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.

Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi.

BACKGROUND: The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi. METHODS: Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%. RESULTS: The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25-49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23-42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15-24 years, individuals aged 25-49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35-0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20-0.58), indicating a 67% decreased likelihood compared to the youngest age group 15-24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation. CONCLUSION: This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15-24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens.

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.

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.

Influence of the SARS-COV2 pandemic on access to healthcare services among people living with HIV and its subsequent effects on antiretroviral therapy uptake in Malawi.

The global disruption caused by the SARS-CoV-2 pandemic profoundly affected healthcare systems, particularly impacting People Living with Human Immunodeficiency Virus (PLHIV). This study investigated the repercussions of SARS-CoV-2 infection on access to human immunodeficiency virus (HIV) care and antiretroviral therapy (ARV) in Malawi, emphasizing the critical need to sustain uninterrupted HIV services during health crises. Employing mobile phone-based syndromic surveillance, this study assessed the influence of SARS-CoV-2 on healthcare access for PLHIV across nine districts supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). Telephone-based interviews were conducted to analyze demographic factors, challenges encountered in accessing HIV services, and adherence to ARV medication, illuminating the pandemic's effects on ARV uptake. The findings revealed that approximately 3.9% (n = 852) of 21981 participants faced obstacles in accessing crucial HIV services during the pandemic, resulting in approximately 1.2% (n = 270) reporting multiple missed doses of ARV medication in a particular month. After adjusting for various variables, males exhibited a higher likelihood of service inaccessibility than females (Adjusted Odds Ratio [AOR] = 1.39, 95% CI: 1.20-1.60, p < 0.001). Age also played a significant role, with individuals aged 35-49 years and those aged 50 years or older demonstrating reduced odds of service failure compared with the reference group aged 18-34 years. Only a small proportion of PLHIV reported disruption in HIV care access, which may be because Malawi did not initiate stringent travel restrictions during the SARS-CoV-2 pandemic. Nonetheless, enduring challenges have been observed in retaining younger PLHIV and men in HIV-care settings. Thus, targeted strategies are imperative for effectively engaging and sustaining these populations in HIV care during and after health crises.

Cost of Providing Advanced HIV Disease Treatment Services through Malawi's Hub-and-Spoke Model.

Antimicrobial prophylaxis and treatment of opportunistic infections immediately before or at the start of antiretroviral therapy (ART) improves prognosis and decreases death rates among patients with advanced HIV disease (AHD). In this study, we estimated the average cost per patient receiving AHD services (PP) and per client retained (PR) at 12 months. The study population included children, adolescents, and adults enrolled in the AHD program at 13 hub and 19 spoke sites in Malawi. To evaluate the cost PP and PR, we divided the cost of providing AHD services at 12 months by the total number of patients who received these services and who were retained in AHD services care at 12 months, respectively. We enrolled 246 AHD patients, with 137 retained at 12 months. The cost of providing AHD services to 246 patients at 12 months was $59,063; cost PP was $240, and cost PR was $431. Drugs were the largest expenditure (30%), followed by travel for supportive supervision (24%), clinic visit costs (19%), site support personnel (8%), laboratory tests (7%), annualized training costs (6%), consumables (3%), and meetings (3%). The cost of ART was $11,754; however, ART would be provided regardless of whether the AHD package was in place. Any reduction in overall costs of AHD care will require coordination among procurement partners and negotiations with manufacturers to help reduce the prices of drugs and laboratory consumables. This calls for further improvement of efficiency and capacity of site-level staff to reduce costs related to supportive supervision.

Factors associated with COVID-19 vaccine receipt among mobile phone users in Malawi: Findings from a national mobile-based syndromic surveillance survey, July 2021-April 2022.

Malawi recommended COVID-19 vaccines for adults aged ≥18 years in March 2021. We assessed factors associated with receiving COVID-19 vaccines in Malawi as part of a telephone-based syndromic surveillance survey. We conducted telephone-based syndromic surveillance surveys with questions on COVID-19 vaccine receipt among adults (≥18 years old) upon verbal consent from July 2021 to April 2022. We used random digit dialing to select mobile phone numbers and employed electronic data collection forms on secure tablets. Survey questions included whether the respondent had received at least one dose of a COVID-19 vaccine. We used multivariable analysis to identify factors associated with COVID-19 vaccine receipt. Of the 51,577 participants enrolled; 65.7% were male. Males were less likely to receive the COVID-19 vaccine than females (AOR 0.83, 95% CI 0.80-0.86). Compared to those aged 18-24 years, older age had increased odds of vaccine receipt: 25-34 years (AOR 1.32, 95% CI 1.24-1.40), 35-44 years (AOR 2.00, 95% CI 1.88-2.13), 45-54 years (AOR 3.02, 95% CI 2.82-3.24), 55-64 years (AOR 3.24, 95% CI 2.93-3.57) and 65 years+ (AOR 3.98, 95% CI 3.52-4.49). Respondents without formal education were less likely to receive vaccination compared to those with primary (AOR 1.30, 95% CI 1.14-1.48), secondary (AOR 1.76, 95% CI 1.55-2.01), and tertiary (AOR 3.37, 95% CI 2.95-3.86) education. Respondents who thought COVID-19 vaccines were unsafe were less likely to receive vaccination than those who thought it was very safe (AOR 0.26, 95% CI 0.25-0.28). Residents of the Central and Southern regions had reduced odds of vaccine receipt compared to those in the North (AORs 0.79, (95% CI 0.74-0.84) and 0.55, (95% CI 0.52-0.58) respectively). Radio (72.6%), health facilities (52.1%), and social media (16.0%) were the more common self-reported sources of COVID-19 vaccine information. COVID-19 vaccine receipt is associated with gender, age, education, and residence. It is important to consider these factors when implementing COVID-19 vaccination programs.

