High HIV Prevalence Settings Research Articles

Risk factors for severe respiratory syncytial virus-associated respiratory tract infection in a high HIV prevalence setting, South Africa, 2012 – 2018

BackgroundIdentifying risk factors for respiratory syncytial virus (RSV)–associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions.MethodsUsing surveillance data from South Africa (2012–2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis.ResultsRSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2–4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5–125.8), malnutrition (aOR 1.9; 95% CI 1.2–3.2), prematurity (aOR 2.4; 95% CI 1.3–4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9–174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5–24 years (aOR 10.7; 95% CI 1.1–107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1–6.3), underlying illness (aOR 2.7; 95% CI 1.5–26.1) and LWH (aOR 16.8, 95% CI: 4.8–58.2).ConclusionIndividuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions.Clinical trial numberNot applicable, this is not a clinical trial.

Preferences for pre-exposure prophylaxis delivery via online pharmacy among potential users in Kenya: a discrete choice experiment.

Oral pre-exposure prophylaxis (PrEP) is highly effective, but coverage remains low in high HIV prevalence settings. Initiating and continuing PrEP remotely via online pharmacies is a promising strategy to expand PrEP uptake, but little is known about potential users' preferences. We conducted a discrete choice experiment (DCE) to assess preferences for online pharmacy PrEP services. We partnered with MYDAWA, an online pharmacy in Nairobi, Kenya. Eligibility criteria were: ≥18 years, not known HIV positive, interested in PrEP. The DCE contained four attributes: PrEP eligibility assessment (online self-assessed, guided), HIV test type (provider administered, oral HIV self-test [HIVST], blood-based HIVST), clinical consultation (remote, in-person) and user support options (text messages, phone/video call, email). Additionally, participants indicated whether they were willing to uptake their selected service. The survey was advertised on MYDAWA's website; interested participants met staff in-person at a convenient location to complete the survey from 1 June to 20 November 2022. We used conditional logit modelling with an interaction by current PrEP use to estimate overall preferences and latent class analysis (LCA) to assess preference heterogeneity. Overall, 772 participants completed the DCE; the mean age was 25 years and 54% were female. Most participants indicated a willingness to acquire online PrEP services, with particularly high demand among PrEP-naive individuals. Overall, participants preferred remote clinical consultation, HIV self-testing, online self-assessment and phone call user support. The LCA identified three subgroups: the "prefer online PrEP with remote components" group (60.3% of the sample) whose preferences aligned with the main analysis, the "prefer online PrEP with in-person components" group (20.7%), who preferred in-person consultation, provider-administered HIV testing, and guided assessment, and the "prefer remote PrEP (18.9%)" group who preferred online PrEP services only if they were remote. Online pharmacy PrEP is highly acceptable and may expand PrEP coverage to those interested in PrEP but not accessing services. Most participants valued privacy and autonomy, preferring HIVST and remote provider interactions. However, when needing support for questions regarding PrEP, participants preferred phone/SMS contact with a provider. One-fifth of participants preferred online PrEP with in-person components, suggesting that providing multiple options can increase uptake.

Computed Tomography of the Head Before Lumbar Puncture in Adults With Suspected Meningitis in High-HIV Prevalence Settings.

The role of computed tomography (CT) before lumbar puncture (LP) is unclear, with limited evidence for a causal link between LP and cerebral herniation or for the ability of CT to identify individuals at risk of herniation. The risks of LP delay or deferral are potentially greater in high-HIV prevalence, resource-limited settings; we analyzed data from such a setting to determine the impact of CT on time to LP and treatment, as well as mortality. Adults with suspected central nervous system (CNS) infection were enrolled prospectively into the Botswana National Meningitis Survey between 2016 and 2019. Inpatient mortality and clinical data including time of treatment initiation and CT were captured from medical records. Associations between preceding CT and outcomes were assessed using logistic regression. LPs were performed in 711 patients with suspected CNS infection; 27% had a CT before LP, and 73% were HIV positive. Time from admission to LP and time from admission to appropriate treatment were significantly longer in patients who had a CT before LP compared with those who did not (2.8 hours and 13.2 hours, respectively). There was some evidence for treatment delays being associated with increased mortality; however, there was no significant difference in mortality between those who had or did not have CT. Patients who had a CT had delays to diagnostic LP and initiation of appropriate treatment; although treatment delays were associated with increased mortality, our observational study could not demonstrate a causal association between delays in diagnosis and treatment introduced by CT and mortality.

