 and 5.32 (95% CI 3.23-9.48), p < 0.001, respectively. After transitioning to pDTG, VS was achieved in most children tested within the first 6 months. However, adherence remained suboptimal post-transition and VL testing at 6 months was limited. Interventions to improve VL testing and enhance ART adherence are still needed in CLHIV on pDTG-based regimens.

HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa.

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

Understanding health systems challenges in providing Advanced HIV Disease (AHD) care in a hub and spoke model: a qualitative analysis to improve AHD care program in Malawi.

BACKGROUND: Despite tremendous progress in antiretroviral therapy (ART) and access to ART, many patients have advanced human immunodeficiency virus (HIV) disease (AHD). Patients on AHD, whether initiating ART or providing care after disengagement, have an increased risk of morbidity and mortality. The Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) launched an enhanced care package using a hub-and-spoke model to optimize AHD care in Malawi. This model improves supply availability and appropriate linkage to care. We utilized a hub-and-spoke model to share health facility challenges and recommendations on the AHD package for screening and diagnosis, prophylaxis, treatment, and adherence support. METHODS: This qualitative study assessed the facility-level experiences of healthcare workers (HCWs) and lay cadres (LCs) providing AHD services to patients through an intervention package. The study population included HCWs and LCs supporting HIV care at four intervention sites. Eligible study participants were recruited by trained Research Assistants with support from the health facility nurse to identify those most involved in supporting patients with AHD. A total of 32 in-depth interviews were conducted. Thematic content analysis identified recurrent themes and patterns across participants' responses. RESULTS: While HCWs and LCs stated that most medications are often available at both hub and spoke sites, they reported that there are sometimes limited supplies and equipment to run samples and tests necessary to provide AHD care. More than half of the HCWs stated that AHD training sufficiently prepared them to handle AHD patients at both the hub and spoke levels. HCWs and LCs reported weaknesses in the patient referral system within the hub-and-spoke model in providing a linkage of care to facilities, specifically improper referral documentation, incorrect labeling of samples, and inconsistent availability of transportation. While HCWs felt that AHD registers were time-consuming, they remained motivated as they thought they provided better patient services. CONCLUSIONS: These findings highlight the importance of offering comprehensive AHD services. The enhanced AHD program addressed weaknesses in service delivery through decentralization and provided services through a hub-and-spoke model, improved supply availability, and strengthened linkage to care. Additionally, addressing the recommendations of service providers and patients is essential to improve the health and survival of patients with AHD.

Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data.

BACKGROUND: In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi. METHODS: We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021. RESULTS: In surveys, 11.0% (95% confidence interval, 10.7%-11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%-55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%-6.1%) for genital ulcer, 3.8% (2.0%-6.7%) for vaginal discharge, and 2.6% (1.2%-4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi. CONCLUSIONS: Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.

'ARVs are a constant reminder of lost freedom, whereas for others, they are liberating': understanding the treatment narrative among people living with HIV (PLHIV) in Malawi and Zimbabwe-a qualitative study.

OBJECTIVE: The aim of the research was to understand what drives and motivates young women living with HIV in their treatment journeys, as well as their key influencers. The findings will assist in appreciating their obstacles to treatment and constructing the most effective ways to convey fresh messages to them. These insights will contribute to the messaging developed for a campaign across sub-Saharan Africa, primarily Malawi and Zimbabwe. DESIGN: This was a qualitative study conducted in order to build an understanding of unknown parts of the HIV treatment journey through in-depth interviews. A hybrid approach was used to conduct thematic analysis. SETTING AND PARTICIPANTS: Study participants were HIV-positive women, their influencers (eg, parents/partners/siblings/aunts and uncles/religious leaders, etc) and healthcare providers from a range of regions in Zimbabwe and Malawi. RESULTS: A total of 26 young people living with HIV (PLHIV), 29 healthcare providers and 24 influencers such as maternal figures in the community were interviewed. Two main broad insights were drawn, that is, key needs and wider contextual factors. The key needs of young PLHIV to stay on treatment were empathy, support and emotional connection with antiretroviral therapy (ART), while the wider contextual factors impacting their treatment journeys were structural challenges and cultural reference points. Fear of shame and humiliation can also be significant barriers to disclosure and treatment. The fear predisposes the PLHIV to the need for empathy, support and connection with ART. Mental health and anxiety appear to be comorbid with HIV. Some PLHIV have a small and limited support network leading to very few people living openly with HIV. There is no 'one-size-fits-all' approach, and maximising campaign reach will likely need a multifaceted approach. CONCLUSION: Currently, the relationship between nurses and PLHIV can appear to be transactional. Through learning about the community (including PLHIV), there are more chances of communicating in a way that resonates.

Understanding gender differences of people with HIV newly diagnosed or returning to care with advanced HIV disease in Malawi: a qualitative study.

BACKGROUND: Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi. METHODS: We used a qualitative study design, interviewing 16 men and 16 women aged 18 years and above diagnosed with AHD in sites implementing an optimized package of AHD care, from December 2021-February 2022. We included study participants receiving AHD services for at least two months. We also interviewed 16 lay workers and 16 health care workers supporting people living with AHD. In-depths interviews (IDIs) were conducted in English or Chichewa by trained research assistants using semi-structured interview guides. A short-answer analysis was conducted, and findings were interpreted according to thematic areas. RESULTS: Both men and women reported stigma as a main barrier influencing their decision to test for HIV and to initiate and adhere to ART. Fear of side effects, insufficient food, and the need for more information were other barriers reported among men and women as well as perceived as barriers by HCWs. Men appear to have tested later for HIV and stated that they were waiting until experiencing significant symptoms before testing. According to clients and HCWs, men were also less inclined to initiate ART after a HIV diagnosis, whereas women were motivated to start treatment to remain healthy and care for the family. Both genders reported that treatment could be delayed if they were feeling healthy. Treatment fatigue was reported among all groups as the main reason to discontinue treatment. CONCLUSIONS: There were similarities and differences between genders in decision-making about HIV care. Concerns about stigma were important reasons for delay in HIV care in both genders. Motivations for accessing HIV treatment and care were different among men and women, pushing the need for gender-tailored counseling services and community messaging that educate both men and women on the benefits of initiating ART early, in turn reducing the number of people presenting with AHD. TRIAL REGISTRATION: NCT05510973, first registration 22/08/2022.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.