Effectiveness and Safety of Tenofovir Alafenamide Fumarate in the Prevention of Perinatal Hepatitis B Transmission: A Meta-Analysis.

AIM: This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterations in levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine ß2-microglobulin (ß2-M) in mothers. RESULTS: An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6 months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or ß2-M levels. CONCLUSIONS: TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.

Factors associated with knowledge of mother-to-child transmission of HIV among reproductive-age women in Indonesia: a multilevel analysis.

BACKGROUND: Maternal transmission of human immunodeficiency virus (HIV) commonly occurs from mother to child during pregnancy, delivery, and breastfeeding which accounts for almost all the new HIV infections among children aged 0-14 years. Despite major efforts and progress in controlling and preventing HIV, it continues to pose a great public health threat, especially in Indonesia. This study assessed the factors associated with the knowledge of mother-to-child transmission (MTCT) of HIV among reproductive-age women in Indonesia. METHODS: This study used data from the 2017 Indonesian Demographic and Health Survey (IDHS). We sampled 39,735 reproductive-age women (15-49 years) for analysis. Using Stata version 16.0, multilevel logistic regression models were fitted, and the results were presented as adjusted odds ratios (aORs) with their confidence intervals (CIs). RESULTS: The study found that 72% of women had knowledge of MTCT of HIV. Women who were aged between 45 and 49 years (aOR = 1.65, 95%CI = 1.46-1.88) had higher odds of knowledge of MTCT of HIV than those aged 15-19 years. Women who attained higher education (aOR = 2.92, 95%CI = 2.06-4.15) had increased odds of knowledge of MTCT of HIV than those with no formal education. Women who had four children (aOR = 1.19, 95% CI = 1.05-1.35) had higher odds of knowledge of MTCT of HIV than nulliparous women. Women who frequently read newspapers/magazines (aOR = 1.14, 95%CI = 1.06-1.25) and frequently used the internet almost every day (aOR = 1.28, 95%CI = 1.19-1.38) had higher odds of knowledge of MTCT of HIV than those who did not read newspapers/magazines and non-users of internet, respectively. Women within the richer (aOR = 1.11, 95%CI = 1.02-1.20) and the richest (aOR = 1.14, 95%CI = 1.04-1.25) wealth quintile higher odds of knowledge of MTCT of HIV than those in the poorest wealth quantile. Women who resided in rural areas were less likely to have knowledge of MTCT of HIV (aOR = 0.79, 95% CI = 0.74-0.86) than those in urban settlements. CONCLUSIONS: Knowledge of MTCT of HIV was slightly above average. The study findings on the factors associated with knowledge of MTCT of HIV provide evidence for policymakers and clinicians to utilize in the quest to eliminate MTCT of HIV among children. We recommend that awareness programs should consider the key findings from this study when delivering public education or when developing interventions to improve women's knowledge on MTCT of HIV.

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.

Vertical HIV-1 Transmission in the Setting of Maternal Broad and Potent Antibody Responses.

Despite the worldwide availability of antiretroviral therapy (ART), approximately 150,000 pediatric HIV infections continue to occur annually. ART can dramatically reduce HIV mother-to-child transmission (MTCT), but inconsistent drug access and adherence, as well as primary maternal HIV infection during pregnancy and lactation are major barriers to eliminating vertical HIV transmission. Thus, immunologic strategies to prevent MTCT, such as an HIV vaccine, will be required to attain an HIV-free generation. A primary goal of HIV vaccine research has been to elicit broadly neutralizing antibodies (bnAbs) given the ability of passive bnAb immunization to protect against sensitive strains, yet we previously observed that HIV-transmitting mothers have more plasma neutralization breadth than nontransmitting mothers. Additionally, we have identified infant transmitted/founder (T/F) viruses that escape maternal bnAb responses. In this study, we examine a cohort of postpartum HIV-transmitting women with neutralization breadth to determine if certain maternal bnAb specificities drive the selection of infant T/F viruses. Using HIV pseudoviruses that are resistant to neutralizing antibodies targeting common bnAb epitopes, we mapped the plasma bnAb specificities of this cohort. Significantly more transmitting women with plasma bnAb activity had a mappable plasma bnAb specificity (six of seven, or 85.7%) compared to that of nontransmitting women with plasma bnAb activity (7 of 21, or 33.3%, P = 0.029 by 2-sided Fisher exact test). Our study suggests that having multispecific broad activity and/or uncommon epitope-specific bnAbs in plasma may be associated with protection against the vertical HIV transmission in the setting of maternal bnAb responses. IMPORTANCE As mother to child transmission (MTCT) of HIV plays a major part in the persistence of the HIV/AIDS epidemic and bnAb-based passive and active vaccines are a primary strategy for HIV prevention, research in this field is of great importance. While previous MTCT research has investigated the neutralizing antibody activity of HIV-infected women, this is, to our knowledge, the largest study identifying differences in bnAb specificity of maternal plasma between transmitting and nontransmitting women. Here, we show that among HIV-infected women with broad and potent neutralization activity, more postpartum-transmitting women had a mappable plasma broadly neutralizing antibody (bnAb) specificity, compared to that of nontransmitting women, suggesting that the nontransmitting women more often have multispecific bnAb responses or bnAb responses that target uncommon epitopes. Such responses may be required for protection against vertical HIV transmission in the setting of maternal bnAb responses.

