111 results on '"Bobat R"'
Search Results
2. Expression of HLA-G1 at the placental interface of HIV-1 infected pregnant women and vertical transmission of HIV
- Author
-
Moodley, S. and Bobat, R.
- Published
- 2011
- Full Text
- View/download PDF
3. The impact of human immunodeficency virus 1 on largyngeal airway obstruction in children
- Author
-
Jeena, P M, Bobat, R, Kindra, G, Pillay, P, Ramji, S, and Coovadia, H M
- Published
- 2002
4. Lymphocyte subset changes between 3 and 15 months of age in infants born to HIV-seropositive women in South Africa
- Author
-
Moodley, D., Bobat, R. A., Coovadia, H. M., Doorasamy, T., Munsamy, S., and Gouws, E.
- Published
- 1997
5. Caesarean section and vertical transmission of HIV-1
- Author
-
Moodley, D, Bobat, R A, Coutsoudis, A, and Coovadia, H M.
- Published
- 1994
6. Tuberculosis in HIV-infected South African children with complicated severe acute malnutrition
- Author
-
Adler, H., primary, Archary, M., additional, Mahabeer, P., additional, LaRussa, P., additional, and Bobat, R. A., additional
- Published
- 2017
- Full Text
- View/download PDF
7. Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial: IMPAACT P1041
- Author
-
Zeldow, B., primary, Kim, S., additional, McSherry, G., additional, Cotton, M. F., additional, Jean-Philippe, P., additional, Violari, A., additional, Bobat, R., additional, Nachman, S., additional, Mofenson, L. M., additional, Madhi, S. A., additional, and Mitchell, C., additional
- Published
- 2017
- Full Text
- View/download PDF
8. Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study
- Author
-
Maritz, E. R., primary, Montepiedra, G., additional, Liu, L., additional, Mitchell, C. D., additional, Madhi, S. A., additional, Bobat, R., additional, Violari, A., additional, Ogwu, A., additional, Hesseling, A. C., additional, and Cotton, M. F., additional
- Published
- 2016
- Full Text
- View/download PDF
9. HIV-Associated Tuberculosis in the Newborn and Young Infant
- Author
-
Adhikari, M., Jeena, P., Bobat, R., Archary, M., Naidoo, K., Coutsoudis, A., Singh, R., and Nair, N.
- Subjects
Article Subject - Abstract
Each year, approximately 250 000 women die during pregnancy, delivery, or postpartum. Maternal mortality rates due to tuberculosis (TB) and HIV in Sub-Saharan Africa now supersede obstetric-related causes of mortality. The majority of cases occur in population-dense regions of Africa and Asia where TB is endemic. The vertical transmission rate of tuberculosis is 15%, the overall vertical transmission rate of HIV in resource-limited settings with mono- or dual-ARV therapy varies from 1.9% to 10.7%. If the millennium development goals are to be achieved, both HIV and TB must be prevented. The essential aspect of TB prevention and detection in the newborn is the maternal history and a positive HIV status in the mother. Perinatal outcomes are guarded even with treatment of both diseases. Exclusive breast feeding is recommended. The community and social impact are crippling. The social issues aggravate the prognosis of these two diseases.
- Published
- 2011
- Full Text
- View/download PDF
10. The prevention of mother-to-child HIV transmission programme and infant feeding practices
- Author
-
Coutsoudis A, Rollins N, Adhikari M, Bobat R, and Ruth Bland
- Published
- 2004
11. Nocardia mastoiditis in an African child
- Author
-
Lawler, M., primary, Archary, M., additional, Smith, M., additional, and Bobat, R., additional
- Published
- 2014
- Full Text
- View/download PDF
12. An unusual case of neonatal meningococcal meningitis complicated by subdural empyema and hydrocephalus
- Author
-
Ramsamy, Y, primary, Mahabeer, P, additional, Archary, M, additional, Bobat, R A, additional, and Coovadia, Y M, additional
- Published
- 2013
- Full Text
- View/download PDF
13. Intramedullary conus medullaris tuberculoma in an HIV-infected child: an unusual immune reconstitution inflammatory syndrome response
- Author
-
Lawler, M., primary, Zulu, S., additional, Archary, M., additional, Govender, V., additional, Mubaiwa, L., additional, and Bobat, R., additional
- Published
- 2013
- Full Text
- View/download PDF
14. Age-related pattern of immunoglobulins G, A and M in children born to HIV-seropositive women
- Author
-
Moodley, D., primary, Coovadia, H. M., additional, Bobat, R. A., additional, Gouws, E., additional, and Munsamy, Y., additional
- Published
- 1997
- Full Text
- View/download PDF
15. β2-microglobulin and CD4/CD8 ratio as HIV-1 markers of maternal transmissibility, neonatal infection and disease progression
