Examining barriers to antiretroviral therapy initiation in infants living with HIV in sub-Saharan Africa despite the availability of point-of-care diagnostic testing: a narrative systematic review.

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

The impact of elevated blood lead levels in children on maternal health-related quality of life.

Kabwe is a mining town in Zambia that has been ranked among "the ten most polluted places in the world" with previous findings of serious lead (Pb) pollution. In this study, we aim to examine the impact of childhood Pb poisoning on the health-related quality of life (HRQoL) of mothers in Kabwe. The HRQoL was assessed using the Short-Form 36 survey for 404 mothers coming from residences in 40 randomly selected standard enumeration areas (SEAs). Blood lead levels (BLLs) of the household members including the mothers themselves were measured. We found a significant positive correlation between the BLLs of the mothers and their children (R = 0.6385, p < 0.0001), while the BLLs of preschool-aged and school-aged children were significantly higher than those of their mothers and fathers. Using the data sets containing the BLLs of the household members, the age of the mothers, the household income, and the household SEA, we performed stepwise multiple linear regression analyses. The results showed significant negative associations between the representative BLL of household children and the BLL of preschool-aged children with the vitality and mental health scores of their mothers. Additionally, the BLL of school-aged children was only significantly associated with the mental health score of their mothers. By contrast, there was a significant negative association between the BLLs of the mothers with the social role functioning score. This suggests that elevated BLLs in children have a negative impact on the mental health conditions of their mothers regardless of the mothers' BLL.

Socio-cultural and economic barriers, and facilitators influencing men's involvement in antenatal care including HIV testing: a qualitative study from urban Blantyre, Malawi.

BACKGROUND: Male partner involvement in antenatal care (ANC) is associated with positive maternal and neonatal outcomes. However, only a handful of men attend ANC with their partners. This study aimed to understand the underlying barriers and facilitators influencing men's ANC attendance including HIV testing in Blantyre, Malawi. METHODS: Data were collected during a formative qualitative study of a cluster-randomised trial. Six focus group discussions (FGDs) with 42 men and women and 20 in-depth interviews (IDIs) were conducted at three primary health centres in urban Blantyre, Malawi. FGD participants were purposively sampled with IDI participants subsequently sampled after FGD participation. Thematic analysis was used to analyse the data. RESULTS: The economic requirement to provide for their families exerted pressure on men and often negatively affected their decision to attend ANC together with their pregnant partners despite obvious benefits. Peer pressure and the fear to be seen by peers queueing for services at ANC, an environment traditionally viewed as a space for women and children made men feel treated as trespassers and with some level of hostility rendering them feeling emasculated when they attend ANC. Health system problems associated with overall organization of the ANC services, which favours women created resistance among men to be involved. An association between ANC and HIV testing services discouraged men from attending ANC because of their fear of testing HIV-positive in the presence of their partners. The availability of a male friendly clinic offering a private, quick, supportive/sensitive and flexible service was considered to be an important incentive that would facilitate men's ANC attendance. Men described compensation to cover transport and opportunity cost for attending the clinic as a motivator to attending ANC services and accepting an HIV test. CONCLUSION: Peer and economic influences were the most influential barriers of men attending ANC and testing for HIV with their pregnant partners. Addressing these socio-economic barriers and having a male friendly clinic are promising interventions to promote male ANC attendance in this setting.

Exploring social harms during distribution of HIV self-testing kits using mixed-methods approaches in Malawi.

INTRODUCTION: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. METHODS: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as "serious") was used to grade SH severity, assuming more complete passive reporting for serious events. RESULTS: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered "well-intentioned" within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. CONCLUSIONS: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both "active" and "passive" reporting systems identified serious SH events, although with more complete capture by "active" systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution.

HIV self-testing alone or with additional interventions, including financial incentives, and linkage to care or prevention among male partners of antenatal care clinic attendees in Malawi: An adaptive multi-arm, multi-stage cluster randomised trial.

BACKGROUND: Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial. METHODS AND FINDINGS: An adaptive multi-arm, 2-stage cluster randomised trial was conducted between 8 August 2016 and 30 June 2017, with antenatal care clinic (ANC) days (i.e., clusters of women attending on a single day) as the unit of randomisation. Recruitment was from Ndirande, Bangwe, and Zingwangwa primary health clinics in urban Blantyre, Malawi. Women attending an ANC for the first time for their current pregnancy (regardless of trimester), 18 years and older, with a primary male partner not known to be on ART were enrolled in the trial after giving consent. Randomisation was to either the standard of care (SOC; with a clinic invitation letter to the male partner) or 1 of 5 intervention arms: the first arm provided women with 2 HIVST kits for their partners; the second and third arms provided 2 HIVST kits along with a conditional fixed financial incentive of $3 or $10; the fourth arm provided 2 HIVST kits and a 10% chance of receiving $30 in a lottery; and the fifth arm provided 2 HIVST kits and a phone call reminder for the women's partners. The primary outcome was the proportion of male partners who were reported to have tested for HIV and linked into care or prevention within 28 days, with referral for antiretroviral therapy (ART) or circumcision accordingly. Women were interviewed at 28 days about partner testing and adverse events. Cluster-level summaries compared each intervention versus SOC using eligible women as the denominator (intention-to-treat). Risk ratios were adjusted for male partner testing history and recruitment clinic. A total of 2,349/3,137 (74.9%) women participated (71 ANC days), with a mean age of 24.8 years (SD: 5.4). The majority (2,201/2,233; 98.6%) of women were married, 254/2,107 (12.3%) were unable to read and write, and 1,505/2,247 (67.0%) were not employed. The mean age for male partners was 29.6 years (SD: 7.5), only 88/2,200 (4.0%) were unemployed, and 966/2,210 (43.7%) had never tested for HIV before. Women in the SOC arm reported that 17.4% (71/408) of their partners tested for HIV, whereas a much higher proportion of partners were reported to have tested for HIV in all intervention arms (87.0%-95.4%, p < 0.001 in all 5 intervention arms). As compared with those who tested in the SOC arm (geometric mean 13.0%), higher proportions of partners met the primary endpoint in the HIVST + $3 (geometric mean 40.9%, adjusted risk ratio [aRR] 3.01 [95% CI 1.63-5.57], p < 0.001), HIVST + $10 (51.7%, aRR 3.72 [95% CI 1.85-7.48], p < 0.001), and phone reminder (22.3%, aRR 1.58 [95% CI 1.07-2.33], p = 0.021) arms. In contrast, there was no significant increase in partners meeting the primary endpoint in the HIVST alone (geometric mean 17.5%, aRR 1.45 [95% CI 0.99-2.13], p = 0.130) or lottery (18.6%, aRR 1.43 [95% CI 0.96-2.13], p = 0.211) arms. The lottery arm was dropped at interim analysis. Overall, 46 male partners were confirmed to be HIV positive, 42 (91.3%) of whom initiated ART within 28 days; 222 tested HIV negative and were not already circumcised, of whom 135 (60.8%) were circumcised as part of the trial. No serious adverse events were reported. Costs per male partner who attended the clinic with a confirmed HIV test result were $23.73 and $28.08 for the HIVST + $3 and HIVST + $10 arms, respectively. Notable limitations of the trial included the relatively small number of clusters randomised to each arm, proxy reporting of the male partner testing outcome, and being unable to evaluate retention in care. CONCLUSIONS: In this study, the odds of men's linkage to care or prevention increased substantially using conditional fixed financial incentives plus partner-delivered HIVST; combinations were potentially affordable. TRIAL REGISTRATION: ISRCTN 18421340.

Acceptability of woman-delivered HIV self-testing to the male partner, and additional interventions: a qualitative study of antenatal care participants in Malawi.

INTRODUCTION: In the era of ambitious HIV targets, novel HIV testing models are required for hard-to-reach groups such as men, who remain underserved by existing services. Pregnancy presents a unique opportunity for partners to test for HIV, as many pregnant women will attend antenatal care (ANC). We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered, alone or with an additional intervention. METHODS: A formative qualitative study to inform the design of a multi-arm multi-stage cluster-randomized trial, comprised of six focus group discussions and 20 in-depth interviews, was conducted. ANC attendees were purposively sampled on the day of initial clinic visit, while men were recruited after obtaining their contact information from their female partners. Data were analysed using content analysis, and our interpretation is hypothetical as participants were not offered self-test kits. RESULTS: Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men. Men preferred this approach compared with standard facility-based testing, as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures, including the need to raise money for food for their household daily. Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur. Most men stated a preference to first self-test alone, followed by testing as a couple. Regarding interventions for optimizing linkage following self-testing, both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage. However, there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing. In this low-income setting, a lottery incentive was considered overly disappointing for those who receive nothing. Phone call reminders were preferred to short messaging service. CONCLUSIONS: Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners. Feedback on additional linkage enablers will be used to alter pre-planned trial arms.