Dynamic HIV risk differentiation among youth: Validation of a tool for prioritization of prevention in East Zimbabwe.

Differentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth. Population-based household survey in east Zimbabwe. HIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories. In total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months. The refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.

Balancing risk and reward: exploring women’s transactional sexual relationships with Blessers in South Africa

Transactional sexual relationships (TSRs) take varied forms, with research emphasizing TSRs’ inherent risks, primarily to women. In South Africa, Blessed relationships have emerged as a prominent type of TSR. Blessers have become coveted male partners due to their relative wealth and willingness to ‘bless’ female partners with financial and material gifts, as well as the improved social status that accompanies such partnerships. Given the limited literature on Blesser partnerships, we investigated women’s implicit and explicit negotiated rewards and their perceived risk and ability to employ risk mitigation strategies, utilizing risk as a sociological concept to enhance understanding of risks women assume, and subsequent gendered implications. This qualitative study was conducted in 2017-2018 in KwaZulu-Natal (KZN) province, South Africa, a high HIV prevalence setting, with 22 women, using purposive and snowball sampling methods. We found that women in relationships with a Blesser recognize and navigate a number of risks, including: the threat of HIV acquisition, falling pregnant, experiencing an emotional void following a TSR, and expressed feelings of guilt and shame, as segments of South African society remain judgmental of TSRs. These risks are then weighed against the pursuit of sustained financial and social rewards achieved through such relationships.

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London. Evidence before this study: Blood RNA biomarker signatures and CRP measurements have emerged as potential triage tests for TB, but evidence is mostly limited to their performance in pulmonary TB. Microbiological diagnosis of extrapulmonary TB (EPTB) is made challenging by the need for invasive sampling to obtain tissue from the site of disease. This is compounded by lower sensitivity of confirmatory molecular tests for EPTB compared to their performance in pulmonary disease. We performed a systematic review of diagnostic accuracy studies of blood RNA biomarkers or CRP measurements for EPTB, which could mitigate the need for site-of-disease sampling for the diagnosis of TB. We searched PubMed up to 1 st August 2023, using the following criteria: "extrapulmonary [title/abstract] AND tuberculosis [title/abstract] AND biomarker [title/abstract]". Although extrapulmonary TB was included in several studies, none focused specifically on EPTB or included an adequate number of EPTB cases to provide precise estimates of test accuracy. Added value of this study: To the best of our knowledge, we report the first diagnostic accuracy study of blood RNA biomarkers and CRP for TB among people with EPTB syndromes. We examined the performance of seven previously identified blood RNA biomarkers as triage tests for TB lymphadenitis and TB pericarditis compared to a microbiology reference standard among people referred to hospital for invasive sampling in a high TB and HIV prevalence setting. Multiple blood RNA biomarkers showed comparable diagnostic accuracy to that previously reported for pulmonary TB in both EPTB disease cohorts, irrespective of HIV status. All seven blood RNA biomarkers showed superior diagnostic accuracy to CRP for both lymphadenitis and pericarditis, but failed to meet the combined >90% sensitivity and >70% specificity recommended for a blood-based diagnostic triage test by WHO. Nonetheless, in decision curve analysis, an approach of using the best performing blood RNA biomarker to trigger confirmatory microbiological testing showed superior clinical utility in clinical services seeking to reduce the number needed to test (using invasive confirmatory testing) to less than 4 for each EPTB case detected. If acceptable to undertake invasive testing in more than 4 people for each true case detected, then a test-all approach will provide greater net benefit in this TB/HIV hyperendemic setting.Implications of all the available evidence: Blood RNA biomarkers show some potential as diagnostic triage tests for TB lymphadenitis and TB pericarditis, but do not provide the level of accuracy for blood-based triage tests recommended by WHO for community-based tests. CRP has inferior diagnostic accuracy to blood RNA biomarkers and cannot be recommended for diagnostic triage among people with EPTB syndromes referred for invasive sampling.

