Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

Clinical, pharmacological, and qualitative characterization of drug-drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa.

BACKGROUND: We investigated the impact of Drug-Drug Interactions (DDIs) on virologic control among HIV-positive pregnant women initiating antiretroviral therapy while identifying drivers for Traditional Medicine (TM) use and exploring the nature and extent of TM-related DDIs. METHODS: Employing a three-pronged approach, we examined DDIs arising from comedication, including TM, in ART. The DolPHIN-2 trial (NCT03249181) randomized 268 HIV-positive pregnant women in Uganda and South Africa to dolutegravir (DTG)-based (135) or efavirenz-based (133) regimens while systematically recording comedications and screening for DDIs. We used Cox regression models to compare time-to-virologic control between participants with and without DDIs. We conducted in-depth interviews and focus group discussions among 37 and 67 women with and without HIV, respectively, to explore reasons for TM use during pregnancy. Additionally, in-vitro and in-vivo studies evaluated the composition and impact of clay-based TM, mumbwa, on DTG plasma exposure. RESULTS: The baseline prevalence of DDIs was 67.2%, with TM use prevalent in 34% of participants, with mumbwa being the most frequent (76%, 69/91). There was no difference in virologic response between participants with and without DDIs. Fetal health and cultural norms were among the reasons cited for TM use. Analysis of mumbwa rods confirmed significant amounts of aluminium (8.4%-13.9%) and iron (4%-6%). In Balb-C mice, coadministration of mumbwa led to a reduction in DTG exposure observed in the AUC0-24 (-21%; P = 0.0271) and C24 (-53%; P = 0.0028). CONCLUSIONS: The widespread use of clay-based TM may compromise HIV treatment, necessitating medication screening and counselling to manage DDIs in pregnant women.

Association of same-sex criminalisation laws and national HIV policies with HIV testing in African MSM: an ecological single-level and multilevel cross-sectional study of sub-Saharan African countries.

BACKGROUND: HIV incidence among men who have sex with men (MSM) in sub-Saharan Africa (SSA) remains high compared with the general population. Many countries in the region still criminalise consensual homosexual relationships, and some are yet to adopt WHO-recommended interventions for MSM into national HIV policies. This study examines how HIV testing of adult MSM in SSA varies according to the legal climate and presence of targeted HIV policy using data from the cross-sectional 2019 Global LGBTI Internet Survey study. METHODS: Using data from 3191 MSM in 44 SSA countries, we assessed associations of legal climate and HIV policy with ever and recent HIV testing using linear ecological and logistic multilevel analyses. From the single-level analysis, we can compare our findings to previously reported data, then, extending to a two-level multilevel analysis, we account for the hierarchical structure of the population and simultaneously adjust for differences in context and composition in each country. We then test the sensitivity of our analyses to excluding countries from the model. RESULTS: We find evidence that legalised same-sex relationships were associated with increased odds of ever testing (OR=2.00, 95% CI 1.04, 3.82) in multilevel analyses. We also find evidence of an association of targeted HIV policies with increased odds of ever testing (OR=2.49, 95% CI 1.12, 5.52). We did not find evidence of an association of the legal climate (OR=1.01, 95% CI 0.69, 1.46) and targeted HIV policies (OR=1.26, 95% CI 0.78, 2.04) with recent testing. CONCLUSIONS: This study suggests elimination of discriminatory laws and policies might be important for increasing HIV status awareness of MSM, an important first step in epidemic control. Additionally, we highlight heterogeneity between South Africa and other SSA countries, which has implications for studying SSA countries as a homogeneous group.

Lessons learned from implementation of four HIV self-testing (HIVST) distribution models in Zambia: applying the Consolidated Framework for Implementation Research to understand impact of contextual factors on implementation.

BACKGROUND: Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. METHODS: We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. RESULTS: Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. CONCLUSION: HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution.

Four antenatal care visits by four months of pregnancy and four vital tests for pregnant mothers: impact of a community-facility health systems strengthening intervention in Migori County, Kenya.