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.

Acceptability and usability of a paediatric HIV screening tool in high-volume outpatient settings in Malawi, perspectives from caregivers and healthcare workers.

BACKGROUND: Using an HIV pretest screening tool to identify children most at risk for HIV infection may be a more efficient and cost-effective approach to identify children living with HIV in resource-limited settings. These tools seek to reduce overtesting of children by increasing the positive predictive value while ensuring a high negative predictive value for those screened for HIV. METHODS: This qualitative study in Malawi evaluated acceptability and usability of a modified version of the Zimbabwe HIV screening tool to identify children aged 2-14 years most-at-risk. The tool included additional questions about previous hospitalisations due to malaria and prior documented diagnoses. Sixteen interviews were conducted with expert clients (ECs), trained peer-supporters, which administered the screening tool and 12 interviews with biological and non-biological caregivers of screened children. All interviews were audiorecorded, transcribed and translated. Transcripts were analysed manually using a short-answer analysis, compiling responses for each question by study participant group. Summary documents were generated, identifying common and outlier perspectives. RESULTS: The HIV paediatric screening tool was generally accepted by caregivers and ECs, with both groups seeing the benefit of the tool and promoting its use. The ECs who were primarily responsible for implementing the tool initially struggled with acceptance of the tool but started to accept it after additional training and mentorship was provided. Overall, caregivers accepted having their children tested for HIV, although non-biological caregivers expressed hesitancy in giving consent for HIV testing. ECs reported challenges with the ability for non-biological caregivers to answer some questions. CONCLUSION: This study found general acceptance of paediatric screening tools in children in Malawi and identified some minor challenges that raise important considerations for tool implementation. These include the need for a thorough orientation of the tools for the healthcare workers and caregivers, appropriate space at the facility, and adequate staffing and commodities.

Safety of Janssen Ad26.COV.S and Astra Zeneca AZD1222 COVID-19 Vaccines among Mobile Phone Users in Malawi: Findings from a National Mobile-Based Syndromic Surveillance Survey, July 2021 to December 2021.

The safety profiles of the Ad26.COV2.S and AZD1222 COVID-19 vaccines have not been described in the general population in Malawi. We present self-reported adverse events (AE) following the receipt of these vaccines in Malawi as part of a national syndromic surveillance survey. We conducted phone-based syndromic surveillance surveys among adults (≥18 years) with verbal consent. We used secure tablets through random digit dialing to select mobile phone numbers and collected data electronically. Survey questions included whether the respondent had received the COVID-19 vaccines, whether they had experienced any AE following vaccination, and the severity of the AE. We used multivariable analysis to identify factors associated with self-reported AE post-COVID-19 vaccination. A total of 11,924 (36.0%) out of 33,150 respondents reported receiving at least one dose of either Ad26.COV2.S or AZD1222 between July-December 2021; of those, 65.1% were female. About 49.2% of the vaccine recipients reported at least one AE, 90.6% of which were mild, and 2.6% were severe. Higher education level and concern about the safety of COVID-19 vaccines were associated with AE self-report (Adjusted Odds Ratio [AOR] 2.63 [95% CI 1.96-3.53] and 1.44, [95% CI 1.30-1.61], respectively), while male gender and older age were associated with reduced likelihood of AE self-report (AORs 0.81, [95% CI 0.75-0.88], 0.62 [95% CI 0.50-0.77], respectively). Ad26.COV2.S and AZD1222 vaccines are well-tolerated, with primarily mild and few severe AE among adults living in Malawi. Self-reporting of AE following COVID-19 vaccination is associated with gender, age, education, and concern about the safety of the vaccines. Recognizing these associations is key when designing and implementing COVID-19 vaccination communication messages to increase vaccination coverage.

Protocol to implement a syndromic surveillance survey of COVID-19 in Malawi.

Introduction: Malawi experienced two waves of COVID-19 between April 2020 and February 2021. A High negative impact of COVID-19 was experienced in the second wave, with increased hospital admissions that overwhelmed the healthcare system. This paper describes a protocol to implement a telephone-based syndromic surveillance system to assist public health leaders in the guidance, implementation, and evaluation of programs and policies for COVID-19 prevention and control in Malawi. Study design: This is a serial cross-sectional telephonic-based national survey focusing on the general population and People living with HIV and AIDS. Methods: We will conduct a serial cross-sectional telephone survey to assess self-reported recent and current experience of influenza-like illness (ILI)/COVID-19-like-illness (CLI), household deaths, access to routine health services, and knowledge related to COVID-19. Structured questionnaires will be administered to two populations: 1) the general population and 2) people living with HIV (PLHIV) on antiretroviral therapy (ART) at EGPAF-supported health facilities. Electronic data collection forms using secure tablets will be used based on randomly selected mobile numbers from electronic medical records (EMR) for PLHIV. We will use random digit dialing (RDD) for the general population to generate phone numbers to dial respondents. The technique uses computer-generated random numbers, using the 10-digit basic structure of mobile phone numbers for the two existing mobile phone companies in Malawi. Interviews will be conducted only with respondents that will verbally consent. A near real-time online dashboard will be developed to help visualize the data and share results with key policymakers. Conclusion: The designed syndromic surveillance system is low-cost and feasible to implement under COVID-19 restrictions, with no physical contact with respondents and limited movement of the study teams and communities. The system will allow estimation proportions of those reporting ILI/CLI among the general population and PLHIV on ART and monitor trends over time to detect locations with possible COVID-19 transmission. Reported household deaths in Malawi, access to health services, and COVID-19 knowledge will be monitored to assess the burden and impact on communities in Malawi.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.