Health System Responses to Address Treatment Gaps of Unsuppressed Adolescents on HIV Treatment in Public Primary Health Care Facilities in Windhoek, Namibia.

Adolescents living with HIV (ALHIV) face unique challenges that result in persistent gaps in achieving and maintaining suppressed viral load. Although effective evidence-based interventions to address treatment gaps in adolescents are readily available, health systems in resource-constrained, high HIV prevalence settings are challenged to implement them to achieve epidemic control. Here, we describe the health system responses to address the treatment gap of unsuppressed ALHIV on antiretroviral therapy in Windhoek, Namibia. We conducted a qualitative descriptive and exploratory study in Windhoek between June and October 2023. Nineteen purposively selected key informants, ranging from pediatric HIV program managers to healthcare providers, were interviewed. In-depth interviews were audio-recorded and transcribed verbatim. The transcripts were uploaded to ATLAS.ti and subjected to thematic analysis. The four main themes elucidated challenges related to adherence and retention as well as health system responses in the form of interventions and support programs. The predominant adherence and retention challenges faced by ALHIV were mental health issues, behavioral and medication-related challenges, and inadequate care and social support. The health system responses to the identified challenges included providing psychosocial support, peer support, optimization of treatment and care, and the utilization of effective service delivery models. Key health system support elements identified included adequately capacitated human resources, efficient medication supply chain systems, creating and maintaining an enabling environment for optimum care, and robust monitoring systems as essential to program success. The health system responses to address the remaining treatment gaps of unsuppressed ALHIV in Windhoek are quite varied and, although evidence-based, appear to be siloed. We recommend harmonized, multifaceted guidance, integrating psychosocial, treatment, care, and peer-led support, and strengthening client-centred differentiated service delivery models for unsuppressed adolescents.

First-Line Antituberculosis Drug Challenge Reactions in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome in an HIV Endemic Setting

BackgroundIn high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. ObjectiveWe aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. MethodsPatients hospitalized with FLTD-associated DRESS from 2013–2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. ResultsSADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. ConclusionsSADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.

Mobile Phone-Based Confidential Social Network Referrals for HIV Testing (CONSORT): Protocol for a Randomized Controlled Trial.

Critical to efforts to end the HIV epidemic is the identification of persons living with HIV who have yet to be diagnosed and engaged in care. Expanded HIV testing outreach efforts need to be both efficient and ambitious, targeting the social networks of persons living with HIV and those at above-average risk of undiagnosed HIV infection. The ubiquity of mobile phones across many high HIV prevalence settings has created opportunities to leverage mobile health (mHealth) technologies to engage social networks for HIV testing outreach, prevention, and treatment. The purpose of this study is to evaluate the acceptability and efficacy of a novel mHealth intervention, "Confidential Social Network Referrals for HIV Testing (CONSORT)," to nudge at-risk individuals to test for HIV using SMS text messages. We will conduct the CONSORT study in Moshi, Tanzania, the commercial center and administrative capital of the Kilimanjaro Region in northern Tanzania. After qualitative formative work and pilot testing, we will enroll 400 clients presenting for HIV counseling and testing and 200 persons living with HIV and receiving care at HIV care and treatment centers as "inviters" into a randomized controlled trial. Eligible participants will be aged 18 years or older and live, work, or regularly receive care in Moshi. We will randomize inviters into 1 of 2 study arms. All inviters will be asked to complete a survey of their HIV testing and risk behaviors and to think of social network contacts who would benefit from HIV testing. They will then be asked to whom they would prefer to extend an HIV testing invitation in the form of a physical invitation card. Arm 1 participants will also be given the opportunity to extend CONSORT invitations in the form of automated confidential SMS text messages to any of their social network contacts or "invitees." Arm 2 participants will be offered physical invitation cards alone. The primary outcome will be counselor-documented uptake of HIV testing by invitees within 30 days of inviter enrollment. Secondary outcomes will include the acceptability of CONSORT among inviters, the number of new HIV diagnoses, and the HIV risk of invitees who present for testing. Enrollment in the randomized controlled trial is expected to start in September 2024. The findings will be disseminated to stakeholders and published in peer-reviewed journals. If CONSORT is acceptable and effective for increasing the uptake of HIV testing, given the minimal costs of SMS text reminders and the potential for exponential but targeted growth using chain referrals, it may shift current practices for HIV testing programs in the area. ClincalTrials.gov NCT05967208; https://clinicaltrials.gov/study/NCT05967208. PRR1-10.2196/55068.