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

INTRODUCTION: Two 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. METHOD: A 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. RESULTS: A 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). CONCLUSION: The 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.

Positivity rate, trend and associated risk factors of mother-to-child transmission of HIV among HIV-exposed infants.

BACKGROUND: Mother-To-Child-Transmission (MTCT) of Human Immunodeficiency Virus (HIV) occurs during pregnancy, delivery and breastfeeding, and cause infection among several new-borns. However, there is limited recent evidence on the burden of MTCT of HIV in Ethiopia from a large-scale data. Thus, this study aimed to determine the positivity rate, trend and associated risk factors of MTCT among HIV-exposed infants. METHODOLOGY: A cross-sectional study was conducted among 5,679 infants whose specimen referred to Ethiopian Public Health Institute HIV referral laboratory for Early Infant Diagnosis (EID) from January 01, 2016, to December 31, 2020. Data were extracted from the national EID database. Frequencies and percentages were used to summarize the data on characteristics of infants. Logistic regression analysis was employed to identify factors associated with positivity rate of MTCT of HIV. Level of significance was set at 5%. RESULTS: The mean age of the infants was 12.6 (± 14.6) weeks with an age range of 4 to 72 weeks. Half of the infants (51.4%) were female. The positivity rate of MTCT decreased from 2.9% in 2016 to 0.9% in 2020 with five-year average positivity rate of 2.6%. HIV test after six weeks (Adjusted odds ratio (AOR) = 2.7; 95% confidence interval (CI): (1.8-4.0,)); p < 0.001), absence of prevention of mother-to-child-transmission (PMTCT) service (AOR = 4.6; 95% CI: (2.9-7.4)); p = 0.001), nevirapine prophylaxis not received (AOR = 2.0; 95% CI: (1.3-3.2)); p < 0.001), and unknown ART status of the mother at delivery (AOR = 11; 95% CI: (5.5-22.1)); p < 0.001) were significantly associated with MTCT of HIV. CONCLUSION: The positivity rate of MTCT of HIV was showing declining tendency gradually in the study period. Strengthening PMTCT service, early HIV screening and starting ART for pregnant women, and early infant diagnosis are required to reduce the burden of HIV infection among infants exposed to HIV.

Early infant diagnosis of HIV infection: a mixed-method study of uptake and challenges at primary health centers in Lagos State, Nigeria.

INTRODUCTION: Nigeria has a low uptake of early infant diagnosis (EID) of HIV despite its high pediatric HIV infection rate. Efforts to increase the EID of HIV have been limited by many factors. This research assessed EID uptake and challenges service providers experienced in providing routine care for HIV-exposed infants. METHODS: This is a mixed-method study at primary health centers (PHCs) in Lagos state, Nigeria. The quantitative component of the research was a review of the PMTCT Infant Follow-up Register at a purposive sample of 22 PHCs of Lagos State. The number of HIV-exposed infants (HEIs) returned for a dried blood sample (DBS) collection, date of collection, and the infant's EID results for one year preceding the study were captured on Research Electronic Data Capture (RedCap). In-depth interviews were conducted with service providers purposively selected per participating PHC. Electronic transcripts were analyzed using MAXQDA 2020 (VERBI Software, 2019). RESULTS: Twenty-two Lagos State primary health centers participated in the research. Fifteen PHCs (68.2%) had PMTCT HIV counseling and Infant follow-up registers. Documentation of DBS sample collection was observed in 12 (54.6%) PHCs. Both DBS sample collection and EID results documentation were observed in only nine (40.9%) PHCs. In-depth interviews revealed both maternal and health systems' challenges to EID. The denial of HIV status was the only maternal factor reported as a barrier against the use of EID services. Health systems challenges include unavailability of EID services, uncertainty regarding whether EID is performed in a facility, referral to secondary health facilities for EID services (leading to losses to follow-up), and delay in getting results of EID. Task-shifting of DBS collection by nurses was suggested as means to increase access to EID services. CONCLUSIONS: There is a need to expand EID services and address women's denial of HIV infection. Counseling women and linkage to available services are emphasized. Re-training of health workers on DBS collection and proper documentation of EID services were noted as key to improving the implementation of early infant diagnosis of HIV in the state.