BACKGROUND: Early attendance at antenatal care (ANC), coupled with good-quality care, is essential for improving maternal and child health outcomes. However, achieving these outcomes in sub-Saharan Africa remains a challenge. This study examines the effects of a community-facility health system strengthening model (known as 4byFour) on early ANC attendance, testing for four conditions by four months of pregnancy, and four ANC clinic visits in Migori county, western Kenya. METHODS: We conducted a mixed methods quasi-experimental study with a before-after interventional design to assess the impact of the 4byFour model on ANC attendance. Data were collected between August 2019 and December 2020 from two ANC hospitals. Using quantitative data obtained from facility ANC registers, we analysed 707 baseline and 894 endline unique ANC numbers (attendances) based on negative binomial regression. Logistic regression models were used to determine the impact of patient factors on outcomes with Akaike Information Criterion (AIC) and likelihood ratio testing used to compare models. Regular facility stock checks were undertaken at the study sites to assess the availability of ANC profile tests. Analysis of the quantitative data was conducted in R v4.1.1 software. Additionally, qualitative in-depth interviews were conducted with 37 purposively sampled participants, including pregnant mothers, community health volunteers, facility staff, and senior county health officials to explore outcomes of the intervention. The interview data were audio-recorded, transcribed, and coded; and thematic analysis was conducted in NVivo. RESULTS: There was a significant 26% increase in overall ANC uptake in both facilities following the intervention. Early ANC attendance improved for all age groups, including adolescents, from 22% (baseline) to 33% (endline, p = 0.002). Logistic regression models predicting early booking were a better fit to data when patient factors were included (age, parity, and distance to clinic, p = 0.004 on likelihood ratio testing), suggesting that patient factors were associated with early booking.The proportion of women receiving all four tests by four months increased to 3% (27/894), with haemoglobin and malaria testing rates rising to 8% and 4%, respectively. Despite statistical significance (p < 0.001), the rates of testing remained low. Testing uptake in ANC was hampered by frequent shortage of profile commodities not covered by buffer stock and low ANC attendance during the first trimester. Qualitative data highlighted how community health volunteer-enhanced health education improved understanding and motivated early ANC-seeking. Community pregnancy testing facilitated early detection and referral, particularly for adolescent mothers. Challenges to optimal ANC attendance included insufficient knowledge about the ideal timing for ANC initiation, financial constraints, and long distances to facilities. CONCLUSION: The 4byFour model of community-facility health system strengthening has the potential to improve early uptake of ANC and testing in pregnancy. Sustained improvement in ANC attendance requires concerted efforts to improve care quality, consistent availability of ANC commodities, understand motivating factors, and addressing barriers to ANC. Research involving randomised control trials is needed to strengthen the evidence on the model's effectiveness and inform potential scale up.

Support, not blame: safe partner disclosure among women diagnosed with HIV late in pregnancy in South Africa and Uganda.

BACKGROUND: HIV partner disclosure rates remain low among pregnant women living with HIV in many African countries despite potential benefits for women and their families. Partner disclosure can trigger negative responses like blame, violence, and separation. Women diagnosed with HIV late in pregnancy have limited time to prepare for partner disclosure. We sought to understand challenges around partner disclosure and non-disclosure faced by women diagnosed with HIV late in pregnancy in South Africa and Uganda and to explore pathways to safe partner disclosure. METHODS: We conducted in-depth interviews and focus group discussions with pregnant women and lactating mothers living with HIV (n = 109), disaggregated by antenatal care (ANC) initiation before and after 20 weeks of gestation, male partners (n = 87), and health workers (n = 53). All participants were recruited from DolPHIN2 trial sites in Kampala (Uganda) and Gugulethu (South Africa). Topic guides explored barriers to partner disclosure, effects of non-disclosure, strategies for safe disclosure. Using the framework analysis approach, we coded and summarised data based on a socio-ecological model, topic guides, and emerging issues from the data. Data was analysed in NVivo software. RESULTS: Our findings illustrate pregnant women who initiate ANC late experience many difficulties which are compounded by the late HIV diagnosis. Various individual, interpersonal, community, and health system factors complicate partner disclosure among these women. They postpone or decide against partner disclosure mainly for own and baby's safety. Women experience stress and poor mental health because of non-disclosure while demonstrating agency and resilience. We found many similarities and some differences around preferred approaches to safe partner disclosure among female and male participants across countries. Women and male partners preferred healthcare workers to assist with disclosure by identifying the 'right' time to disclose, mentoring women to enhance their confidence and communication skills, and providing professional mediation for partner disclosure and couple testing. Increasing the number of counsellors and training them on safe partner disclosure was deemed necessary for strengthening local health services to improve safe partner disclosure. CONCLUSION: HIV diagnosis late in pregnancy amplifies existing difficulties among pregnant women. Late ANC initiation is an indicator for the likelihood that a pregnant woman is highly vulnerable and needs safeguarding. Respective health programmes should be prepared to offer women initiating ANC late in pregnancy additional support and referral to complementary programmes to achieve safe partner disclosure and good health.