- Author
-
Moodley, D., primary, Coovadia, H. M., additional, and Bobat, R. A., additional
- Published
- 1996
- Full Text
- View/download PDF
16. The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women.
- Author
-
Coutsoudis, A, primary, Bobat, R A, additional, Coovadia, H M, additional, Kuhn, L, additional, Tsai, W Y, additional, and Stein, Z A, additional
- Published
- 1995
- Full Text
- View/download PDF
17. The effect of lactose-free formula feeds on growth responses among severely malnourished HIV-infected children in Durban, South Africa.
- Author
-
Binka, E., Montoya-Fontalvo, D., Healy, M., Sobieszczyk, M., LaRussa, P., Bobat, R., and Archary, M.
- Subjects
HIV-positive children ,MILK-free diet ,HIV infections ,THERAPEUTICS ,MUCOUS membranes - Abstract
Background. The co-occurrence of HIV infection and severe malnutrition contributes to high rates of morbidity and mortality among children in resource-limited settings. Lactose-free, ready-to-use therapeutic feeds (RUTFs) may be most appropriate in this population because of underlying mucosal damage secondary to inflammation and infection. Objectives. To describe the effect of lactose-free RUTFs on the growth parameters of severely malnourished HIV-infected children in Durban, South Africa (SA). Methods. This was a prospective, observational study of nutritional recovery in HIV-infected, severely malnourished children, aged 6 months to 5 years, who received lactose-free RUTFs following admission to King Edward VIII Hospital in Durban, SA. The primary outcome was nutritional recovery, defined as 15% weight gain from enrolment to end of study. Secondary outcomes included z-scores for weight-for-height, weight-for-age, height-for-age, triceps skinfold thickness (SFT) and subscapular SFT calculated at baseline and 7, 14, 30 and 45 days after admission. Univariate analysis was done to compare outcomes among antiretroviral therapy (ART)-naive and ART-experienced children; the effect of ART on nutritional recovery was evaluated in a logistic regression model. Results. A significant improvement in most nutritional parameters was found at 45 days; 59% of children attained nutritional recovery. There was no significant difference in the proportion of children reaching recovery based on ART status at admission (p=0.08). Conclusion. Lactose-free formula feeds may be an effective strategy for nutritional rehabilitation of severely malnourished and HIV-infected children in resource-limited settings. It remains to be determined how ART initiation affects nutritional recovery in these children. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
18. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.
- Author
-
Bobat R, Coovadia H, Stephen C, Naidoo KL, McKerrow N, Black RE, and Moss WJ
- Published
- 2005
- Full Text
- View/download PDF
19. HIV-1 specific immunoglobulin A antibodies as an effective marker of perinatal infection in developing countries.
- Author
-
Moodley, D., Coovadia, H. M., Bobat, R. A., and Sullivan, J. L.
- Published
- 1997
- Full Text
- View/download PDF
20. The relationship between maternal-infant antibody levels and vertical transmission of HIV-1 infection.
- Author
-
Moodley, D., Coovadia, H. M., Bobat, R. A., Madurai, S., and Sullivan, J. L.
- Published
- 1997
- Full Text
- View/download PDF
21. Early onset meningococcal meningitis.
- Author
-
Bosman, M., Archary, M., Mahabeer, P., and Bobat, R. A.