Prenatal ultrasound screening and pregnancy outcomes in HIV-positive women in Germany: results from a retrospective single-center study at the Charité-Universitätsmedizin Berlin.

OBJECTIVES: The aim of this study was to investigate the rate of Mother-to-child-transmission (MTCT) in women living with HIV (WLWH) in a tertiary care institution. Furthermore, we aimed to assess prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection." METHODS: In this single-center study, retrospective data related to pregnancy and childbirth were collected from 420 WLWH. All data were evaluated descriptively. RESULTS: From January 2014 to December 2020, a total number of 420 pregnant WLWH delivered 428 newborns. 415 (98.8%) were receiving antiretroviral therapy (ART) and 88.8% had a viral load of < 50 cop/ml prior delivery. 46 (11%) of the newborns were born prematurely. Low birth weight < 2500 g occurred in 38 (9.1%) of the children. 219 (52.1%) caesarean sections (CS) were performed. The most frequent indication for an elective CS was a previous CS (70.2%). 8 severe malformations were detected using first and second trimester ultrasound. In one child, MTCT was detected postpartum, resulting in an HIV transmission rate of 0.2% in the presented cohort. CONCLUSIONS: The low rate of vertical HIV-transmission in our cohort of 0.2% is the result of interdisciplinary prenatal care and high experience of healthcare providers in treatment of WLWH. Despite high ART coverage and adherence, good maternal immune system and very low vertical HIV transmission rate, maternal HIV infection remains a challenge in obstetric care. First and second ultrasound screening should be a part of prenatal care for HIV-infected women and should also be offered to HIV-negative women. A reduction of the rate of unnecessary elective caesarean deliveries in WLWH is necessary to reduce complications in subsequent pregnancies.

The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus.

BACKGROUND: Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. METHODS: Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. RESULTS: Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68-1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77-1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49-1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). CONCLUSIONS: Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. CLINICAL TRIALS REGISTRATION: NCT00825929.

Community-based progress indicators for prevention of mother-to-child transmission and mortality rates in HIV-exposed children in rural Mozambique.

BACKGROUND: Eliminating mother-to-child HIV-transmission (EMTCT) implies a case rate target of new pediatric HIV-infections< 50/100,000 live-births and a transmission rate < 5%. We assessed these indicators at community-level in Mozambique, where MTCT is the second highest globally.. METHODS: A cross-sectional household survey was conducted within the Manhiça Health Demographic Surveillance System in Mozambique (October 2017-April 2018). Live births in the previous 4 years were randomly selected, and mother/child HIV-status was ascertained through documentation or age-appropriate testing. Estimates on prevalence and transmission were adjusted by multiple imputation chained equation (MICE) for participants with missing HIV-status. Retrospective cumulative mortality rate and risk factors were estimate by Fine-Gray model. RESULTS: Among 5000 selected mother-child pairs, 3486 consented participate. Community HIV-prevalence estimate in mothers after MICE adjustment was 37.6% (95%CI:35.8-39.4%). Estimates doubled in adolescents aged < 19 years (from 8.0 to 19.1%) and increased 1.5-times in mothers aged < 25 years. Overall adjusted vertical HIV-transmission at the time of the study were 4.4% (95% CI:3.1-5.7%) in HIV-exposed children (HEC). Pediatric case rate-infection was estimated at 1654/100,000 live-births. Testing coverage in HEC was close to 96.0%; however, only 69.1% of them were tested early(< 2 months of age). Cumulative child mortality rate was 41.6/1000 live-births. HIV-positive status and later birth order were significantly associated with death. Neonatal complications, HIV and pneumonia were main pediatric causes of death. CONCLUSIONS: In Mozambique, SPECTRUM modeling estimated 15% MTCT, higher than our district-level community-based estimates of MTCT among HIV-exposed children. Community-based subnational assessments of progress towards EMTCT are needed to complement clinic-based and modeling estimates.