Community led health promotion to counter stigma and increase trust amongst priority populations: lessons from the 2022-2023 UK mpox outbreak.

BACKGROUND: Stigma, lack of trust in authorities, and poor knowledge can prevent health-seeking behaviour, worsen physical and mental health, and undermine efforts to control transmission during disease outbreaks. These factors are particularly salient with diseases such as mpox, for which 96% of cases in the 2022-2023 UK outbreak were identified among gay, bisexual, queer and men who have sex with men (MSM). This study explored stigma and health-seeking behaviour in Liverpool through the lens of the recent mpox outbreak. METHODS: Primary sources of data were interviews with national and regional key informants involved in the mpox response, and participatory workshops with priority populations. Workshop recruitment targeted Grindr users (geosocial dating/hookup app) and at risk MSM; immigrant, black and ethnic minority MSM; and male sex workers in Liverpool. Data were analysed using a deductive framework approach, building on the Health Stigma and Discrimination Framework. RESULTS: Key informant interviews (n = 11) and five workshops (n = 15) were conducted. There were prevalent reports of anticipated and experienced stigma due to mpox public health messaging alongside high demand and uptake of the mpox vaccine and regular attendance at sexual health clinics. Respondents believed the limited impact of stigma on health-seeking behaviour was due to actions by the LGBTQ + community, the third sector, and local sexual health clinics. Key informants from the LGBTQ + community and primary healthcare felt their collective action to tackle mpox was undermined by central public health authorities citing under-resourcing; a reliance on goodwill; poor communication; and tokenistic engagement. Mpox communication was further challenged by a lack of evidence on disease transmission and risk. This challenge was exacerbated by the impact of the COVID-19 pandemic on the scientific community, public perceptions of infectious disease, and trust in public health authorities. CONCLUSIONS: The LGBTQ + community and local sexual health clinics took crucial actions to counter stigma and support health seeking behaviour during the 2022-2023 UK mpox outbreak. Lessons from rights based and inclusive community-led approaches during outbreaks should be heeded in the UK, working towards more meaningful and timely collaboration between affected communities, primary healthcare, and regional and national public health authorities.

Exploring acceptability, opportunities, and challenges of community-based home pregnancy testing for early antenatal care initiation in rural Kenya.

BACKGROUND: Many women in low- and middle-income countries, including Kenya, access antenatal care (ANC) late in pregnancy. Home pregnancy testing can enable women to detect pregnancy early, but it is not widely available. Our study explored the acceptability and potential of home pregnancy testing delivered by community health volunteers (CHV) on antenatal care initiation in rural Kenya. METHODS: This study was part of a public health intervention to improve uptake and quality of ANC. Between November and December 2020, we conducted 37 in-depth interviews involving women who tested positive or negative for a urine pregnancy test provided by CHVs; CHVs and their supervisors involved in the delivery of the pregnancy tests; facility healthcare workers; and key informants. Using Sekhon et al.'s framework of acceptability, the interviews explored participants' perceptions and experiences of home pregnancy testing, including acceptability, challenges, and perceived effects on early ANC uptake. Data were analysed thematically in NVivo12 software. RESULTS: Home pregnancy testing was well-received by women who trusted test results and appreciated the convenience and autonomy it offered. Adolescents cherished the privacy, preferring home testing to facility testing which could be a stigmatising experience. Testing enabled earlier pregnancy recognition and linkage to ANC as well as reproductive decision-making for those with undesired pregnancies. Community delivery of the test enhanced the reputation and visibility of the CHVs as credible primary care providers. CHVs in turn were motivated and confident to deliver home pregnancy testing and did not find it as an unnecessary burden; instead, they perceived it as a complement to their work in providing ANC in the community. Challenges identified included test shortages, confidentiality and safeguarding risks, and difficulties accessing facility-based care post-referral. Newly identified pregnant adolescents hesitated to seek ANC due to stigma, fear of reprimand, unwanted parental notification, and perceived pressure from healthcare workers to keep the pregnancy. CONCLUSION: Home pregnancy testing by CHVs can improve early ANC initiation in resource-poor settings. Mitigating privacy, confidentiality, and safeguarding concerns is imperative. Additional support for women transitioning from pregnancy identification to ANC is essential to ensure appropriate care. Future research should focus on integrating home pregnancy testing into routine community health services.

