Maternal Viral Load Research Articles

Prevention of vertical transmission of HIV in Khayelitsha, South Africa: A contemporary review of services after 20 years.

The first vertical transmission of HIV prevention (VTP) programme in South Africa was launched in 1999 in Khayelitsha, Western Cape Province (WC). Since then, VTP guidelines have expanded in complexity and scope. To describe contemporary VTP uptake in Khayelitsha and quantify vertical transmission (VT) risk factors based on linked routine electronic health data. In the WC, all patients at public health facilities have a unique identifier allowing linkage across electronic health platforms through a health information exchange hosted within the WC Department of Health. We conducted a cohort analysis of mother-infant pairs where the mother was living with HIV and attended any obstetric care in Khayelitsha in 2017. Descriptive statistics assessed VTP coverage along the care cascade, including maternal viral load (VL) testing and early infant diagnosis (EID). Logistic regression analysis quantified a priori-defined risk factors associated with VT. Antenatal HIV prevalence in the cohort was 31.3%, and VT was 1.8% by 12 months. Of women living with HIV, 88.3% knew of their positive status at the first antenatal visit and 77.9% were already receiving antiretroviral therapy (ART). Most women diagnosed prior to delivery (94.5%) were initiated on ART; 85.0% received an antenatal VL test, of whom 88.0% were virologically suppressed. Women who were not virally suppressed had a five-fold (adjusted odds ratio (aOR) 5.3; 95% confidence interval (CI) 2.5 - 12.3) increased VT risk compared with those who were suppressed. Women who attended no antenatal care were at higher risk of VT (aOR 1.6; 95% CI 0.7 - 3.6) than those who did attend. EID coverage was suboptimal: a birth HIV polymerase chain reaction (PCR) test was available for 79.2% of infants, and a low proportion with a negative birth test had a repeat test around 10 weeks (57.9%). Data linkage identified an additional 15 infants living with HIV who were not detected by HIV-PCR testing alone. Although most women presented to care already knowing their HIV status, ART initiation was suboptimal prior to the first antenatal visit but improved over the course of pregnancy. The VT rate based on laboratory HIV-PCR testing alone underestimated HIV transmission: linked data from multiple sources suggested higher VT than programme-reported rates based on HIV-PCR testing alone.

Change in HIV-related characteristics of children hospitalised with infectious diseases in Western Cape, South Africa, 2008-2021: a time trend analysis.

With the scaling up of vertical HIV transmission prevention programmes, the HIV-related population profile of children in South Africa has shifted. We described temporal changes in HIV-related characteristics of children, aged ≤3 years (up to the third birthday), with infectious disease hospitalisations across the Western Cape province. We used routinely collected electronic data to identify children born in the Western Cape with infectious disease hospital records for lower respiratory tract infections, diarrhoea, meningitis and tuberculous meningitis, from 2008 to 2021. Linked maternal and child unique identifiers were used to extract pregnancy, HIV-related, laboratory, pharmacy and hospitalisation data. We described temporal changes in child HIV exposure and acquisition status, timing of maternal HIV diagnosis and antiretroviral therapy (ART) start, infant exposure to maternal ART and timing thereof, and maternal CD4 and HIV viral load closest to delivery. We used logistic and multinomial regression to assess changes in characteristics between the Pre-Option B+ (2008-2013), Option B+ (2013-2016) and Universal ART periods (2016-2021). Among 52,811 children aged ≤3 years with hospitalisations, the proportion living with HIV dreased from 7.0% (2008) to 1.1% (2021), while those exposed to HIV and uninfected increased from 14.0% (2008) to 16.1% (2021) with a peak of 18.3% in 2017. Among mothers with HIV (n = 9873), the proportion diagnosed with HIV and starting ART before pregnancy increased from 20.2% to 69.2% and 5.8% to 59.0%, respectively, between 2008 and 2021. Children hospitalised during the Universal ART period had eight times higher odds (Odds Ratio: 8.41; 95% CI: 7.36-9.61) of exposure to maternal ART versus children admitted Pre-Option B+. Among mothers of children exposed to HIV and uninfected with CD4 records (n = 7523), the proportion with CD4 <350 cells/μl decreased from 90.6% (2008) to 27.8% (2021). In recent years, among children hospitalised with infectious diseases, there were fewer children with perinatally acquired HIV, while an increased proportion of those without HIV acquisition are exposed to maternal HIV and ART. There is a need to look beyond paediatric HIV prevalence and consider child exposure to HIV and ART among children without HIV, when assessing the HIV epidemic's impact on child health services.