Relationships Between Maternal Antibody Responses and Early Childhood Infection With Kaposi Sarcoma-Associated Herpesvirus.

While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.4%) mothers were found to be KSHV seropositive. Longitudinal KSHV titers were fairly stable over time, although seroreversion was still common. Of the total 124 mothers, 81 had at least 1 child KSHV seroconvert during the 2 years analyzed, while the remaining 43 mothers had KSHV-seronegative children. Mothers of KSHV-negative children had higher geometric mean titers than mothers of KSHV-positive children; however, there was no difference in the presence of neutralizing antibodies. This suggests that a strong anti-KSHV immune response, and potentially nonneutralizing antibodies, may reduce transmission.

Mother-to-child HIV transmission and its correlates in India: systematic review and meta-analysis.

BACKGROUND: In India, preventing mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) remains one of the foremost challenge in community health. Countrywide MTCT of HIV is estimated to be > 10,000 annually. Aims of present study are to find out the prevalence of HIV and correlates of HIV transmission among children given birth by HIV infected mother through systematic review along with meta-analysis. METHODS: All avaiable articles are retrieved using MEDLINE, Cochrane Library, Science Direct, EMBASE, Google Scholar and PUBMED following guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) are applied to critically reviewing the selected articles. STATA 13.0 is used to preparation of forest plot for Meta-analysis. For assessment of heterogeneity and publication biases I2 statistics along with Begg and Mazumdar's test and Egger's tests are used. Odds ratio (OR) along with forest plots have been showing with 95% confidence interval (CI). RESULTS: All together 10 studies including 1537 pairs of mothers and new births are assessed in present meta-analysis. Present analysis revealed the prevalence of HIV due to MTCT in India as 8.76% (95% CI; 5.76, 12.31). Analysis of subgroups exhibit a higher pooled prevalence in eastern region of India, 10.83% (95% CI: 5.9, 17.81) and lower in in Western region in India, 6.37% (95% CI: 4.65, 8.49). Status of MTCT before and after initiation of universal ART are 10.23% (95% CI 6.61, 14.55) and 7.93% (95% CI 4.18, 12.76) respectively. Associated factors with MTCT of HIV include absence of maternal prevention of MTCT intervention, OR = 10.82 (95% CI: 5.28, 22.17), lacking in administration of infant ARV (antiretroviral), OR = 8.21 (95% CI: 4.82, 14.0) and absence of medical facility during childbirth OR = 3.73 (95% CI: 1.67, 8.33). CONCLUSIONS: In India, pooled HIV prevalence of MTCT as high as 8.78% (95% CI; 5.76, 12.31) among babies born to infected mothers warrants urgent need of focused intervention for providing ART (PMTCT intervention), ensuring proper infant ARV prophylaxis, and avoiding delivery without proper medical facility to pregnant women with HIV for reduction of occurrence in HIV transmission from mothers to children.

Impact of refugee influx on the epidemiology of late-presenting HIV-infected pregnant women and mother-to-child transmission: comparing a southern and northern medical centre in Germany.

PURPOSE: Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. METHODS: Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010-2012) and B (2013-2015). RESULTS: In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. CONCLUSIONS: HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.

Protocol for the evaluation of the population-level impact of Zimbabwe's prevention of mother-to-child HIV transmission program option B+: a community based serial cross-sectional study.

