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Tonse Pamodzi: Developing a combination strategy to support adherence to antiretroviral therapy and HIV pre-exposure prophylaxis during pregnancy and breastfeeding.
Hill, LM, Saidi, F, Freeborn, K, Amico, KR, Rosenberg, NE, Maman, S, Phanga, T, Tsidya, M, Chirwa, S, Zimba, C, et al
PloS one. 2021;(6):e0253280
Abstract
To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi ("all of us together"), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT.
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Vitamin D-binding protein in cervicovaginal fluid as a non-invasive predictor of intra-amniotic infection and impending preterm delivery in women with preterm labor or preterm premature rupture of membranes.
Kook, SY, Park, KH, Jang, JA, Kim, YM, Park, H, Jeon, SJ
PloS one. 2018;(6):e0198842
Abstract
OBJECTIVE To determine whether vitamin D-binding protein (VDBP) in cervicovaginal fluid (CVF) is independently predictive of intra-amniotic infection and imminent spontaneous preterm delivery (SPTD, delivery within 48 hours) in women with preterm labor with intact membranes (PTL) or preterm premature rupture of membranes (PPROM). METHOD This was a single-center retrospective cohort study. CVF samples for VDBP assays were obtained along with serum C-reactive protein (CRP) levels immediately after amniocentesis in consecutive women with PTL (n = 148) or PPROM (n = 103) between 23.0 and 34.0 weeks of gestation. VDBP levels in CVF were determined by enzyme-linked immunosorbent assay kits. The primary outcome measures were intra-amniotic infection [defined as positive amniotic fluid (AF) culture] and SPTD within 48 hours after sampling. RESULTS In the multivariable analysis, elevated VDBP levels in CVF samples of PTL women were significantly associated with intra-amniotic infection and imminent preterm delivery, even after adjusting for potential confounders (e.g., gestational age at sampling, parity, and serum CRP). However, these relationships were not found in women with PPROM. In women with PTL, the areas under receiver operating characteristic curves of CVF VDBP level for predicting intra-amniotic infection and imminent preterm delivery were 0.66 and 0.71, with cut-off values of 1.76 μg/mL (sensitivity of 64.3% and specificity of 78.4%) and 1.37 μg/mL (sensitivity of 65.4% and specificity of 72.6%), respectively. The CVF VDBP levels were significantly higher in women with PPROM than in those with PTL. CONCLUSIONS VDBP in the CVF independently predicts intra-amniotic infection and imminent preterm delivery in women with PTL, whereas in women with PPROM, an elevated VDBP level in CVF is not associated with increased risks of these two outcome variables.
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Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women.
Brites, C, Nóbrega, I, Luz, E, Travassos, AG, Lorenzo, C, Netto, EM
HIV clinical trials. 2018;(3):94-100
Abstract
Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA <50 copies per mL), in all patients who received at least one dose of study drugs (modified intention-to-treat analysis). Missing information was treated as failure. We assessed safety in all patients. Results We enrolled and randomly assigned treatment to 33 patients (17 in raltegravir group) between June 2015 and June 2017. The study was interrupted by the IRB because a significant difference between arms was detected in an interim analysis. All patients completed follow up at delivery. At delivery, virological suppression was achieved by 13/17 (76.5%) of patients in raltegravir group, versus 4/16 (25.0%) in lopinavir/ritonavir group (RR 3.1, 95% CI: 1.3-7.4). Patients in raltegravir group had significantly higher proportion of virological suppression at 2, 4, and 6 weeks than lopinavir/ritonavir group. Adverse events were most of mild intensity, but patients in lopinavir/ritonavir group had significantly more gastrointestinal adverse events. There was neither discontinuation nor deaths in this trial. Conclusion Raltegravir might be a first-line option for treatment of HIV-infected late-presenting pregnant women.
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Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial.
Steinhoff, MC, Katz, J, Englund, JA, Khatry, SK, Shrestha, L, Kuypers, J, Stewart, L, Mullany, LC, Chu, HY, LeClerq, SC, et al
The Lancet. Infectious diseases. 2017;(9):981-989
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Abstract
BACKGROUND Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. METHODS In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17-25 weeks vs 26-34 weeks). Women were eligible if they were married, 15-40 years of age, 17-34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0-180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov, number NCT01034254. FINDINGS From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (-16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0-6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (-19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3-25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0-6 months was similar in each group (50 in the placebo group and 61 in the vaccine group). No serious adverse events were associated with receipt of immunisation. INTERPRETATION Year-round maternal influenza immunisation significantly reduced maternal influenza-like illness, influenza in infants, and low birthweight over the entire course of the study, indicating the strategy could be useful in subtropical regions. FUNDING Bill & Melinda Gates Foundation.