HIV Drug Resistance Mutations and Subtype Profiles among Pregnant Women of Ho Chi Minh City, South Vietnam.

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15-49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71-85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31-72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72-18.10%), and to NNRTIs in 44.26% (95% CI: 31.55-57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection.

Development and Implementation of an Interdisciplinary Model for the Management of Breastfeeding in Women With HIV in the United States: Experience From the Children's Hospital Colorado Immunodeficiency Program.

Women with HIV in high-income settings have increasingly expressed a desire to breastfeed their infants. Although national guidelines now acknowledge this choice, detailed recommendations are not available. We describe the approach to managing care for breastfeeding women with HIV at a single large-volume site in the United States. We convened an interdisciplinary group of providers to establish a protocol intended to minimize the risk of vertical transmission during breastfeeding. Programmatic experience and challenges are described. A retrospective chart review was conducted to report the characteristics of women who desired to or who did breastfeed between 2015 and 2022 and their infants. Our approach stresses the importance of early conversations about infant feeding, documentation of feeding decisions and management plans, and communication among the health care team. Mothers are encouraged to maintain excellent adherence to antiretroviral treatment, maintain an undetectable viral load, and breastfeed exclusively. Infants receive continuous single-drug antiretroviral prophylaxis until 4 weeks after cessation of breastfeeding. From 2015 to 2022, we counseled 21 women interested in breastfeeding, of whom 10 women breastfed 13 infants for a median of 62 days (range, 1-309). Challenges included mastitis (N = 3), need for supplementation (N = 4), maternal plasma viral load elevation of 50-70 copies/mL (N = 2), and difficulty weaning (N = 3). Six infants experienced at least 1 adverse event, most of which were attributed to antiretroviral prophylaxis. Many knowledge gaps remain in the management of breastfeeding among women with HIV in high-income settings, including approaches to infant prophylaxis. An interdisciplinary approach to minimizing risk is needed.

Nasopharyngeal SARS-CoV-2 load and perinatal outcomes after maternal infection diagnosed close to delivery.

The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients. To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy. International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19. The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p=0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p=0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p=0.336), 5' Apgar scores (adjusted B: -0. -9.8e-4 (95%CI: -0.01; 0.01); p=0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p=0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p=0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity. The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes.

SARS-CoV-2 Viral Load in Pregnant Women and Association with Maternal Disease Severity and Neonatal Outcomes

Background: The outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created unexpected impacts worldwide. Objectives: This study aimed to examine the association of SARS-CoV-2 viral load in pregnant women with maternal disease severity and neonatal outcomes. Methods: In this retrospective cohort study, 55 pregnant women infected with SARS-CoV-2 and their newborn infants were included. The association between maternal viral load (tested by cycle threshold) and maternal disease severity/neonatal outcomes was examined. Results: Infants had a median gestational age of 38 (29 - 41) weeks and birth weight of 3200 (630 - 4570) grams. The median Ct value of pregnant women was 30 (20 - 37). No significant difference was detected among mild, moderate or severely ill pregnant women in terms of median Ct values (30, 28.5, and 30, respectively; P &gt; 0.05). The median Ct value of pregnant women who gave preterm delivery was similar to those who had term delivery [30 (21 - 36) vs. 30 (25 - 35); P &gt; 0.05]. The median Ct values were similar among pregnant women who died or survived [32.5 (30 - 34) vs. 30 (21 - 36); P &gt; 0.05]. Preterm delivery rates and overall mortality were not associated with SARS-CoV-2 RT-qPCR Ct values, (r = 0.04, P &gt; 0.05). No correlation was found between maternal SARS-CoV-2 viral load and maternal disease severity/neonatal outcomes. Conclusions: To the best of our knowledge, this study was the first one examining the association between maternal SARS-CoV-2 viral load and maternal/neonatal outcomes. It was suggested that viral load may not have been used for predicting the severity of maternal disease and maternal/neonatal outcomes.