"Honestly, this problem has affected me a lot": a qualitative exploration of the lived experiences of people with chronic respiratory disease in Sudan and Tanzania.

BACKGROUND: Over 500 million people live with chronic respiratory diseases globally and approximately 4 million of these, mostly from the low- and middle-income countries including sub-Saharan Africa, die prematurely every year. Despite high CRD morbidity and mortality, only very few studies describe CRDs and little is known about the economic, social and psychological dimensions of living with CRDs in sub-Saharan Africa. We aimed to gain an in-depth understanding of the social, livelihood and psychological dimensions of living with CRD to inform management of CRDs in Sudan and Tanzania. METHOD: We conducted 12 in-depth interviews in 2019 with people with known or suspected CRD and 14 focus group discussions with community members in Gezira state, Sudan and Dodoma region, Tanzania, to share their understanding and experience with CRD. The data was analysed using thematic framework analysis. RESULTS: People with CRD in both contexts reported experiences under two broad themes: impact on economic wellbeing and impact on social and psychological wellbeing. Capacity to do hard physical work was significantly diminished, resulting in direct and indirect economic impacts for them and their families. Direct costs were incurred while seeking healthcare, including expenditures on transportation to health facility and procurement of diagnostic tests and treatments, whilst loss of working hours and jobs resulted in substantial indirect costs. Enacted and internalised stigma leading to withdrawal and social exclusion was described by participants and resulted partly from association of chronic cough with tuberculosis and HIV/AIDS. In Sudan, asthma was described as having negative impact on marital prospects for young women and non-disclosure related to stigma was a particular issue for young people. Impaired community participation and restrictions on social activity led to psychological stress for both people with CRD and their families. CONCLUSION: Chronic respiratory diseases have substantial social and economic impacts among people with CRD and their families in Sudan and Tanzania. Stigma is particularly strong and appears to be driven partly by association of chronic cough with infectiousness. Context-appropriate measures to address economic impacts and chronic cough stigma are urgently needed as part of interventions for chronic respiratory diseases in these sub-Saharan African contexts.

Perceived impacts of COVID-19 responses on routine health service delivery in Liberia and UK: cross-country lessons for resilient health systems for equitable service delivery during pandemics.

BACKGROUND: COVID-19 has caused significant public health problems globally, with catastrophic impacts on health systems. This study explored the adaptations to health services in Liberia and Merseyside UK at the beginning of the COVID-19 pandemic (January-May 2020) and their perceived impact on routine service delivery. During this period, transmission routes and treatment pathways were as yet unknown, public fear and health care worker fear was high and death rates among vulnerable hospitalised patients were high. We aimed to identify cross-context lessons for building more resilient health systems during a pandemic response. METHODS: The study employed a cross-sectional qualitative design with a collective case study approach involving simultaneous comparison of COVID-19 response experiences in Liberia and Merseyside. Between June and September 2020, we conducted semi-structured interviews with 66 health system actors purposively selected across different levels of the health system. Participants included national and county decision-makers in Liberia, frontline health workers and regional and hospital decision-makers in Merseyside UK. Data were analysed thematically in NVivo 12 software. RESULTS: There were mixed impacts on routine services in both settings. Major adverse impacts included diminished availability and utilisation of critical health services for socially vulnerable populations, linked with reallocation of health service resources for COVID-19 care, and use of virtual medical consultation in Merseyside. Routine service delivery during the pandemic was hampered by a lack of clear communication, centralised planning, and limited local autonomy. Across both settings, cross-sectoral collaboration, community-based service delivery, virtual consultations, community engagement, culturally sensitive messaging, and local autonomy in response planning facilitated delivery of essential services. CONCLUSION: Our findings can inform response planning to assure optimal delivery of essential routine health services during the early phases of public health emergencies. Pandemic responses should prioritise early preparedness, with investment in the health systems building blocks including staff training and PPE stocks, address both pre-existing and pandemic-related structural barriers to care, inclusive and participatory decision-making, strong community engagement, and effective and sensitive communication. Multisectoral collaboration and inclusive leadership are essential.

"You have a self-testing method that preserves privacy so how come you cannot give us treatment that does too?" Exploring the reasoning among young people about linkage to prevention, care and treatment after HIV self-testing in Southern Malawi.

BACKGROUND: Young people, aged 16-24, in southern Malawi have high uptake of HIV self-testing (HIVST) but low rates of linking to services following HIVST, especially in comparison, to older generations. The study aim is to explore the barriers and facilitators to linkage for HIV prevention and care following uptake of HIV self-testing among young Malawians. METHODS: We used qualitative methods. Young people aged 16-24 who had received HIVST; community-based distribution agents (CBDAs) and health care workers from the linked facilities were purposively sampled from two villages in rural southern Malawi. RESULTS: We conducted in-depth interviews with thirteen young people (9 female) and held four focus groups with 28 healthcare workers and CBDAs. Young people strongly felt the social consequences associated with inadvertent disclosure of HIV sero-status were a significant deterrent to linkage at their stage in life. They also felt communication on testing benefits and the referral process after testing was poor. In contrast, they valued encouragement from those they trusted, other's positive treatment experiences and having a "strength of mind". CBDAs were important facilitators for young people as they are able to foster a trusting relationship and had more understanding of the factors which prevented young people from linking following HIVST than the healthcare workers. Young people noted contextual barriers to linkage, for example, being seen on the road to the healthcare centre, but also societal gendered barriers. For example, young females and younger adolescents were less likely to have the financial independence to link to services whilst young males (aged 19-24) had the finances but lacked a supportive network to encourage linkage following testing. Overall, it was felt that the primary "responsibility" for linking to formal healthcare following self-testing is shouldered by the young person and not the healthcare system. CONCLUSIONS: Young people are happy to self-test for HIV but faced barriers to link to services following a self-test. Potential interventions for improving linkage suggested by this analysis include the establishment of youth-friendly linkage services, enhanced lines of communication between young people and healthcare providers and prioritising linkage for future interventions when targeting young people following HIVST.

Sensitivity and specificity of OraQuick® HIV self-test compared to a 4th generation laboratory reference standard algorithm in urban and rural Zambia.

BACKGROUND: HIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users' ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection. METHODS: Participants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors. RESULTS: Initial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly. Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2-96.7) and 99.7% specific (95%CI: 99.3-99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70-91.3; specificity 99.7%, 95%CI: 99.4-99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7-96.1%; specificity 100% (95%CI: 99.8-100%) had considerably lower sensitivity. CONCLUSIONS: Self-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.

'I fear my partner will abandon me': the intersection of late initiation of antenatal care in pregnancy and poor ART adherence among women living with HIV in South Africa and Uganda.

