Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

Proportion of HIV exposed infants aged 0-6 months that missed nevirapine prophylaxis in Mulago National Referral Hospital, Uganda: a cross-sectional study.

BACKGROUND: Nevirapine prophylaxis has been found to lower the risk of HIV transmission in breastfed infants. While about 95% of HIV positive pregnant and lactating mothers use Antiretroviral therapy in Uganda, a smaller percentage of HIV exposed infants (HEI) receive nevirapine (NVP) prophylaxis. This study aimed to determine the proportion of HEI who missed NVP prophylaxis and associated factors. METHODS: This was a cross-sectional study done using quantitative methods, conducted at Mulago National Referral Hospital (MNRH). A total of 228 mother-infant pairs were enrolled. The proportion of HEI who missed NVP, maternal, infant and health facility factors associated were determined using a pre-tested questionnaire. Bivariate analysis and binary logistic regression model were used to determine the proportion and factors associated with missing NVP prophylaxis. RESULTS: The proportion of HEI who missed NVP prophylaxis was 50/228 (21.9%). Factors significantly associated with HEI missing NVP prophylaxis included delivery from outside government health facilities (AOR = 8.41; P = 0.001), mothers not undergoing PMTCT counselling (AOR = 12.01; P = 0.001), not on ART (AOR = 8.47; P = 0.003) and not having disclosed their HIV status to their partners (AOR = 2.80; P = 0.001). The HEI that missed nevirapine and were HIV positive were 35 (70.0%). The HEI that were HIV infected despite receiving nevirapine prophylaxis were 5 out of 40(12.5%). CONCLUSION: One in five HEI missed NVP prophylaxis and nearly three quarters of those who missed NVP prophylaxis were HIV infected. Improving uptake of nevirapine by HEI will require interventions that can aid to strengthen PMTCT counselling.

The prevalence of vertical transmission of human immunodeficiency virus and associated factors among exposed infants in Eastern Lake zone and Southern Highland of Tanzania: a cross-sectional study.

BACKGROUND: Globally, the rate of antiretroviral therapy coverage for pregnant women living with human immunodeficiency virus (HIV) increased by 38% between 2010 and 2015 but only by 2% between 2016 and 2020. OBJECTIVES: We aimed to determine the prevalence of vertical transmission of HIV among infants from mothers living with HIV and associated factors in the Eastern Lake Zone and Southern Highland of Tanzania from January to December 2022. METHODS: This retrospective cross-sectional study extracted data from the Open Laboratory Data Repository database collected from January to December 2022 at 93 health facilities. A total of 1,411 infants exposed to HIV from the Mbeya (851), Songwe (304), and Mara regions (256) were enrolled. RESULTS: The prevalence for vertical transmission of HIV was 2.48% (35/1411). We observed a non-significant difference in the prevalence of vertical transmission in children whose first test was done below six weeks of life (1.89%) and other age groups (2.52-2.62%) (p < 0.917). Children not given antiretroviral prophylaxis had eleven times higher odds of acquiring infection (AOR 11.39, 95% CI: 3.61-35.97). Mothers who were not on ART during pregnancy had three times the odds of transmitting HIV to their infants (AOR 3.03, 95%CI: 0.91-10.15). CONCLUSIONS: We found a low prevalence of vertical transmission of HIV compared to previous studies done in Tanzania. The use of ART prophylaxis for infants exposed to HIV is significantly associated with the low rate of HIV transmission.

Feeding modalities, HIV transmission and its predictors among HIV-exposed infants visited Gamo and Gofa zones public health facilities, Southern Ethiopia: a retrospective follow up study.