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Exclusive breastfeeding among women taking HAART for PMTCT of HIV-1 in the Kisumu Breastfeeding Study.
Okanda, JO, Borkowf, CB, Girde, S, Thomas, TK, Lecher, SL
BMC pediatrics. 2014;:280
Abstract
BACKGROUND One of the most effective ways to promote the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings is to encourage HIV-positive mothers to practice exclusive breastfeeding (EBF) for the first 6 months post-partum while they receive antiretroviral therapy (ARV). Although EBF reduces mortality in this context, its practice has been low. We studied the rate of adherence to EBF and assessed associated maternal and infant characteristics using data from a phase II PMTCT clinical trial conducted in Western Kenya which included a counseling intervention to encourage EBF by all participants. METHODS We analyzed data from the Kisumu Breastfeeding Study (KiBS), conducted between July 2003 and February 2009. This study enrolled a total of 522 HIV-1 infected pregnant women. Data on breastfeeding were available for 480 mother-infant pairs. Infant feeding and general nutrition counseling began at 35 weeks gestation and continued throughout the 6 month post-partum intervention period, following World Health Organization (WHO) infant feeding guidelines. Data on infant feeding were collected during routine clinic visits and home visits using food frequency questionnaires and dietary recall methods. Participants were instructed to exclusively breastfeed until initiation of weaning at 5.5 months post-partum. We used Kaplan-Meier methods to estimate the rates of EBF at 5.25 months post-partum, stratified by maternal and infant characteristics measured at enrollment, delivery, and 2 weeks post-partum. RESULTS The estimated EBF rate at 5.25 months post-partum was 80.4%. Only 3% of women introduced other foods (most commonly water with or without glucose, cow's milk, formula, and fruit) by 2 months; this percentage increased to 5% of women by 4 months. Women who had ≥3 previous births (p < 0.01) and who were not living with the infant's father (p = 0.04) were more likely to exclusively breastfeed. Mixed feeding was more common for male infants than for female infants (p = 0.04). CONCLUSION Exclusive breastfeeding was common in this clinical trial, which emphasized EBF as a best practice until infants reached 5.5 months of age. Counseling initiated prior to delivery and continued during the post-partum period provided a consistent message reinforcing the benefits of EBF. The findings from this study suggest high adherence to EBF in resource limited settings can be achieved by a comprehensive counseling intervention that encourages EBF.
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Safety of lamivudine treatment for chronic hepatitis B in early pregnancy.
Yi, W, Liu, M, Cai, HD
World journal of gastroenterology. 2012;(45):6645-50
Abstract
AIM: To evaluate the safety of lamivudine (LAM) treatment for chronic hepatitis B in early pregnancy. METHODS A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study. All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus, human immunodeficiency virus, cytomegalovirus, or other viruses. All infants received passive-active immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines (0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B. Adverse events were observed throughout the entire pregnancy and perinatal period, and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus (HBV) was evaluated. All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV mother-to-infant transmission blocking rate were compared with the literature. RESULTS Among the 92 pregnant women, spontaneous abortions occurred in 11 cases, while 3 mothers had a second pregnancy after the initial abortion; 72 mothers delivered 73 live infants, of whom 68 infants were followed up for no less than 6 mo, and 12 mothers were still pregnant. During pregnancy, the main maternal adverse events were vaginitis (12/72, 16.7%), spontaneous abortion (11/95, 11.6%), and gestational diabetes (6/72, 8.3%); only one case had 1-2 degree elevation of the creatine kinase level (195 U/L). During the perinatal period, the main maternal adverse events were premature rupture of the membranes (8/72, 11.1%), preterm delivery (5/72, 6.9%), and meconium staining of the amniotic fluid (4/72, 5.6%). In addition, 2 infants were found to have congenital abnormalities; 1 had a scalp hemangioma that did not change in size until 7 mo, and the other had early cerebral palsy, but with rehabilitation training, the infant's motor functions became totally normal at 2 years of age. The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment. In only 2 cases, mother-to-infant transmission blocking failed; the blocking rate was 97.1% (66/68), which was higher than has been previously reported. CONCLUSION Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.
