Browsing by Author "Taha TE"

Now showing 1 - 7 of 7

Association of Maternal Viral Load and CD4 Count With Perinatal HIV-1 Transmission Risk During Breastfeeding in the PROMISE Postpartum Component.
(2021-Oct-01) Flynn PM; Taha TE; Cababasay M; Butler K; Fowler MG; Mofenson LM; Owor M; Fiscus S; Stranix-Chibanda L; Coutsoudis A; Gnanashanmugam D; Chakhtoura N; McCarthy K; Frenkel L; Beck I; Mukuzunga C; Makanani B; Moodley D; Nematadzira T; Kusakara B; Patil S; Vhembo T; Bobat R; Mmbaga BT; Masenya M; Nyati M; Theron G; Mulenga H; Shapiro DE
BACKGROUND: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. METHODS: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. CONCLUSIONS: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection.
Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1-negative women.
(2014-Feb) Balkus JE; Richardson BA; Rabe LK; Taha TE; Mgodi N; Kasaro MP; Ramjee G; Hoffman IF; Abdool Karim SS
BACKGROUND: The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). METHODS: Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7-10; intermediate = 4-6; normal = 0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition. RESULTS: In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits, and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21-2.19; BV: aHR, 2.40; 95% CI, 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10-2.14; BV: aHR, 2.23; 95% CI, 1.75-2.84). CONCLUSIONS: Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.
Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.
(2016-Nov-03) Fowler MG; Qin M; Fiscus SA; Currier JS; Flynn PM; Chipato T; McIntyre J; Gnanashanmugam D; Siberry GK; Coletti AS; Taha TE; Klingman KL; Martinson FE; Owor M; Violari A; Moodley D; Theron GB; Bhosale R; Bobat R; Chi BH; Strehlau R; Mlay P; Loftis AJ; Browning R; Fenton T; Purdue L; Basar M; Shapiro DE; Mofenson LM
BACKGROUND: Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS: We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS: The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS: Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).
Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.
(2024-Jul-15) Dadabhai S; Chou VB; Pinilla M; Chinula L; Owor M; Violari A; Moodley D; Stranix-Chibanda L; Matubu TA; Chareka GT; Theron G; Kinikar AA; Mubiana-Mbewe M; Fairlie L; Bobat R; Mmbaga BT; Flynn PM; Taha TE; McCarthy KS; Browning R; Mofenson LM; Brummel SS; Fowler MG
BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.
Predictors of stillbirth in sub-saharan Africa.
(2007-Nov) Chi BH; Wang L; Read JS; Taha TE; Sinkala M; Brown ER; Valentine M; Martinson F; Goldenberg RL
OBJECTIVE: To describe the incidence and predictors of stillbirth in a predominantly human immunodeficiency virus (HIV)-infected African cohort. METHODS: Human Immunodeficiency Virus (HIV) Prevention Trials Network (HPTN) 024 was a randomized controlled trial of empiric antibiotics to reduce chorioamnionitis-related perinatal HIV transmission. A proportion of HIV-uninfected individuals were enrolled to reduce community-based stigma surrounding the trial. For this analysis, only women who gave birth to singleton infants were included. RESULTS: Of 2,659 women enrolled, 2,434 (92%) mother- child pairs met inclusion criteria. Of these, 2,099 (86%) infants were born to HIV-infected women, and 335 (14%) were born to HIV-uninfected women. The overall stillbirth rate was 32.9 per 1,000 deliveries (95% confidence interval [CI] 26.1-40.7). In univariable analyses, predictors for stillbirth included previous stillbirth (odds ratio [OR] 2.3, 95% CI 1.2-4.3), antenatal hemorrhage (OR 14.4, 95% CI 4.3-47.9), clinical chorioamnionitis (OR 20.9, 95% CI 5.1-86.2), and marked polymorphonuclear infiltration on placental histology (OR 2.9, 95% CI 1.7-5.2). When compared with pregnancies longer than 37 weeks, those at 34-37 weeks (OR 1.7, 95% CI 0.8-3.4) and those at less than 34 weeks (OR 22.8, 95% CI 13.6-38.2) appeared more likely to result in stillborn delivery. Human immunodeficiency virus infection was not associated with a greater risk for stillbirth in either univariable (OR 1.5, 95% CI 0.7-3.0) or multivariable (adjusted OR 1.11, 95% CI 0.38-3.26) analysis. Among HIV-infected women, however, decreasing CD4 cell count was inversely related to stillbirth risk (P=.009). CONCLUSION: In this large cohort, HIV infection was not associated with increased stillbirth risk. Further work is needed to elucidate the relationship between chorioamnionitis and stillbirth in African populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00021671 LEVEL OF EVIDENCE: II.
Prevention of HIV-1 Transmission Through Breastfeeding: Efficacy and Safety of Maternal Antiretroviral Therapy Versus Infant Nevirapine Prophylaxis for Duration of Breastfeeding in HIV-1-Infected Women With High CD4 Cell Count (IMPAACT PROMISE): A Randomized, Open-Label, Clinical Trial.
(2018-Apr-01) Flynn PM; Taha TE; Cababasay M; Fowler MG; Mofenson LM; Owor M; Fiscus S; Stranix-Chibanda L; Coutsoudis A; Gnanashanmugam D; Chakhtoura N; McCarthy K; Mukuzunga C; Makanani B; Moodley D; Nematadzira T; Kusakara B; Patil S; Vhembo T; Bobat R; Mmbaga BT; Masenya M; Nyati M; Theron G; Mulenga H; Butler K; Shapiro DE
BACKGROUND: No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child transmission throughout the breastfeeding period. SETTING: Fourteen sites in Sub-Saharan Africa and India. METHODS: A randomized, open-label strategy trial was conducted in HIV-1-infected women with CD4 counts ≥350 cells/mm (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1-uninfected newborns. Randomization at 6-14 days postpartum was to mART or infant nevirapine (iNVP) prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother-infant pairs except those with infant HIV-1 infection at entry. RESULTS: Between June 2011 and October 2014, 2431 mother-infant pairs were enrolled; 97% of women were World Health Organization Clinical Stage I, median screening CD4 count 686 cells/mm. Median infant gestational age/birth weight was 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and 7 of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio 1.0, 96% repeated confidence interval 0.3-3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening, or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively). CONCLUSIONS: Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1-free survival at 24 months.
Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024.
(2005-Nov-04) Chi BH; Wang L; Read JS; Sheriff M; Fiscus S; Brown ER; Taha TE; Valentine M; Goldenberg R
OBJECTIVE: Despite a growing emphasis worldwide on complex and potent antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV-1 (MTCT), two-dose nevirapine (NVP) prophylaxis remains an important choice in many settings. We analyzed data from a multicenter clinical trial to determine whether timing of maternal or infant NVP was associated with MTCT between delivery and 6 weeks of age (intrapartum/early postnatal transmission; I/EP). METHODS: HIVNET 024 was a placebo-controlled, double-blind trial of empiric antibiotics to reduce chorioamnionitis-associated MTCT. This secondary analysis used data collected in the original randomized trial. Enrolled women were instructed to self-administer NVP at labor onset; infants were to receive a dose within 72 h of birth. RESULTS: Data regarding 1491 mother-infant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1% at 6 weeks. Almost all women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the combined pattern of both was taken into account through multivariate analysis. In the subset of women ingesting NVP or= 4 h). CONCLUSION: Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not appear to affect the risk of MTCT.