Prevalence and risk factors of sexually transmitted infections in the setting of a generalized HIV epidemic-a population-based study, western Kenya.

Sexually transmitted infections (STIs) cause adverse health outcomes, including increasing HIV acquisition/transmission risk. We analyzed data from an HIV biomarker and behavioral survey to estimate STI prevalence, and explore associated factors in the setting of a generalized HIV epidemic in Siaya County, western Kenya. Data were collected in March-September 2022 through face-to-face interviews using structured questionnaires; records from 9643 sexually active participants aged 13+ years were included in the analysis. We calculated weighted self-reported STI prevalence, by sex, age, and HIV status and explored associated factors using multivariable logistic regression. Median age was 37 years and 59.9% were female; HIV prevalence was 18.0%. Overall STI prevalence was 1.8%; 1.5-fold higher among males vs. females, and 2.6-fold higher among participants living with HIV vs. those without. HIV status and multiple sexual partners were independently associated with STI in both sexes. Mind-altering substance use and being circumcised were associated with STI among males. This study estimates STI prevalence in the setting of high HIV prevalence. Findings underscore the importance of: effective STI screening in HIV clinics and HIV testing and counseling in STI clinics; screening and counseling on substance use, and HIV pre-exposure prophylaxis; and intensive sexual health counseling in male circumcision programmes.

Changes Over Time in the Proportion of Advanced HIV Disease in Two High HIV Prevalence Settings in Ndhiwa (Kenya) and Eshowe (South Africa).

The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 ("treat all") and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa. Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL. Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex. The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys.

Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting

BackgroundDespite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting.MethodsPregnant women ≥ 20 weeks’ gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity.Results Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87–1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy.HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009.In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61–10.7) and 2.46 (1.07–5.34), respectively.None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule.ConclusionLow and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden.Trial registrationwww.clinicaltrials.gov, trial registration number: NCT04087239.

A baseline assessment of developmental delays among children under 5 years in a high-HIV- prevalence setting in the Cape Metropole

&#x0D; &#x0D; &#x0D; &#x0D; Background. More than 200 million children globally are at risk of not achieving the full developmental potential owing to multiple factors. HIV exposure is of particular concern as evidence suggests that children born to mothers who are HIV-positive are likely to experience developmental delays. Furthermore, the psychosocial and economic impacts of HIV, such as parental illness, poor mental health, poverty and malnutrition, also affect children’s development.&#x0D; Objective. To assess and address the developmental challenges faced by children aged 2 - 5 years living in high-HIV prevalence settings through a toy-based rehabilitation intervention and to analyse the prevalence and nature of developmental delays observed in these children using the Ages and Stages Questionnaires (ASQ-3).&#x0D; Methods. In response, the Bright Start programme was developed and implemented to target children living in high HIV-prevalence settings. In 2019, a pilot project was implemented with 90 caregiver-child dyads in Cape Town, South Africa. A baseline survey was conducted to assess developmental progression for all the children (N=141) in the care of the 90 caregivers using the Ages and Stages Questionnaires (ASQ-3) for children aged 24, 36, 48 and 60 months.&#x0D; Results. Findings showed that 64% of children had delays in at least one domain and 37% had multiple delays. More than half of the children had developmental delays in fine motor skills (51%), while gross-motor and problem-solving delays were reported for 30% and 26% of children, respectively. Communication and personal-social domain delays were observed in 17% and 14% of children, respectively.&#x0D; Conclusion. The prevalence of developmental delays among children in the programme was alarmingly high. These findings indicate that developmental delay is a serious concern for children living in high-HIV-prevalence settings. Early identification and timeous referrals of children with developmental delays are critical and may enable children to reach their full developmental potential.&#x0D; &#x0D; &#x0D; &#x0D;

Prevalence and control of hypertension in a high HIV-prevalence setting, insights from a population based study in Botswana

In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets.