Antiretroviral Options and Treatment Decisions During Pregnancy.

The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide.

Antiretroviral postnatal prophylaxis to prevent HIV vertical transmission: present and future strategies.

Maternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, with half of these infections occurring during breastfeeding. A consultative meeting of stakeholders was held to review the current state of PNP globally, including the implementation of WHO PNP guidelines in different settings and identifying the key factors affecting PNP uptake and impact, with an aim to optimize future innovative strategies. WHO PNP guidelines have been widely implemented with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk-stratification and provide an enhanced PNP regimen for all infants exposed to HIV, while other programmes provide infant daily nevirapine antiretroviral (ARV) prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk stratification approach may be more relevant for high-performing vertical transmission prevention programmes, while a simplified non-risk stratified approach may be more appropriate for sub-optimally performing programmes given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants who are found to be exposed to HIV should be considered at high risk for HIV acquisition. All settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. There are several challenges in enhanced and extended PNP implementation, including ARV stockouts, lack of appropriate formulations, lack of guidance on alternative ARV options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and in inadequate retention throughout the duration of breastfeeding. Tailoring PNP strategies to a programmatic context may improve access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV options and technologies that enable simplification of regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be prioritized to optimize the effect of PNP in the prevention of vertical HIV transmission.

Prevention of mother-to-child transmission of HIV in Kermanshah, west of Iran from 2014 to 2021

BackgroundThis study aimed to evaluate the implementation of the prevention of mother-to-child transmission (PMTCT) of the HIV-PMTCT program in Kermanshah, west of Iran, from 2014 to 2021.MethodsThe data of all HIV-infected mothers and their infants who were monitored by the Kermanshah behavioral diseases counseling center was extracted and recorded in a checklist.ResultsOut of 95 included infant, 45 (47.4%) were girls and 50 (52.6%) were boys. The mothers were mostly infected with HIV via their infected spouse. The pregnancies of 77 cases (82.1%) were in accordance with the national guideline. The average length of treatment for this group was 185 days. Of the 18 mothers who did not receive treatment, nine were diagnosed during childbirth and nine had no available information. All infants born from infected mothers underwent after-birth-antiretroviral prophylaxis, and all remained healthy. There was no statistically significant relationship between the birth weight and height of neonates with maternal age, maternal last viral load, disease stage, education, and maternal CD4 levels. Only a statistically significant relationship was observed between the duration of treatment and the infants’ weight.ConclusionThe results suggest the feasibility and effectiveness of the PMTCT program for HIV-positive mothers in Kermanshah. It seems that if pregnant HIV-positive women are diagnosed early and covered by a good prevention program on time, the risk of HIV to their babies will be reduced, significantly.

1344. Infectious Morbidity and Mortality of HIV-Exposed, Uninfected Infants Compared with HIV-Unexposed Uninfected Infants in Botswana