BACKGROUND: WHO recommends that HIV infected women receive antiretroviral therapy (ART) minimally during pregnancy and breastfeeding ("Option B"), or ideally throughout their lives regardless of clinical stage ("Option B+") (Coovadia et al., Lancet 379:221-228, 2012). Although these recommendations were based on clinical trials demonstrating the efficacy of ART during pregnancy and breastfeeding, the population-level effectiveness of Option B+ is unknown, as are retention on ART beyond the immediate post-partum period, and the relative impact and cost-effectiveness of Option B+ compared to Option A (Centers for Disease Control and Prevention, Morb Mortal Wkly Rep 62:148-151, 2013; Ahmed et al., Curr Opin HIV AIDS 8:473-488, 2013). To address these issues, we conducted an impact evaluation of Zimbabwe's prevention of mother to child transmission programme conducted between 2011 and 2018 using serial, community-based cross-sectional serosurveys, which spanned changes in WHO recommendations. Here we describe the rationale for the design and analysis. METHODS/DESIGN: Our method is to survey mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. We collect questionnaires, blood samples from mothers and babies for HIV antibody and viral load testing, and verbal autopsies for deceased mothers/babies. Using this approach, we collected data from two previous time points: 2012 (pre-Option A standard of care), 2014 (post-Option A / pre-Option B+) and will collect a third round of data in 2017-18 (post Option B+ implementation) to monitor population-level trends in mother-to-child transmission of HIV (MTCT) and HIV-free infant survival. In addition, we will collect detailed information on facility level factors that may influence service delivery and costs. DISCUSSION: Although the efficacy of antiretroviral therapy (ART) during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (PMTCT) has been well-documented in randomized trials, little evidence exists on the population-level impact and cost-effectiveness of Option B+ or the influence of the facility on implementation (Siegfried et al., Cochrane Libr 7:CD003510, 2017). This study will provide essential data on these gaps and will provide estimates on retention in care among Option B+ clients after the breastfeeding period. TRIAL REGISTRATION: NCT03388398 Retrospectively registered January 3, 2018.

[12-months efficacy of option B+ for prevention of mother-to-child transmission of HIV in Yaoundé, Cameroon]. / Efficacité à 12 mois de l'option B+ pour prévenir la transmission mère-enfant (PTME) du VIH à Yaoundé, Cameroun.

BACKGROUND: Cameroon has adopted the option B+ for the prevention of mother-to-child transmission (MTCT) program of HIV in August 2014 in order to eradicate MTCT of HIV. OBJECTIVE: To analyze in routine life settings, efficacy of option B+ for PMTCT and associate factors. METHODS: We conducted a cross-sectional study over a 6-month period in the ESSOS hospital center. Study population comprised HIV-positive mothers and their infants aged 0-24 months. Variables included were : moment of HIV maternal testing, timing of commencement of maternal antiretroviral therapy (ART) and self-reported adherence to ART. Efficacy was measured through early and late MTCT rate and associated factors. RESULTS: We included 200 mothers and 124 infants. Under option B+, the rate of transmission was at 4.20% at 6 weeks and 5.83% at 12 months. The rate of HIV transmission in breastfed infants stood at 3.7%. In unadjusted analysis, bottle-feeding, term at birth, early screening and management during pregnancy were associated with lower risk of HIV transmission. After adjustment, term at delivery after 37 weeks adjusted odds ratio (AOR) [0.059; (0.0061; 0.56)] was protective; while lack of prophylaxis was among HIV-exposed infants emerged as the main factor associated with residual transmission of HIV [AOR 117.23 ; (3.55 ; 3874.9)]. CONCLUSION: In this setting of Yaoundé, routine option B+ posted laudable results at 12 months even amongst breastfed children and should therefore be made sustainable.

Mother-to-Child Transmission of HIV and HIV-Free Survival in Swaziland: A Community-Based Household Survey.

In Swaziland, no data are available on the rates of HIV infection and HIV-free survival among children at the end of the breastfeeding period. We performed a national crosssectional community survey of children born 18-24 months prior to the study, in randomly selected constituencies in all 4 administrative regions of Swaziland, from April to June 2015. Mother-to-child transmission (MTCT) of HIV and HIV-free survival rates were calculated for all HIV-exposed children. The overall HIV-free survival rate at 18-24 months was 95.9% (95% CI 94.1-97.2). The estimated proportion of HIV infected children among known HIV-exposed children was 3.6% (95% CI 2.4-5.2). Older maternal age, delivering at a health facility, and receiving antenatal antiretroviral drugs were independently associated with reduced risk for child infection or death. The Swaziland program for prevention of MTCT achieved high HIV-free survival (95.9%) and low MTCT (3.6%) rates at 18-24 months of age when Option A (infant prophylaxis) of the WHO 2010 guidelines was implemented.

Mother-to-child transmission of HIV infection and its associated factors in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Mother-to-child transmission (MTCT) is the main mode of HIV transmission in children under 15 years old. This problem is significant in the Sub-Saharan African countries, where more than 80% of children living with HIV are found. Previous studies in Ethiopia present inconsistent and inconclusive findings on the prevalence and associated factors of MTCT of HIV. Therefore, this study was conducted to determine the pooled prevalence of MTCT of HIV and its associated factors in Ethiopia. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. All published studies were retrieved using relevant search terms in MEDLINE, PUBMED, Cochrane Library, EMBASE, Google Scholar, CINAHL, and African Journals Online databases. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to critically appraise articles. STATA version 14 software was used to perform the Meta-analysis. The I2 statistics was used to test heterogeneity and publication bias was assessed using Begg's and Egger's tests. Odds ratio (OR) with 95% confidence interval (CI) was presented using forest plots. RESULTS: A total of nine studies, 3688 mother-baby pairs, were included in this meta-analysis. The pooled prevalence of MTCT of HIV in Ethiopia was 9.93% (95% CI: 7.29, 12.56). The subgroup analysis showed a higher prevalence of MTCT of HIV in Dire Dawa City Administration (15.7%) and lowest in Southern Nations, Nationality and Peoples Region (SNNPR) (4.16%). Associated factors with MTCT of HIV include: mixed feeding, OR = 7.46 (95%CI: 4.71, 11.81), absence of infant ARV prophylaxis, OR = 7.89 (95%CI: 4.32, 14.42), home delivery, OR = 5.08 (95%CI: 2.32, 11.15), and absence of maternal PMTCT intervention, OR = 7.13 (95% CI: 3.31, 15.35). CONCLUSIONS: Almost one in ten HIV exposed infants become HIV positive in Ethiopia. Factors like: mixed feeding, the absence of infant ARV prophylaxis, home delivery and absence of mother's PMTCT intervention were significantly associated with MTCT of HIV. Therefore, the governmental and non-governmental organizations need to focus on the identified factors and work towards improving the prevention of mother to child transmission of HIV (PMTCT) program.

Determinants of HIV infection among children born to mothers on prevention of mother to child transmission program of HIV in Addis Ababa, Ethiopia: a case control study.

BACKGROUND: Despite wide spread use of Antiretroviral Therapy (ART) by pregnant women living with Human Immunodeficiency Virus (HIV), the transmission rate is still higher by 18% after breastfeeding ends. The aim of this study was to identify factors affecting mother-to-child HIV transmission. METHODS: Unmatched case-control study was conducted in Addis Ababa, from April to May, 2017. A case was HIV positive mother who had been on PMTCT program with her child confirmed HIV positive at or before 24 months and control was HIV positive mother who had been on PMTCT program with her child tested definitive HIV negative at 24 months. Accordingly, 44 cases were identified and for each case four controls with the nearest date of birth to the cases were selected from same health facilities. Primary data collected from the mothers were supplemented by record reviews and entered to Epidata version 3.1 and analyzed using SPSS version 22. Multivariate logistic regression was fitted to identify factors independently associated with mother-to-child HIV transmission. RESULTS: Lack of participation in mother-to-mother support program (AOR: 5.1; 95% CI: 1.4, 18.1), low partner involvement (AOR: 6.9; 95% CI: 1.4, 13.4), poor ART adherence (AOR:3.1; 95% CI: 1.3, 7.5), positive syphilis test results (AOR: 3.2; 95% CI: 1.2, 8.6), maternal malnutrition (AOR: 3.1; 95% CI: 1.4, 6.8), unplanned pregnancy (AOR: 10.3; 95% CI: 3.9, 27.2), home delivery (AOR: 5.3; 95% CI: 1.4, 19.4) and mixed feeding of the child during first six months of life (AOR: 12.5; 95% CI: 2.9, 52.7) were significantly associated with MTCT of HIV. CONCLUSIONS: Mother-to-mother support, male partner involvement in PMTCT of HIV, strengthening antenatal care, counseling mothers on appropriate infant feeding options are important to reduce mother -to- child transmission of HIV.

Impact of maternal ART on mother-to-child transmission (MTCT) of HIV at six weeks postpartum in Rwanda.