BACKGROUND: Many women in sub-Saharan Africa initiate antenatal care (ANC) late in pregnancy, undermining optimal prevention of mother-to-child-transmission (PMTCT) of HIV. Questions remain about whether and how late initiation of ANC in pregnancy is related to adherence to antiretroviral therapy (ART) in the era of national dolutegravir roll-out. METHODS: This study employed a qualitative design involving individual interviews and focus group discussions conducted between August 2018 and March 2019. We interviewed 37 pregnant and lactating women living with HIV selected purposively for early or late presentation to ANC from poor urban communities in South Africa and Uganda. Additionally, we carried out seven focused group discussions involving 67 participants in both countries. Data were analysed thematically in NVivo12. RESULTS: Women described common underlying factors influencing both late ANC initiation and poor ART adherence in South Africa and Uganda. These included poverty and time constraints; inadequate health knowledge; perceived low health risk; stigma of HIV in pregnancy; lack of disclosure; and negative provider attitudes. Most late ANC presenters reported relationship problems, lack of autonomy and the limited ability to dialogue with their partners to influence household decisions on health and resource allocation. Perception of poor privacy and confidentiality in maternity clinics was rife among women in both study settings and compounded risks associated with early disclosure of pregnancy and HIV. Women who initiated ANC late and were then diagnosed with HIV appeared to be more susceptible to poor ART adherence. They were often reprimanded by health workers for presenting late which hampered their participation in treatment counselling and festered provider mistrust and subsequent disengagement in care. Positive HIV diagnosis in late pregnancy complicated women's ability to disclose their status to significant others which deprived them of essential social support for treatment adherence. Further, it appeared to adversely affect women's mental health and treatment knowledge and self-efficacy. CONCLUSIONS: We found clear links between late initiation of ANC and the potential for poor adherence to ART based on common structural barriers shaping both health seeking behaviours, and the adverse impact of late HIV diagnosis on women's mental health and treatment knowledge and efficacy. Women who present late are a potential target group for better access to antiretrovirals that are easy to take and decrease viral load rapidly, and counselling support with adherence and partner disclosure. A combination of strengthened health literacy, economic empowerment, improved privacy and patient-provider relationships as well as community interventions that tackle inimical cultural practices on pregnancy and unfair gender norms may be required.

"It's only fatness, it doesn't kill": a qualitative study on perceptions of weight gain from use of dolutegravir-based regimens in women living with HIV in Uganda.

BACKGROUND: Dolutegravir (DTG)-based regimens have been recommended by the WHO as the preferred first-line and second-line HIV treatment in all populations. Evidence suggests an association with weight gain, particularly among black women. Our study investigated perceptions of weight gain from DTG-based regimen use on body image and adherence of antiretroviral therapy in women living with HIV (WLHIV) in Uganda. METHODS: Between April and June 2021, we conducted semi-structured interviews involving 25 WLHIV (adolescents, women of reproductive potential and post-menopausal women) and 19 healthcare professionals (clinicians, nurses, ART managers and counsellors) purposively selected from HIV clinics in Kampala. The interviews explored perceptions of body weight and image; experiences and management of weight related side effects associated with DTG; and knowledge and communication of DTG-related risks. Data was analysed thematically in NVivo 12 software. RESULTS: Our findings indicate WLHIV in Uganda commonly disliked thin body size and aspired to gain moderate to high level body weight to improve their body image, social standing and hide their sero-positive status. Both WLHIV and healthcare professionals widely associated weight gain with DTG use, although it was rarely perceived as an adverse event and was unlikely to be reported or to alter medication adherence. Clinical management and pharmacovigilance of DTG-related weight gain were hampered by the limited knowledge of WLHIV of the health risks of being over-weight and obesity; lack of diagnostic equipment and resources; and limited clinical guidance for managing weight gain and associated cardiovascular and metabolic comorbidities. CONCLUSIONS: The study highlights the significance of large body-size in promoting psychosocial wellbeing in WLHIV in Uganda. Although weight gain is recognized as a side effect of DTG, it may be welcomed by some WLHIV. Healthcare professionals should actively talk about and monitor for weight gain and occurrence of associated comorbidities to facilitate timely interventions. Improved supply of diagnostic equipment and support with sufficient guidance for managing weight gain for healthcare professionals in Uganda are recommended.

Association of anticipated HIV testing stigma and provider mistrust on preference for HIV self-testing among cisgender men who have sex with men in the Philippines.

BACKGROUND: New HIV infections in the Philippines are increasing at an alarming rate. However, over three quarters of men who have sex with men (MSM) have never been tested for HIV. HIV self-testing (HIVST) may increase overall testing rates by removing barriers, particularly fear of stigmatization and mistrust of providers. This study aimed to determine if these factors are associated with preference for HIVST among Filipino cisgender MSM (cis-MSM), and whether there is an interaction between anticipated HIV testing stigma and provider mistrust on preference for HIVST. METHODS: We conducted secondary analysis of a one-time survey of 803 cis-MSM who were recruited using purposive sampling from online MSM dating sites and MSM-themed bar locations in Metro Manila, Philippines. Summary statistics were computed to describe participant characteristics. Multivariable modified Poisson regression analyses were conducted to determine if anticipated HIV testing stigma and provider mistrust were associated with preference for HIVST among cis-MSM. Other variables such as age, education, monthly income, relationship status, HIV serostatus, and knowing where to get HIV testing were the minimal sufficient adjustment set in the analyses. RESULTS: Average age of participants was 28.6 years (SD = 8.0); most had received college degrees (73%) and were employed (80%). Most respondents (81%) preferred facility-based testing, while 19% preferred HIVST. A high percentage of participants reported anticipated HIV testing stigma (66%) and provider mistrust (44%). Anticipated HIV testing stigma (aPR = 1.51; 95% CI = 1.01-2.25, p = 0.046) and provider mistrust (aPR = 1.49; 95% CI = 1.07-2.09, p = 0.020) were independently associated with a preference for HIVST. There was a positive, additive interaction between provider mistrust and anticipated HIV testing stigma on preference for HIVST (RERI = 1.13, 95% CI: 0.20-2.06; p = 0.017), indicating that the association between anticipated HIV testing stigma and preference for HIVST is greater among those with provider mistrust compared to those without provider mistrust. CONCLUSIONS: HIVST should be offered as a supplement to traditional facility-based HIV testing services in the Philippines to expand testing and reach individuals who may not undergo testing due to anticipated HIV testing stigma and provider mistrust.

"Deadly", "fierce", "shameful": notions of antiretroviral therapy, stigma and masculinities intersecting men's life-course in Blantyre, Malawi.

BACKGROUND: Stigma and masculinity represent persistent barriers in delivering successful HIV interventions to men. Our study examined community perceptions of HIV and anti-retroviral therapy (ART) and their implications for men on ART across the life course in Blantyre, Malawi. METHODS: Our qualitative study is based on 72 face-to-face semi-structured interviews. Participants were selected purposively and included men on ART (with suppressed and unsuppressed viral loads), adult male community members irrespective of HIV status and other HIV stakeholders such as health personnel and program implementers. Interviews were conducted in Chichewa and English, transcribed verbatim and analyzed thematically in NVivo 12. We applied the socio-ecological model as our theoretical framework as well as a "life-course" perspective. RESULTS: Our findings highlight lingering negative perceptions towards ART in general and towards PLHIV irrespective of viral load suppression. With intersecting notions of masculinity and stigma, men's descriptions of anticipated stigma in their relationships and when visiting health facilities dominated. Stigma was experienced at the personal, interpersonal, facility and community level. Yet, men living with HIV were perceived differently throughout the life-course, with young sexually active men seen as the most stigmatized group and older men seen as drawing resilience from a greater range of masculine norms. Some men of all ages displayed "transformative" masculinities independent of stigma and community expectations. CONCLUSIONS: We propose the "life-course" as a useful concept for studies on masculinity, HIV and stigma. Considering gendered constructions of "respectable" midlife-older age vis-à-vis younger age, and how they influence stigma as well as uptake and adherence to ART might lead to more targeted services for men that build on "transformative masculinities".

'Too old to test?': A life course approach to HIV-related risk and self-testing among midlife-older adults in Malawi.

BACKGROUND: Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults. METHODS: We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older (≥30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIV self-testing (HIVST) to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations. RESULTS: Midlife-older adults (30-74 years of age) associated their age with respectability and identified HIV as "a disease of youth" that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying "lack of wisdom". These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults. CONCLUSIONS: Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.

Management of chronic lung diseases in Sudan and Tanzania: how ready are the country health systems?