Prevention-of-mother-to-child-transmission (PMTCT) program outcomes in South Africa in the pre-COVID and COVID eras

IntroductionTwo decades after implementing the Prevention of Mother to Child transmission (PMTCT) program, South Africa has still not managed to eliminate intrauterine mother-to-child (MTCT) HIV transmission. During the COVID pandemic access to maternal health services was reduced, potentially compromising the PMTCT program.MethodA retrospective record review was conducted at a midwife-run obstetric unit in a high HIV prevalence setting. Data on pregnant women who delivered between January 2019 and December 2020 were analysed to evaluate predictors for MTCT, and compare pre-COVID and COVID-era changes in maternal and infant HIV incidence and prevalence.ResultsA total of 1660 women delivered at the facility over a 24-month period (Jan 2019-Dec 2020), of whom 92.8% enrolled for antenatal care in 2019 and 94.6% in 2020. A significantly greater proportion of women were aware of their HIV status before enrolling for antenatal care in the pre-COVID (2019) than COVID (2020) period (88% vs 40.2%; p < 0.05). There was a significant increase in new HIV infection after enrolling for antenatal care during the COVID period compared to pre-COVID period (120 vs 62 women, p < 0.05). There was also a significant increase in the HIV prevalence among women who delivered during the COVID period than in the pre-COVID era (43.5% compared to 35.8%, p < 0.05). However, more than 95% of HIV-positive women initiated ART in both periods. Overall, a total of thirteen infants tested HIV positive (2.1% MTCT rate), with no difference in MTCT between 2019 and 2020. Infants born to women on antiretroviral therapy (ART) were 93% less likely to have a positive PCR test than those whose mothers who were not on ART. (OR = 0.07, 95% CI 0.031:0.178, p < 0.05).ConclusionThe increase in maternal HIV incidence and prevalence during the COVID era suggest a lapse in HIV prevention strategies during the COVID pandemic. There is an urgent need to improve community test-and-treat campaigns among women of reproductive age in the community and increase access to HIV pre-exposure prophylaxis for pregnant women, especially during periods of health crises.

The attributable fraction of respiratory syncytial virus among patients of different ages with influenza-like illness and severe acute respiratory illness in a high HIV prevalence setting, South Africa, 2012-2016

ObjectivesThe detection of respiratory syncytial virus (RSV) in upper airway samples does not necessarily infer causality of illness. We aimed to calculate the attributable fraction (AF) of RSV in clinical syndromes across age groups. MethodsUsing unconditional logistic regression models, we estimated the AF of RSV-associated influenza-like illness (ILI) and severe acute respiratory illness (SARI) cases by comparing RSV detection prevalence among ILI and SARI cases to those of healthy controls in South Africa, 2012-2016. The analysis, stratified by HIV serostatus, was conducted in the age categories <1, 1-4, 5-24, 25-44, 45-64, and ≥65 years. ResultsWe included 12,048 individuals: 2687 controls, 5449 ILI cases, and 5449 SARI cases. RSV-AFs for ILI were significant in <1, 1-4, 5-and 24, 25-44-year age groups: 84.9% (95% confidence interval [CI] 69.3-92.6%), 74.6% (95% CI 53.6-86.0%), 60.8% (95% CI 21.4-80.5%) and 64.1% (95% CI 14.9-84.9%), respectively. Similarly, significant RSV-AFs for SARI were 95.3% (95% CI 91.1-97.5) and 83.4% (95% CI 70.9-90.5) in the <1 and 1-4-year age groups respectively. In HIV-infected persons, RSV was significantly associated with ILI cases vs controls in individuals aged 5-44 years. ConclusionHigh RSV-AFs in young children confirm RSV detection is associated with severe respiratory illness in South African children, specifically infants. These estimates will assist with refining burden estimates and cost-effectiveness models.

Transmission modeling to infer tuberculosis incidence prevalence and mortality in settings with generalized HIV epidemics

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore develop a novel age-structured TB transmission model incorporating evolving demographic, HIV and antiretroviral therapy effects, and calibrate to TB prevalence and notification data from 12 African countries. We use Bayesian methods to include uncertainty for all TB model parameters, and estimate age-specific annual risks of TB infection, finding up to 16.0%/year in adults, and the proportion of TB incidence from recent (re)infection, finding a mean across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.