Abstract Background Studies have shown increased risk for infection-related hospitalizations among infants HIV-exposed-uninfected (HEU) compared to infants HIV-unexposed-uninfected (HUU). However, limited data exist during an era of expanded antiretroviral therapy (ART) and improved healthcare access in pregnancy. Methods The Tshilo Dikotla study prospectively enrolled pregnant women ≥ 18 years old, both living with HIV (WLHIV) and HIV-seronegative, in Botswana, following mother-infant pairs through 3 years postpartum. Pregnant WLHIV received tenofovir/lamivudine or emtricitabine plus efavirenz or dolutegravir. For this analysis, the primary outcome, infectious morbidity, was hospitalization or death due to an infectious cause for infants in the first 12 months of life. Log-binomial models were fit to assess the association between in utero HIV exposure status and infectious morbidity. Subgroup analysis among infants HEU was performed to assess associations between timing of maternal ART initiation (pre-conception vs. during pregnancy) and infant infectious morbidity. Results Of 464 infants, 314 (67.7%) were HEU. Maternal age was higher among WLHIV (30.3 vs. 24.6 years; p &amp;lt; 0.01), as was gravidity (3.0 vs.1.0; p &amp;lt; 0.01). The proportion of WLHIV reporting senior secondary or tertiary education was lower (43.3% vs 72.0%; p&amp;lt; 0.01). A total of 35 (7.5%) infants were hospitalized/died due to infectious causes [26 (8.3%) HEU vs. 9 (6.0%) HUU (p=0.38)]. The most frequent infections were pneumonia and diarrhea/gastroenteritis. There was no significant difference in infectious morbidity by infant HIV exposure status [adjusted Odds Ratio (aOR), 1.17; 95% Confidence Interval (CI), 0.49, 2.81] after adjusting for maternal age, gravidity, income, and education. No association was found between timing of maternal ART initiation and infectious morbidity (aOR 0.60; 95% CI, 0.25, 1.40) among infants who were HEU, after additionally adjusting for maternal CD4 count and HIV viral load. Characteristics of infants by in utero HIV exposure status Conclusion In this small sub-Saharan African cohort, no detectable associations were observed by infant HIV exposure status or timing of maternal ART initiation and infant infectious morbidity. Larger studies are needed to confirm these findings. Disclosures All Authors: No reported disclosures.

Brief Report: HIV-Positive and Breastfeeding in High-Income Settings: 5-Year Experience From a Perinatal Center in Germany.

Exclusive breastfeeding is recommended for women living with HIV (WLWH) in low-income-but not in high-income-countries, where milk substitutes are preferred. Some guidelines for high-income countries opted for a shared decision-making process regarding breastfeeding in optimal scenarios with adherence to antiretroviral therapy (cART), suppressed maternal viral load (mVL), and clinical monitoring. Although vertical transmission (VT) risk under cART is estimated below 1% in low-income settings, data from high-income countries are rare. We retrospectively analyzed all 181 live births from WLWH at the LMU Munich university hospital perinatal center in Germany between January 2016 and December 2020. We focused on VT, suppressed mVL and optimal scenario rates, breastfeeding frequency, cART regimens, and infant prophylaxis. All women were counseled according to current guidelines, foremost recommending avoidance of breastfeeding. In the 5-year cohort, no VT was observed. One hundred fifty-one WLWH (83.4%) decided not to breastfeed, even in optimal scenarios. Thrity infants (16.6%) were nursed, of which 25 were within an optimal scenario, whereas in 5 cases, breastfeeding was performed with a detectable VL in pregnancy or the postpartum period. All WLWH were treated with cART at delivery, and 91.7% sustained suppressed mVL. Zidovudine infant prophylaxis was given between 2 and 8 weeks but not necessarily over the whole breastfeeding duration and was declined from 5 breastfeeding WLWH. Although the cohort is too small to assess VT risk through breastfeeding with cART-suppressed mVL, breastfeeding might be an alternative even in high-income countries, but further studies are needed.

Evaluation of plasma viral-load monitoring and the prevention of mother-to-child transmission of HIV-1 in three health facilities of the Littoral region of Cameroon

Prevention of mother-to-child transmission (PMTCT) has reduced HIV incidence among new-borns. However, PMTCT remains concerning in sub-Saharan Africa due to bottlenecks including viral load (VL) monitoring during pregnancy. We assessed VL coverage and materno-foetal outcomes of pregnancy among HIV-infected women within the Cameroonian context. A hospital-based study was conducted among HIV-infected mothers and their babies in three facilities of the Littoral region of Cameroon from January 2019 to May 2021. Maternal VL-coverage was monitored during pregnancy (VL&gt;1000 copies/ml or unknown were classified as MTCT high-risk group); HIV early infant diagnosis (EID) was evaluated by PCR at six-weeks after birth, and EID results were analysed according to maternal VL; p&lt;0.05 was considered statistically significant. Of 135 HIV-infected pregnant women enrolled (median [IQR] age 39 [27-37] years), VL-coverage during antenatal care (ANC) was 50.4% (68/135), with a lower VL-coverage in 2019 (37.5% vs. 61.9%, p = 0.0069). Married women vs. single (61.8% vs. 42.5%, p = 0.0275) and those on treatment before vs. during pregnancy (56.7% vs. 5.8%, p = 0.0043) had a higher VL-coverage, respectively. Among those with known VL, 10.3% (7/68) had high (VL&gt;1000 copies/mL), 22.1% (15/68) had low (50-1000 copies/mL), and 67.6% (46/68) had undetectable (&lt;50 copies/mL) VL, suggesting an overall viral suppression (&lt;1000copies/mL) of 89.7% (61/68). Vaginal delivery was 80.75% (109/135) regardless of VL, including 81.1% (59/74) women in the high-risk group. EID coverage was 88.1% (119/135) and the rate of HIV-1 MTCT was 1.68% (2/119). Both HIV-positive infants were from the high-risk group, had prolonged labour, had vaginal delivery and were breastfed. In these Cameroonian settings, VL-coverage remains suboptimal (below 90%) among ANC attendees, and women at high-risk of MTCT mainly have vaginal delivery. Viral suppression rate remains below the target (below 90%) for accelerating the elimination of MTCT. HIV-MTCT persists, and might be driven essentially by poor VL monitoring. Thus, achieving an optimal PMTCT performance requires a thorough compliance to virologic assessment during ANC.

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa.

Despite South Africa’s substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks’ gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants.

Effectiveness of prophylaxis for hepatitis B in infants born to mothers serologically positive in Benghazi Medical center

Background: The seroprevalence of HBs Ag among the general population in Libya was found to be 2.2 %. Libya is therefore considered an area of intermediate endemicity for hepatitis B. vertical transmission is considered as the main route of spread of this infection. Trans placental (intra-uterine) transmission is presumed to cause the minority. Risk factors for transmission of HBV include maternal HBe Ag positivity, HBs Ag titer, and HBV viral load. Active immunization with hepatitis B vaccine (Hep. B vaccine), and hepatitis B immunoglobulin (HBIG) is 85-95% effective in preventing the disease. The objective of the study: To assess the effectiveness of hepatitis B vaccine and hepatitis B immunoglobulin in the prevention of the Hep. B. virus transmission and to study the factors that affected the immune response of the newborn babies of mothers with hepatitis B positive infection during pregnancy. Patients &amp; Methods: A longitudinal cross-section study included 40 babies born to mothers with hepatitis B during the period from 1.1.2017 To 1.3.2019 at Benghazi Medical Center. The newborn babies have been immunized with Hepatitis BIG and Hepatitis B vaccine at birth, and further 3 doses of hep. B vaccine and HBIG. Multivariable analyses were done to assess the statistical significance associated with responders and nonresponders to HB immune prophylaxis. Results: all babies were negative for hepatitis Bs Ag in 40(100%), 35 (88%) their viral load was 10 mlIU/ml) in More than two-thirds (60%) and (63%) of infants at 9 months and 12 months respectively. Birth weight &gt;2.5 kg was significantly associated with immune response &gt;10 mIU/ml, whereas, Maternal viral load, time of administration of HBIG, and hep. B vaccine, gestational age, mode of delivery, type of feeding were statistically not significant. Conclusion: the study reported that all the newborn babies were negative for hepatitis B sAg after delivery, more than two-thirds of the babies were responders to immune-prophylaxis, and birth weight of &gt;2.5kg was significantly related to high immune-response.

Breastfeeding and women living with HIV: Is it possible to move beyond the avoidance?

The risk of mother-to-infant transmission of HIV 1 during breastfeeding ranges from 10% to 15% in the absence of maternal Antiretroviral Therapy (ART) and infant Antiretroviral (ARV) prophylaxis. WHO guidelines 2016 recommend women living with HIV and fully supported for ART adherence should breastfeed for at least 12 months and up to 24 months or longer. Anyway, in high-income settings, women living with HIV are suggested to avoid breastfeeding, regardless of maternal viral load or antiretroviral therapy status. The advantages of breastfeeding in low and middle-income settings are well recognized. This brief narrative review aims to summarize existing evidence on mechanisms and risk factors for HIV transmission during breastfeeding and the possible prevention strategies in the context of ART adherence.

HIV stigma limits the effectiveness of PMTCT in Guinea: the ANRS 12344-DIAVINA study.

Nearly half of HIV-infected children worldwide are born in West and Central African countries where access to prevention of mother-to-child transmission of HIV (PMTCT) programmes is still limited. WHO recommends reinforced antiretroviral prophylaxis for infants at high risk of mother-to-child transmission of HIV (MTCT) but its implementation needs further investigation in the field. The prospective ANRS 12344-DIAVINA study evaluated the feasibility of a strategy combining early infant diagnosis (EID) and reinforced antiretroviral prophylaxis in high-risk infants as identified by interviews with mothers at Ignace Deen Hospital, Conakry, Guinea. 6493 women were admitted for delivery, 6141 (94.6%) accepted HIV testing and 114 (1.9%) were HIV positive. Among these, 51 high-risk women and their 56 infants were included. At birth, a blood sample was collected for infant EID and reinforced antiretroviral prophylaxis was initiated in 48/56 infants (86%, 95% CI 77%-95%). Iron supplementation was given to 35% of infants for non-severe anaemia. Retrospective measurement of maternal plasma viral load (pVL) at delivery revealed that 52% of women had pVL &lt; 400 copies/mL attributable to undisclosed HIV status and/or antiretroviral intake. Undisclosed HIV status was associated with self-stigmatization (85% versus 44%, P = 0.02). Based on the results of maternal pVL at delivery, 'real' high-risk infants were more frequently lost to follow-up (44% versus 8%, P &lt; 0.01) in comparison with low-risk infants, and this was associated with mothers' stigmatization (69% versus 31%, P &lt; 0.01). Reinforced antiretroviral prophylaxis and EID at birth are widely feasible. However, mothers' self-disclosure of HIV status and antiretroviral intake do not allow adequate evaluation of MTCT risk, which argues for maternal pVL measurement near delivery. Furthermore, actions against stigmatization are crucial to improve PMTCT.

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study

Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. Unitaid.

Mother-to-Child Transmission of HIV Within 24 Months After Delivery in Women Initiating Lifelong Antiretroviral Therapy Pre/Post-Conception or Postnatally; Effects of Adolescent Girl and Young Woman Status and Plasma Viremia Late in Pregnancy

IntroductionMother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) can occur in pregnancy/in utero (IU), during childbirth/intrapartum (IP), or postpartum (PP) through breastfeeding from an infected mother to her infant. Burden of PP-MTCT and associated risk factors remain poorly described, especially in adolescent girls and young women (AGYW) aged 15–24 years. Furthermore, despite concerns on high postnatal seroconversions, there is paucity of data on the burden of subsequent MTCT rates.MethodsPregnant women ≥20 weeks of gestation were enrolled into the University of Zimbabwe Birth Cohort from four primary health centers in Harare, Zimbabwe. Mother–infant dyads were followed up from delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72, and 96 after birth. Women who were uninfected at baseline were re-tested for HIV on subsequent visits. Plasma HIV RNA was quantified using reverse transcriptase polymerase chain reaction. Exposed babies were tested for HIV using qualitative/quantitative proviral DNA PCR on dried blood spots. Maternal–infant factors were tested in univariable/multivariable regression analyses for HIV-MTCT predictors.ResultsA total of 600 HIV-uninfected and 608 HIV-infected pregnant women on Tenofovir/Lamivudine/Efavirenz regimen were enrolled from 2016 to 2019. Postnatal HIV incidence was 0.42 cases/100 women-years [95% confidence interval (CI): 0.12–1.1]. Postnatal seroconverters were less likely to have children/pregnancies sharing same father and unaware of their spouses/intimate partner’s HIV status: p = 0.008 and p = 0.02, respectively, compared with non-seroconverters.Overall HIV-MTCT rate was (15/549): 2.7% (CI: 1.3–4.1%); (7/93) 7.5% observed in AGYW against 1.7%; in women aged &amp;gt;24, p = 0.008. PP-MTCT was the predominant 9/15 (60%) route, followed by IP-MTCT 4/15 (26.6%), whereas IU and postnatal MTCT rates each contributed 6.7% of all infant infections. Postnatal MTCT incidence was 12.8 (CI: 0.3–71.4) infant HIV infections/100 child-years of breastfeeding; a rate 14 times higher than PP-MTCT rate in babies born to women HIV-infected pre/post-conception whose babies were HIV DNA PCR–negative at six weeks.Antenatal HIV RNA &amp;gt;1,000 copies/ml was independently associated with MTCT; odds ratio [CI: 9.3 (2.6–43.1)]. Infected infants’ pre–HIV treatment HIV RNA levels correlated positively with maternal viral load; Spearman’s rank correlation. r = 0.6; p = 0.03.DiscussionMothers were 9.3 times more likely to transmit if HIV RNA was &amp;gt;1,000 copies/ml, disproportionately occurring in vulnerable AGYW. Breastfeeding-associated PP-MTCT remains high; therefore, it is imperative that HIV-infected women commence antiretroviral therapy early in pregnancy to suppress HIV RNA until weaning to decrease the risk of MTCT and possibly reduce the severity of disease in infected infants. HIV-uninfected lactating mothers should be continuously counseled on the risks of postnatal seroconversion.www.clinicaltrials.gov, trial registration number: NCT04087239.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence

BackgroundThe World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers’ ART adherence may be suboptimal. We evaluate the inclusion of the mothers’ self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers’ VL result is not available at delivery.MethodsWe used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers’ adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%.ResultsAt delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants.ConclusionsIn the absence of a VL result, mothers’ self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

Interpersonal therapy versus antidepressant medication for treatment of postpartum depression and anxiety among women with HIV in Zambia: a randomized feasibility trial.

IntroductionPostpartum depression (PPD) is a prevalent and debilitating disease that may affect medication adherence and thus maternal health and vertical transmission among women with HIV. We assessed the feasibility of a trial of interpersonal psychotherapy (IPT) versus antidepressant medication (ADM) to treat PPD and/or anxiety among postpartum women with HIV in Lusaka, Zambia.MethodsBetween 29 October 2019 and 8 September 2020, we pre‐screened women 6–8 weeks after delivery with the Edinburgh Postnatal Depression Scale (EPDS) and diagnosed PPD or anxiety with the Mini International Neuropsychiatric Interview. Consenting participants were randomized 1:1 to up to 11 sessions of IPT or daily self‐administered sertraline and followed for 24 weeks. We assessed EPDS score, Clinical Global Impression‐Severity of Illness (CGI‐S) and medication side effects at each visit and measured maternal HIV viral load at baseline and final study visit. Retention, visit adherence, change in EPDS, CGI‐S and log viral load were compared between groups with t‐tests and Wilcoxon signed rank tests; we report mean differences, relative risks and 95% confidence intervals. A participant satisfaction survey assessed trial acceptability.Results78/80 (98%) participants were retained at the final study visit. In the context of the COVID‐19 pandemic, visit adherence was greater among women allocated to ADM (9.9 visits, SD 2.2) versus IPT (8.9 visits, SD 2.4; p = 0.06). EPDS scores decreased from baseline to final visit overall, though mean change was greater in the IPT group (−13.8 points, SD 4.7) compared to the ADM group (−11.4 points, SD 5.5; p = 0.04). Both groups showed similar changes in mean log viral load from baseline to final study visit (mean difference −0.43, 95% CI −0.32, 1.18; p = 0.48). In the IPT group, viral load decreased significantly from baseline (0.9 log copies/ml, SD 1.7) to final visit (0.2 log copies/ml, SD 0.9; p = 0.01).ConclusionsThis pilot study demonstrates that a trial of two forms of PPD treatment is feasible and acceptable among women with HIV in Zambia. IPT and ADM both improved measures of depression severity; however, a full‐scale trial is required to determine whether treatment of PPD and anxiety improves maternal–infant HIV outcomes.