BACKGROUND: Chronic lung diseases (CLDs), responsible for 4 million deaths globally every year, are increasingly important in low- and middle-income countries where most of the global mortality due to CLDs currently occurs. As existing health systems in resource-poor contexts, especially sub-Saharan Africa (SSA), are not generally oriented to provide quality care for chronic diseases, a first step in re-imagining them is to critically consider readiness for service delivery across all aspects of the existing system. METHODS: We conducted a mixed-methods assessment of CLD service readiness in 18 purposively selected health facilities in two differing SSA health system contexts, Tanzania and Sudan. We used the World Health Organization's (WHO) Service Availability and Readiness Assessment checklist, qualitative interviews of key health system stakeholders, health facility registers review and assessed clinicians' capacity to manage CLD using patient vignettes. CLD service readiness was scored as a composite of availability of service-specific tracer items from the WHO service availability checklist in three domains: staff training and guidelines, diagnostics and equipment, and basic medicines. Qualitative data were analysed using the same domains. RESULTS: One health facility in Tanzania and five in Sudan, attained a CLD readiness score of ≥ 50 % for CLD care. Scores ranged from 14.9 % in a dispensary to 53.3 % in a health center in Tanzania, and from 36.4 to 86.4 % in Sudan. The least available tracer items across both countries were trained human resources and guidelines, and peak flow meters. Only two facilities had COPD guidelines. Patient vignette analysis revealed significant gaps in clinicians' capacity to manage CLD. Key informants identified low prioritization as key barrier to CLD care. CONCLUSIONS: Gaps in service availability and readiness for CLD care in Tanzania and Sudan threaten attainment of universal health coverage in these settings. Detailed assessments by health systems researchers in discussion with stakeholders at all levels of the health system can identify critical blockages to reimagining CLD service provision with people-centered, integrated approaches at its heart.

Using research networks to generate trustworthy qualitative public health research findings from multiple contexts.

BACKGROUND: Qualitative research networks (QRNs) bring together researchers from diverse contexts working on multi-country studies. The networks may themselves form a consortium or may contribute to a wider research agenda within a consortium with colleagues from other disciplines. The purpose of a QRN is to ensure robust methods and processes that enable comparisons across contexts. Under the Self-Testing Africa (STAR) initiative and the REACHOUT project on community health systems, QRNs were established, bringing together researchers across countries to coordinate multi-country qualitative research and to ensure robust methods and processes allowing comparisons across contexts. QRNs face both practical challenges in facilitating this iterative exchange process across sites and conceptual challenges interpreting findings between contexts. This paper distils key lessons and reflections from both QRN experiences on how to conduct trustworthy qualitative research across different contexts with examples from Bangladesh, Ethiopia, Kenya, Indonesia, Malawi, Mozambique, Zambia and Zimbabwe. METHODS: The process of generating evidence for this paper followed a thematic analysis method: themes initially identified were refined during several rounds of discussions in an iterative process until final themes were agreed upon in a joint learning process. RESULTS: Four guiding principles emerged from our analysis: a) explicit communication strategies that sustain dialogue and build trust and collective reflexivity; b) translation of contextually embedded concepts; c) setting parameters for contextualizing, and d) supporting empirical and conceptual generalisability. Under each guiding principle, we describe how credibility, dependability, confirmability and transferability can be enhanced and share good practices to be considered by other researchers. CONCLUSIONS: Qualitative research is often context-specific with tools designed to explore local experiences and understandings. Without efforts to synthesise and systematically share findings, common understandings, experiences and lessons are missed. The logistical and conceptual challenges of qualitative research across multiple partners and contexts must be actively managed, including a shared commitment to continuous 'joint learning' by partners. Clarity and agreement on concepts and common methods and timelines at an early stage is critical to ensure alignment and focus in intercountry qualitative research and analysis processes. Building good relationships and trust among network participants enhance the quality of qualitative research findings.

"I wanted evidence that my status had changed, so that is why I tested": experiences with HIV self-testing among female sex workers in Malawi.

HIV testing among female sex workers (FSWs) is an established global health priority. HIV self-testing (HIVST) seems to have the potential to address issues of confidentiality, privacy and convenience among this key population. HIVST, however, may result in unintended consequences as its implementation unfolds in a complex sex work context characterised by unequal power relations, stigma and high HIV prevalence. We aimed to explore the experiences of FSWs with HIVST in the context of retesting and antiretroviral usage in Blantyre, Malawi. We used an ethnographic approach to understand meanings and views around HIVST and retesting. We found high levels of retesting, especially among those on antiretroviral, two of which received "false-negative" results. We identified three broad narratives: (1) retesting in response to experiences in the sex work context, (2) retesting driven by the desire to self-monitor HIV-negative status, and (3) retesting in the hope of sero-reversion. The FSWs' experiences indicate that the implementation of HIVST in this context is complex with potential for unintended harms such as coercive testing. HIVST programmes must include clear and appropriate messaging to reduce retesting while on ART and implement strategies to address FSW concerns and anxieties about the accuracy of their HIV-positive test results.