Measuring the impact of COVID-19 social distancing measures on sexual health behaviours and access to HIV and sexual and reproductive health services for people living with HIV in Botswana.

Uninterrupted access to HIV and sexual and reproductive health (SRH) services is essential, particularly in high HIV prevalence settings, to prevent unintended pregnancy and vertical HIV transmission. Understanding the challenges that COVID-19 and associated social distancing measures (SDMs) posed on health service access is imperative for future planning. This cross-sectional study was conducted in Botswana between January-February 2021. A web-based questionnaire was disseminated on social media as part of the International Sexual Health and REproductive Health (I-SHARE) Survey. Respondents answered questions on SRH, before and during COVID-19 SDMs. Subgroup analysis and comparison of descriptive data was performed for people living with HIV (PLWH). Of 409 participants, 65 were PLWH (80% female, 20% male). During SDMs, PLWH found it more difficult to access condoms and treatment for HIV and STIs; attend HIV appointments; and maintain adherence to antiretroviral therapy. Compared to HIV-negative women, a higher proportion of women living with HIV used condoms as their primary method of contraception (54% vs. 48%), and had lower use of long-acting reversible contraception (8% vs. 14%) and dual contraception (8% vs. 16%). Mirroring global trends, COVID-19 disrupted HIV and SRH service access in Botswana. However, in high HIV-prevalence settings, disruption may more severely impact population health with disproportionate effects on women. Integration of HIV and SRH services could build health system capacity and resilience, reduce missed opportunities for delivering SRH services to PLWH and limit the consequences of future restrictions that may cause health system disruption.

Temporal discrepancies in “rapid” HIV testing: explaining misdiagnoses at the point-of-care in Zimbabwe

BackgroundRapid diagnostic tests have revolutionized the HIV response in low resource and high HIV prevalence settings. However, disconcerting levels of misdiagnosis at the point-of-care call for research into their root causes. As rapid HIV tests are technologies that cross borders and have inscribed within them assumptions about the context of implementation, we set out to explore the (mis)match between intended and actual HIV testing practices in Zimbabwe.MethodsWe examined actual HIV testing practices through participant observations in four health facilities and interviews with 28 rapid HIV testers. As time was identified as a key sphere of influence in thematic analyses of the qualitative data, a further layer of analysis juxtaposed intended (as scripted in operating procedures) and actual HIV testing practices from a temporal perspective.ResultsWe uncover substantial discrepancies between the temporal flows assumed and inscribed into rapid HIV test kits (their intended use) and those presented by the high frequency testing and low resource and staffing realities of healthcare settings in Zimbabwe. Aside from pointing to temporal root causes of misdiagnosis, such as the premature reading of test results, our findings indicate that the rapidity of rapid diagnostic technologies is contingent on a slow, steady, and controlled environment. This not only adds a different dimension to the meaning of “rapid” HIV testing, but suggests that errors are embedded in the design of the diagnostic tests and testing strategies from the outset, by inscribing unrealistic assumptions about the context within which they used.ConclusionTemporal analyses can usefully uncover difficulties in attuning rapid diagnostic test technologies to local contexts. Such insight can help explain potential misdiagnosis ‘crisis points’ in point-of-care testing, and the need for public health initiatives to identify and challenge the underlying temporal root causes of misdiagnosis.

Safety of chemotherapy of MDR/XDR-TB patients in high HIV prevalence settings

The review used 61 literature sources to discuss 13 publications devoted to safety of treatment of HIV-associated drug-resistant tuberculosis using basic and new regimens of chemotherapy. According to the literature, no additive toxic effects were detected during treatment with anti-tuberculosis and antiretroviral drugs. According to the literature data, no additive toxic effect was found during treatment with anti-tuberculosis and antiretroviral drugs. In conditions of high prevalence of HIV, the pharmacovigilance of drug interactions in combination therapy is particularly relevant since HIV can indirectly increase the number of ADRs not only due to cross-toxicity but also severe immunosuppression, development of immune system recovery syndrome, opportunistic infections, a characteristic intoxication syndrome, a low index body weight and individual characteristics of patients in this category.