BACKGROUND: In 2010, Rwanda adopted ART for prevention of mother to child transmission of HIV from pregnant women living with HIV during pregnancy and breasfeeding period. This study examines rates of mother-to-child-transmission of HIV at 6-10 weeks postpartum and risk factors for mother-to-child transmission of HIV (MTCT) among HIV infected women on ART during pregnancy and breastfeeding. METHODS: A cross-sectional survey study was conducted between July 2011-June 2012 among HIV-exposed infants aged 6-10 weeks and their mothers/caregivers. Stratified multi-stage, probability proportional to size and systematic sampling to select a national representative sample of clients. Consenting mothers/caregivers were interviewed on demographic and program interventions. Dry blood spots from HIV-exposed infants were collected for HIV testing using DNA PCR technique. Results are weighted for sample realization. Univariable analysis of socio-demographic and programmatic determinants of early mother-to-child transmission of HIV was conducted. Variables were retained for final multivariable models if they were either at least of marginal significance (p-value < 0.10) or played a confounding role (the variable had a noticeable impact > 10% change on the effect estimate). RESULTS: The study sample was 1639 infants with HIV test results. Twenty-six infants were diagnosed HIV-positive translating to a weighted MTCT estimate of 1.58% (95% CI 1.05-2.37%). Coverage of most elimination of MTCT (EMTCT) program interventions, was above 80, and 90.4% of mother-infant pairs received antiretroviral treatment or prophylaxis. Maternal ART and infant antiretroviral prophylaxis (OR 0.01; 95%CI 0.001-0.17) and maternal age older than 25 years were significantly protective (OR 0.33; 95%CI 0.14-0.78). No disclosure of HIV status, not testing for syphilis during pregnancy and preterm birth were significant risk factors for MTCT. Factors suggesting higher socio-demographic status (flush toilet, mother self-employed) were borderline risk factors for MTCT. CONCLUSION: ART for all women during pregnancy and breastfeeding was associated with the estimated low MTCT rate of 1.58%. Mothers who did not receive a full package of anti-retroviral therapy according to the Rwanda EMTCT protocol, and young and single mothers were at higher risk of MTCT and should be targeted for support in preventing HIV infection.

Feasibility and utility of active case finding of HIV-infected children and adolescents by provider-initiated testing and counselling: evidence from the Laquintinie hospital in Douala, Cameroon.

BACKGROUND: Universal HIV testing and treatment of infected children remain challenging in resource-limited settings (RLS), leading to undiagnosed children/adolescents and limited access to pediatric antiretroviral therapy (ART). Our objective was to evaluate the feasibility of active cases finding of HIV-infected children/adolescents by provider-initiated testing and counseling in a health facility. METHODS: A cross-sectional prospective study was conducted from January through April 2016 at 6 entry-points (inpatient, outpatient, neonatology, immunization/family planning, tuberculosis, day-care units) at the Laquintinie Hospital of Douala (LHD), Cameroon. At each entry-point, following counseling with consenting parents, children/adolescents (0-19 years old) with unknown HIV status were tested using the Rapid Diagnostic Test (RDT) (Determine®) and confirmed with a second RDT (Oraquick®) according to national guidelines. For children less than 18 months, PCR was performed to confirm every positive RDT. Community health workers linked infected participants by accompanying them from the entry-point to the treatment centre for an immediate ART initiation following the « test and treat ¼ strategy. Statistical analysis was performed, with p < 0.05 considered significant. RESULTS: Out of 3439 children seen at entry-points, 2107 had an unknown HIV status (61.3%) and HIV testing acceptance rate was 99.9% (2104). Their mean age was 2.1 (Sd = 2.96) years, with a sex ratio boy/girl of 6/5. HIV prevalence was 2.1% (44), without a significant difference between boys and girls (p = 0.081). High rates of HIV-infection were found among siblings/descendants (22.2%), TB treatment unit attendees (11.4%) and hospitalized children/adolescents (5.6%); p < 0.001. Up to 95.4% (42/44) of those infected children/adolescents were initiated on ART. Overall, 487 (23.2%) deaths were registered (122 per month) and among them, 7 (15.9%) were HIV-positive; mainly due to tuberculosis and malnutrition. CONCLUSION: The consistent rate of unknown HIV status among children/adolescents attending health facilities, the high acceptability rates of HIV testing and linkage to ART, underscore the feasibility and utility of an active case finding model, using multiple entry-points at the health facility, in achieving the 90-90-90 targets for paediatric HIV/AIDS in RLS.