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In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection.
Marinda, ET, Moulton, LH, Humphrey, JH, Hargrove, JW, Ntozini, R, Mutasa, K, Levin, J
International journal of epidemiology. 2011;(4):945-54
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Abstract
OBJECTIVE The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted. METHODS The risk of MTCT in utero and intra-partum was assessed comparing different groups defined by BED and CD4 cell count, adjusting for background factors using multinomial logistic models. RESULTS Compared with women with BED ≥ 0.8/CD4 ≥ 350 (typical of HIV-1 chronic patients) there was insufficient evidence to conclude that women presenting with BED < 0.8/CD4 ≥ 350 (typical of recent infections) were more likely to transmit in utero [adjusted odds ratio (aOR) = 1.37, 96% confidence interval (CI) 0.90-2.08, P = 0.14], whereas women with BED < 0.8/CD4 200-349 (possibly recently infected patients) had a 2.57 (95% CI 1.39-4.77, P-value < 0.01) odds of transmitting in utero. Women who had BED < 0.8/CD4 < 200 were most likely to transmit in utero (aOR 3.73, 95% CI 1.27-10.96, P = 0.02). BED and CD4 cell count were not predictive of intra-partum infections. CONCLUSIONS These data provide evidence that in utero transmission of HIV might be higher among women who seroconvert during pregnancy.
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Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study.
Kilewo, C, Karlsson, K, Massawe, A, Lyamuya, E, Swai, A, Mhalu, F, Biberfeld, G, ,
Journal of acquired immune deficiency syndromes (1999). 2008;(3):315-23
Abstract
OBJECTIVE To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period. DESIGN An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra). METHODS HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration. RESULTS There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL. CONCLUSIONS The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.
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Effect of vitamin supplementation to HIV-infected pregnant women on the micronutrient status of their infants.
Baylin, A, Villamor, E, Rifai, N, Msamanga, G, Fawzi, WW
European journal of clinical nutrition. 2005;(8):960-8
Abstract
OBJECTIVE We examined whether supplementation with vitamin A and/or vitamins B, C, and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A, B12, and E in their infants during the first 6 months of life. DESIGN We carried out a randomized clinical trial among 716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated to receive a daily oral dose of one of four regimens: vitamin A, multivitamins (B, C, and E), multivitamins including A, or placebo. Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period. The serum concentration of vitamins A, E and B12 was measured in infants at 6 weeks and 6 months postpartum. RESULTS Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks (mean difference=0.09 micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6 months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001, respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1 micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency. CONCLUSIONS Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age.
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Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension.
Merchant, AT, Msamanga, G, Villamor, E, Saathoff, E, O'brien, M, Hertzmark, E, Hunter, DJ, Fawzi, WW
The Journal of nutrition. 2005;(7):1776-81
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Abstract
Hypertension during pregnancy increases fetal growth retardation, preterm deliveries, and perinatal deaths, and yet its causes remain unclear. In HIV-infected women, preterm birth additionally increases the risk of HIV transmission to the infant. Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy. Vitamin intake can reduce oxidative stress and improve endothelial function. We therefore evaluated the effect of multivitamin (20 mg thiamine, 20 mg riboflavin, 25 mg B-6, 50 microg B-12, 500 mg C, 30 mg E, and 0.8 mg folic acid) and vitamin A supplements (30 mg beta-carotene plus 5000 IU preformed vitamin A) in relation to hypertension during pregnancy (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy). In a double-blind, placebo-controlled, randomized, clinical trial, conducted among 1078 HIV-positive pregnant Tanzanian women, those who received multivitamins were 38% less likely to develop hypertension during pregnancy than those who did not [relative risk (RR) = 0.62, 95% CI 0.40-0.94, P = 0.03]. There was no overall effect of vitamin A on hypertension during pregnancy (RR = 1.00, 95% CI 0.66-1.51, P = 0.98). Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure (>120 vs. < or = 120 mm Hg) (RR = 6.02, 95%CI 2.59-13.97, P < 0.001), and those with higher mid-upper arm circumference (RR = 1.12, 95% CI 1.04-1.19, P = 0.002). Taking multivitamins containing vitamins B, C, and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby.