Browsing by Author "Moodley D"

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Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa.
(2013-Jun) Chi BH; Stringer JS; Moodley D; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges--and opportunities--of improving health services for HIV-infected mothers and their children across the region.
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; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi.; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA.; Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.; Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD.; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.; Maternal and Pediatric Infectious Disease Branch, Division of Extramural Research, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.; Department of Obstetrics and Gynaecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.; University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.; Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi.; Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa.; Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe.; Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India.; Department of Pediatrics and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA.; Department of Pediatrics, Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.; Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
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; From the Department of Pathology, Johns Hopkins University School of Medicine (M.G.F.), and the Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health (T.E.T.), Baltimore, and the Division of AIDS, National Institute of Allergy and Infectious Diseases (D.G., K.L.K., R. Browning, L.P.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (G.K.S.), National Institutes of Health, Bethesda - all in Maryland; the Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston (M.Q., T.F., D.E.S.); the Retrovirology Core Laboratory, University of North Carolina School of Medicine, Chapel Hill (S.A.F., A.J.L.), and FHI 360, Durham (A.S.C.) - both in North Carolina; the UCLA Center for Clinical AIDS Research and Education, Los Angeles (J.S.C.); St. Jude Children's Research Hospital, Memphis, TN (P.M.F.); the Department of Obstetrics and Gynecology, College of Health Sciences, University of Zimbabwe, Harare (T.C.); Anova Health Institute (J.M.), Perinatal HIV Research Unit, University of the Witwatersrand, Faculty of Health Sciences (A.V.), and Empilweni Services and Research Unit (R.S.), Johannesburg, School of Public Health and Family Medicine, University of Cape Town (J.M.), and the Department of Obstetrics and Gynaecology, Stellenbosch University (G.B.T.), Cape Town, and the Centre for the AIDS Programme of Research in South Africa-Umlazi Clinical Research Site (D.M.) and Durban Paediatric HIV (R. Bobat), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban - all in South Africa; the University of North Carolina Project, Kamuzu Central Hospital-Tidziwe Center, Lilongwe, Malawi (F.E.M.); Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda (M.O.); the Department of Obstetrics and Gynecology, B.J. Medical College, Pune, India (R. Bhosale); the Centre for Infectious Disease Research in Zambia, Lusaka, Zambia (B.H.C.); Kilimanjaro Christian Medical Center-Duke University Collaboration, Moshi, Tanzania (P.M.); Frontier Science and Technology Research Foundation, Amherst, NY (M.B.); and the Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC (L.M.M.).; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Soweto.; Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; National Institute of Allergy and Infectious Diseases/NIH, Rockville, MD.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Global Women's Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; St. Jude Children's Research Hospital, Memphis, TN.; B.J. Government Medical College, Department of Paediatrics, Pune, India.; Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA.; MU-JHU Research Collaboration; Upper Mulago Hill Road, Kampala, Uganda.; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA.; Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg.; University of North Carolina Project Malawi, Tidziwe Centre, Lilongwe, Malawi.; Centre for Infectious Disease Research in Zambia, George CRS, Lusaka, Zambia.; Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, University of KwaZulu Natal, Congella, South Africa.; Kamuzu University of Health Sciences-Johns Hopkins Research Project, Blantyre, Malawi.; Child, Adolescent and Women's Health Department, Faculty of Medicine and Health Sciences, University of Zimbabwe, Avondale.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.; Kilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute and Kilimanjaro Christian Medical University College/Kilimanjaro CRS, Moshi, Tanzania.; University of Zimbabwe Clinical Trials Research Centre, Belgravia, Harare, Zimbabwe.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
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; Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.; Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.; Department of Pediatrics, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN.; Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.; Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.; Elisabeth Glaser Pediatric AIDS Foundation, Washington, DC.; Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi.; Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa.; University of Zimbabwe-University of California, San Francisco, Harare, Zimbabwe.; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA.; Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India.; Department of Obstetrics and Gynecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.; University of North Carolina-Lilongwe, Lilongwe, Malawi.; Department of Paediatrics and Child Health, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.; Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; George Clinic, Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.