BACKGROUND: Despite the highest (88%) Prevention of Mother-To-Child Transmission (PMTCT) of HIV coverage in Eastern Africa, 50% of new HIV infections in children aged 0-14 years occur in the region. OBJECTIVE: The aim of this study was to assess the feeding modalities, the rate of HIV transmission and its predictors among HIV exposed infants (HIV-EIs) visited Gamo and Gofa Zones public health facilities, Southern Ethiopia from January 2013 to February 2019. METHOD AND MATERIALS: Institution-based retrospective follow up study was employed among 450 HIV-EIs having DNA/PCR test results. All infant-mother pair records in selected health facilities were reviewed using a standard data extraction tool from March to July 2019. HIV transmission probabilities were assessed by Kaplan-Meier time-to-event analysis method and log-rank tests were used to compare the risk among different groups. The Cox-proportional hazards model, adjusted on infant feeding modalities and other co-variants was used to identify predictors of HIV transmission, and statistical significance was declared at a p-value of < 0.05. RESULTS: In total, 383 complete records were analyzed. In the study, 85.6% (95%CI: 81.6%, 89.1%) of HIV-EIs were exclusively breastfed in the first six months. The 18 months probability of infant HIV transmission was 64 (16.7%) (95%CI: 13.1%-20.8%). The risk of HIV-transmission was higher among infants who were delivered at the hospital than health centers/health posts (AHR = 3.07; 95%CI: 1.19, 7.95); discontinued Cotrimoxazole prophylaxis in at least one visit (AHR = 6.32; 95%CI: 3.35, 11.94); did not exclusively breastfeed (AHR = 3.07; 95%CI: 1.72, 5.47) and came from urban areas (AHR = 5.90; 95%CI: 1.40, 24.85). CONCLUSIONS: The study showed that HIV-EIs had a greater rate of 18 months HIV transmission than the national pooled prevalence. The risk of transmission is higher among infants who do not breastfeed exclusively for the first 6 months, and the risk increases with the number of months spent by breastfeeding. Therefore, strengthening counselling on safer feeding options and Cotrimoxazole prophylaxis use; provision of quality PMTCT service with special focus in hospitals and urban residents were recommended.

Factors associated with exclusive breastfeeding by maternal HIV status: a population-based survey in Kenya.

BACKGROUND: Exclusive breastfeeding (EBF) in the first six months remains low globally, despite known benefits of lower morbidity and mortality among breastfed infants. It is important to understand factors associated with breastfeeding to support optimal breastfeeding practices, particularly in settings with a high burden of HIV. METHODS: We analyzed data from a population-level survey of mother-infant pairs attending 6-week or 9-month immunizations at 141 clinics across Kenya. Primary outcomes included maternal report of (1) EBF at 6-week visit, defined as currently feeding the infant breast milk only, (2) EBF for the first 6-months of life, defined as breastfeeding or feeding the infant breast milk only with no introduction of other liquids or solid foods until 6 months, and (3) continued breastfeeding with complementary feeding at 9-months. Correlates of breastfeeding practices were assessed using generalized Poisson regression models accounting for facility-level clustering. RESULTS: Among 1662 mothers at 6-weeks, nearly all self-reported breastfeeding of whom 93% were EBF. Among 1180 mothers at 9-months, 99% had ever breastfed, 94% were currently breastfeeding and 73% reported 6-month EBF. At 6-weeks, younger age (< 25 years) (adjusted Prevalence Ratio (aPR) 0.96; 95% CI 0.93, 0.99), lower education (aPR 0.96; 95% CI 0.93, 0.99) and recent infant illness (aPR 0.97; 95% CI 0.94, 1.00) were associated with lower EBF prevalence while women living with HIV (WLWH) had higher EBF prevalence (aPR 1.06; 95% CI 1.02, 1.10) than women without HIV. 6-month EBF prevalence was 26% higher in WLWH (aPR 1.26; 95% CI 1.15, 1.35) than women without HIV, 14% lower in women reporting mild or above depressive symptoms (aPR 0.86; 95% CI 0.76, 0.99) than those with none or minimal depressive symptoms, and 15% lower in women with versus without history of intimate partner violence (aPR 0.85; 95% CI 0.74, 0.98). At 9-months, WLWH had a lower prevalence of continued breastfeeding with complementary feeding (aPR 0.73; 95% CI 0.64, 0.84) than women without HIV. CONCLUSION: WLWH had higher EBF prevalence in the first 6-months, but lower prevalence of continued breastfeeding at 9-months. Strategies to support EBF and continued breastfeeding beyond 6-months postpartum, particularly among WLWH, are needed.

Magnitude and risk factors of mother-to-child transmission of HIV among HIV-exposed infants after Option B+ implementation in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) remains a major public health challenge in Ethiopia. The objective of this review was to assess the pooled magnitude of MTCT of HIV and its risk factors among mother-infant pairs who initiated antiretroviral therapy (ART) after Option B+ in Ethiopia. METHODS: A systematic search of literature from PubMed, Hinari, African Journals Online (AJOL), Science Direct, and Google Scholar databases was conducted from June 11, 2013 to August 1, 2023. The authors used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to guide the article selection process and reporting. Observational studies that reported the magnitude and/or risk factors on MTCT of HIV among mother-infant pairs who initiated ART after the implementation of Option B+ in Ethiopia were included. We applied a random-effect model meta-analysis to estimate the overall pooled magnitude and risk factors of MTCT of HIV. A funnel plot and Egger's regression test were employed to check publication bias, and heterogeneity was assessed using I2 statistics. The protocol was registered in the PROSPERO database with registration ID number CRD42022325938. RESULT: Eighteen published articles on the magnitude of MTCT and 16 published articles on its risk factors were included in this review. The pooled magnitude of MTCT of HIV after the Option B+ program in Ethiopia was 4.05% (95% CI 3.09, 5.01). Mothers who delivered their infants at home [OR: 9.74; (95% CI: 6.89-13.77)], had not been on ART intervention [OR: 19.39; (95% CI: 3.91-96.18)], had poor adherence to ART [OR: 7.47; (95% CI: 3.40-16.45)], initiated ART during pregnancy [OR: 5.09; (95% CI: 1.73-14.97)], had WHO clinical stage 2 and above [OR: 4.95; (95% CI: 1.65-14.88]], had a CD4 count below 350 at enrolment [OR: 5.78; (95% CI: 1.97-16.98], had no or low male partner involvement [OR: 5.92; (95% CI: 3.61-9.71]] and whose partner was not on ART [OR: 8.08; (95% CI: 3.27-19.93]] had higher odds of transmitting HIV to their infants than their counterparts. CONCLUSION: This review showed that the pooled magnitude of MTCT of HIV among mother-infant pairs who initiated ART after the Option B + program in Ethiopia is at the desired target of the WHO, which is less than 5% in breastfeeding women. Home delivery, lack of male partner involvement, advanced HIV-related disease, lack of PMTCT intervention, and poor ARV adherence were significant risk factors for MTCT of HIV in Ethiopia.

Rapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021.

BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

Effect of Dolutegravir-Based First-Line Antiretroviral Therapy on Mother-to-Child Transmission of HIV Among HIV-Exposed Infants in Ethiopia: a Before-and-After Study.

Background: Currently, Dolutegravir (DTG)-based regimens are administered to women on Option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among HIV-exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown. Objective: This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among HIV-exposed infants in Ethiopia. Methods: An uncontrolled before-and-after study design was conducted among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevention of mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed, and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with a 95% confidence interval (CI) was calculated to assess the predictor variables. Results: Mothers on DTG-based regimens were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on EFV-based regimens. In addition, poor or fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3) and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor. Conclusion: Mother-to-child transmission of HIV was less frequently observed in mother-infant pairs exposed to the DTG-based regimens as compared to those exposed to the EFV-based regimens. Thus, DTG-based first-line ART regimens supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.

Challenges and lessons learnt in the management of an HIV-exposed neonate with gastroschisis in a resource-limited setting: case report.

Introduction and importance: The incidence of congenital abdominal wall defects is increasing, but few cases have been reported in the African population. Case presentation: The authors report a case of gastroschisis in a term neonate who was delivered through spontaneous vaginal delivery (SVD) in a remote health facility before transfer to a tertiary hospital in Uganda. Although there was no environmental exposure to teratogens, the major risk factor of Gastroschisis, the neonate was low birth weight, HIV-exposed, and the mother had not received folic acid supplementation during the first trimester, known risk factors of gastroschisis. Physical examination revealed intrauterine growth restriction in addition to the findings of the abdominal wall defect. Clinical discussion: There were many missed opportunities in the management of this case which was marred by delayed essential care of the newborn, delayed surgical repair, and transfer to the tertiary surgical centre. At the tertiary surgical centre, a modified silo technique with delayed secondary closure was used to repair the defect, but the neonate still met its death before completing day 7 of life. Conclusion: This case of gastroschisis shows how the diagnosis and management of neonates born with major congenital structural abnormalities in resource-limited settings is still desirable due to lack of sophisticated medical care services to assist in early detection during pregnancy and early surgical intervention at birth to prevent associated mortality. The authors discuss the lessons learnt and provide recommendations for improvement in the care of neonates born with abdominal wall defects and other congenital birth defects.

Outcome of HIV exposed infants towards prevention of mother to child transmission (PMTCT) program and its associated factors in selected health facilities of Addis Ababa, Ethiopia, 2020. Retrospective cross sectional study.

BACKGROUND: Globally, an estimated 36.9 million (31.1-43.9 million) people were living with HIV in 2017, of whom 17.8 million were women and 1.8 million (1.3-2.4 million) children under 15 years of age. Ethiopia has developed an HIV/AIDS prevention, care, and treatment strategic plan in an investment case approach that has been implemented from 2015 to 2020. The study aim was to assess the outcome and risk factors for HIV-exposed infants receiving Prevention of Mother to Child Transmission (PMTCT) follow-up. METHOD: A cross-sectional retrospective study was done. All HIV-exposed infants who were on follow-up in the ART and (PMTCT) clinics of St Paul's Hospital Millennium Medical College, Yekatit 12 Hospital Medical College, and Selam Health Center beginning from September 2016 to January 2019 were included. Data collection was done using a well-designed questionnaire and a review of mothers' and infants' medical record charts and HMIS log book. Descriptive and logistic regression analysis was performed to assess the association between dependent and independent variables. Differences are considered statistically significant at p < 0.05, and their strength is presented using an odds ratio and 95% confidence interval. RESULT: Among the 302 enrolled HIV-exposed infants, 27 (8.9%) were diagnosed as HIV positive. Maternal ART initiation during labor and delivery (AOR = 3.468, 95% CI: 1.22, 13.34, p = 0.04), frequent hospital admission of the infant (AOR = 17.49, 95% CI: 5.41, 56.2, p = 0.001), and mixed feeding option (AOR = 8.25, 95% CI: 2.212, 30.77, p = 0.02) were the major factors associated with positive HIV serostatus among HIV-exposed infants. CONCLUSION: and Recommendation: The level of HIV infection among infants born to HIV-positive mothers is high as compared to the national and WHO goals. Exclusive breastfeeding should be advocated for all HIV-exposed infants, especially in resource-limited settings like Ethiopia due to the increased prevalence of diarrheal illness.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24 months of life in Western Kenya.

BACKGROUND: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. METHODS: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. RESULTS: Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. CONCLUSIONS: Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants.

HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using 1H-NMR spectroscopy on maternal plasma at 28 weeks' gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants' plasma metabolites involved in energy utilization, growth, and protection from infection.

Process Evaluation of Services for HIV-Infected Post-Partum Women and HIV-Exposed Infants in Primary Health Care Blantyre Malawi.

HIV testing among HIV-exposed infants (HEI) in Malawi is below global targets and, affected by low utilisation of health services after birth. We conducted a mixed methods evaluation of the implementation of services for early infant diagnosis (EID) of HIV against national guidelines in Blantyre, Malawi, to inform the development of strategies to improve EID services uptake. We estimated coverage of HEI enrolment in HIV care and HIV testing at 6 weeks through a retrospective data review. We qualitatively explored implementation gaps in EID services through process mapping of 8 mother-infant pairs (MIP); and investigated healthcare workers' (HCW) perspectives on the implementation gaps through group interviews with 16 HCWs. We analysed the quantitative data descriptively and conducted a thematic content analysis of qualitative data. Of 163 HEIs born at the study sites, 39 (24%) were enrolled in an HIV care clinic before post-natal discharge, and 85 (52%) received HIV testing by 6 weeks. The median time for MIP to receive EID services was 4 (1-8) hours. The implementation gaps observed during process mapping included: failure to identify and enrol HEI in HIV care clinic; lack of immunisation, counselling for HEI testing, HIV testing, drug refilling, and family planning; and different appointment dates for mother and infant. HCWs reported delays and gaps influencing optimal service provision including: lack of screening to identify MIP, limited supervision for student HCWs when providing services, inadequate capacity of point of care machines, challenges with integrating services, and role confusion. Use of unique identifiers for MIP and establishing a booking system to schedule appointments to suit point of care machine capacity were primary service improvement recommendations. This study identified suboptimal EID services in Malawi due to process, capacity, and system factors. Context-appropriate interventions accommodating systems thinking are needed to enhance service provision.

Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.

Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.

Attention and neurodevelopment in young children who are HIV-exposed uninfected.

ABSTRACTChildren HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment.

A scoping review on HIV early infant diagnosis among HIV exposed infants, ART use and adherence in Tanzania.

BACKGROUND: HIV Early Infant Diagnosis (HEID) is critical for the timely initiation of HIV treatments and improved health outcomes among HIV-infected infants. However, the uptake of HEID remains largely low in Tanzania. This descriptive scoping review of evidence on HEID among HIV-exposed infants in Tanzania seeks to understand the dynamics of HEID, ART use and adherence to inform targeted interventions and promote its uptake. METHODS: The Arksey and O'Malley's methodological framework guided this scoping review. We searched for peer-published articles on HEID in Tanzania through PubMed and Google Scholar with full-text retrieval from HINAR. We included only English language articles published between 2013 and 2022. Further searches for the materials on the reference lists of the publications yielded additional relevant articles. We carried out an inductive thematic analysis to analyze and synthesize the data. RESULTS: In all, nine articles met the inclusion criteria and, hence, qualified for the review. The variations in the uptake of HEID in the empirical literature reviewed indicate an upward trend. HEID increased from 77.2% in 2009 to 97.8% in 2011 in Kilimanjaro, Mbeya and Tanga and from 53.2% in 2014 to 69.2% in 2016 in Dar es Salaam. The median age at the initial test ranged from 5.6 weeks in Kilimanjaro to 8.6 weeks in Mbeya. The uptake of HEID was necessitated by individual, household and health facility factors. Unknown HIV status at conception, low level of education of the household head, and large household size negatively affected uptake of HEID. The health facility factors such as unavailability of the test kits, long distances to the facility and transport costs negatively influenced HEID uptake. The percentage of HIV-positive infants on ART ranged from 52.7 to 61%, and loss to follow ranged from 31 to 61%. CONCLUSION: The uptake of HEID varied among regions depending on individual, household and health facility factors. Multifaced efforts are needed to address these factors for accelerated uptake of HEID and improved health outcomes and survival among this strategic population group.

Neurodevelopment of children who are HIV-exposed and uninfected in Kenya.

INTRODUCTION: Predictors of neurodevelopment among children who are HIV-exposed uninfected (CHEU) are poorly understood. METHODS: Mothers with and without HIV and their children were enrolled during 6-week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1-year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site. RESULTS: At 1-year evaluation, CHEU (n = 709) and children who are HIV-unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate-to-severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: -1.38, 95% CI: -2.05, -0.71), food insecurity was associated with lower social scores (adjusted coeff: -0.37, 95% CI: -0.73, -0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: -0.76, 95% CI: -1.40, -0.13) and gross motor scores (adjusted coeff: -1.07, 95% CI: -1.81, -0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: -0.51, 95% CI: -1.01, -0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: -0.45, 95% CI: -0.87, -0.03) or a deceased or absent father (adjusted coeff: -0.81, 95% CI: -1.58, -0.05), respectively. CONCLUSIONS: Biologic and social factors were associated with child neurodevelopment. Despite socio-demographic differences between CHEU and CHUU, 1-year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.

Strengthening the evidence to improve health outcomes of children with perinatal HIV exposure.

INTRODUCTION: The number of children exposed to HIV and possibly to antiretroviral therapy (ART) in utero and during breastfeeding and are uninfected (HEU) globally will continue to increase from the estimated 15.9 million in 2021. DISCUSSION: There are still significant gaps in our understanding of the impact of HIV and/or ART exposure in children who are HEU, in terms of prevalence/incidence and severity on health and wellbeing, and long after exposure has ended. While there have been substantial programmatic efforts to support the elimination of vertical transmission of HIV, additional rigorous research is needed to better understand the biological, (psycho)social and structural factors contributing to optimal health for populations who are HEU. Furthermore, the best approaches to address and study the gaps in understanding also need to be explored. Given the scope of the problem including the large numbers of affected people as well as the often limited and competing in-country resources for populations affected by HIV, novel methodologies, including multi-level approaches and advanced analytics, need to be considered. CONCLUSIONS: A growing population of children who are HEU are maturing into adolescence and young adulthood. Research to advance understanding of the possible negative long-term effects of HIV and/or ART exposure in these youth is supported by the US National Institutes of Health. Both large epidemiological studies and smaller more comprehensive cohort studies may be required to address the complexity of the issue. Integrating both types of studies could allow the establishment of more reliable and validated predictions of which youth who are HEU are at the highest risk for specific negative health outcomes, such as mental health and neurocognitive disorders, and which interventional approaches may be most successful to address specific deficits both in terms of prevention and treatment. Finally, these goals can be more rapidly achieved with data science efforts, data harmonisation between studies and with sustainable data-sharing practices. It is important to expand the commitment to research to identify biological, social and structural drivers, to develop screening tools, and impactful and contextually appropriate interventions to address the health and wellbeing of children who are HEU from birth through adulthood.

Neurodevelopment among children exposed to HIV and uninfected in sub-Saharan Africa.

INTRODUCTION: The population of 16 million children exposed to HIV and uninfected (CHEU) under 15 years of age continues to expand rapidly, and the estimated prevalence of CHEU exceeds 20% in several countries in sub-Saharan Africa with high HIV prevalence. Some evidence suggests that CHEU experience suboptimal neurodevelopmental outcomes compared to children born to women without HIV. In this commentary, we discuss the latest research on biologic and socio-behavioural factors associated with neurodevelopmental outcomes among CHEU. DISCUSSION: Some but not all studies have noted that CHEU are at risk of poorer neurodevelopment across multiple cognitive domains, most notably in language and motor skills, in diverse settings, ages and using varied assessment tools. Foetal HIV exposure can adversely influence infant immune function, structural brain integrity and growth trajectories. Foetal exposure to antiretrovirals may also influence outcomes. Moreover, general, non-CHEU-specific risk factors for poor neurodevelopment, such as preterm birth, food insecurity, growth faltering and household violence, are amplified among CHEU; addressing these factors will require multi-factorial solutions. There is a need for rigorous harmonised approaches to identify children at the highest risk of delay. In high-burden HIV settings, existing maternal child health programmes serving the general population could adopt structured early child development programmes that educate healthcare workers on CHEU-specific risk factors and train them to conduct rapid neurodevelopmental screening tests. Community-based interventions targeting parent knowledge of optimal caregiving practices have shown to be successful in improving neurodevelopmental outcomes in children and should be adapted for CHEU. CONCLUSIONS: CHEU in sub-Saharan Africa have biologic and socio-behavioural factors that may influence their neurodevelopment, brain maturation, immune system and overall health and wellbeing. Multidisciplinary research is needed to disentangle complex interactions between contributing factors. Common environmental and social risk factors for suboptimal neurodevelopment in the general population are disproportionately magnified within the CHEU population, and it is, therefore, important to draw on existing knowledge when considering the socio-behavioural pathways through which HIV exposure could impact CHEU neurodevelopment. Approaches to identify children at greatest risk for poor outcomes and multisectoral interventions are needed to ensure optimal outcomes for CHEU in sub-Saharan Africa.

Lower academic performance among children with perinatal HIV exposure in Botswana.

INTRODUCTION: Studies have reported a higher risk of suboptimal neurodevelopment among children who are HIV-exposed uninfected (HEU) compared to children HIV-unexposed uninfected (HUU). Actual academic performance among school-aged children by HIV exposure status has not been studied. METHODS: Academic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana-based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran-Mantel-Haenszel test. Lower academic performance was defined as a grade of "C" or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance. RESULTS: Between April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9-10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three-drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]). CONCLUSIONS: In this Botswana-based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio-demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.