- Subjects
NEISSERIA meningitidis ,QUALITY of life ,SEPSIS ,SYMPTOMS ,NEWBORN infants - Abstract
Neisseria meningitidis is a rare cause of meningitis and septicaemia in the neonatal population. Meningococcal septicaemia in neonates is divided into early-onset infection (symptoms within seven days of life) and late-onset infection (8-30 days of life). Early-onset meningococcal infection is extremely rare. We report on a case of early-onset meningitis with septicaemia in a term male infant and provide a review of the literature. This case report highlights the importance of maintaining a high index of suspicion of sepsis in the neonate. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
22. VIH et supplémentation en zinc
- Author
-
Bobat, R. and Coovadia, H.
- Published
- 2006
- Full Text
- View/download PDF
23. Use of HIV-1 specific immunoglobulin G3 as a serological marker of vertical transmission.
- Author
-
Madurai, S., Moodley, D., Coovadia, H. M., Bobat, R. A., Gopaul, W., Smith, A. N., and York, D. F.
- Published
- 1996
- Full Text
- View/download PDF
24. Guidance forantiretroviral therapy in HIV-infected infants less than 1 year of age
- Author
-
Cotton, M., Levin, L., Archery, M., Bobat, R., Coovadia, A., Eley, B., Macdonald, P., Meyers, T., Nuttall, J., Helena Rabie, Roux, P., Sherman, G., Tabane, E., and Violari, A.
25. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.
- Author
-
Fowler, M. G., Qin, M., Fiscus, S. A., Currier, J. S., Flynn, P. M., Chipato, T., McIntyre, J., Gnanashanmugam, D., Siberry, G. K., Coletti, A. S., Taha, T. E., Klingman, K. L., Martinson, F. E., Owor, M., Violari, A., Moodley, D., Theron, G. B., Bhosale, R., Bobat, R., and Chi, B. H.
- Subjects
- *
ANTIRETROVIRAL agents , *PERINATALLY-acquired HIV infections , *HIV prevention , *NEVIRAPINE , *AZIDOTHYMIDINE , *HIV infection transmission , *VERTICAL transmission (Communicable diseases) , *LOW birth weight , *BLACK people , *COMBINATION drug therapy , *COMPARATIVE studies , *GESTATIONAL age , *HIV infections , *PREMATURE infants , *INFANT mortality , *MATERNAL health services , *RESEARCH methodology , *EVALUATION of medical care , *MEDICAL cooperation , *PREGNANCY , *RESEARCH , *RESEARCH funding , *EVALUATION research , *RANDOMIZED controlled trials , *CD4 lymphocyte count , *PREVENTION - Abstract
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 .). [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
26. Zinc supplementation in children with HIV-1 infection.
- Author
-
Green JA, Paton NI, Moss WJ, Bobat R, and Black RE
- Published
- 2006
- Full Text
- View/download PDF
27. Community-based approach to HIV treatment.
- Author
-
Pawinski R, Lalloo U, Jinabhai C, and Bobat R
- Published
- 2002
- Full Text
- View/download PDF
28. Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.
- Author
-
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, and Fowler MG
- Subjects
- Humans, Female, Pregnancy, Infant, Newborn, Infant, Adult, India epidemiology, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious drug therapy, Male, Africa epidemiology, Anti-HIV Agents therapeutic use, Young Adult, Breast Feeding, HIV Infections drug therapy, HIV Infections mortality, Premature Birth epidemiology
- Abstract
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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
29. Predictors of TB disease in HIV-exposed children from Southern Africa.
- Author
-
Maritz ER, Montepiedra G, Mitchell CD, Madhi SA, Bobat R, Violari A, Hesseling AC, and Cotton MF
- Subjects
- Infant, Humans, Child, Africa, Southern, South Africa epidemiology, Isoniazid therapeutic use, Tuberculosis epidemiology, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
BACKGROUND: P1041 was a randomised, placebo-controlled isoniazid prophylaxis trial in South Africa. We studied predictors for TB in HIV-exposed children participating in the P1041 trial. METHODS: We included data from entry until Week 108. Predictors considered were type of housing, overcrowding, age, sex, ethnicity, tobacco exposure, weight-for-age percentile Z -score (WAZ), CD4%, viral load (VL), antiretroviral therapy (ART) and number of household smokers. RESULTS: Of 543 HIV-positive (HIV+) and 808 HIV-exposed uninfected (HEU) infants at entry, median age was 96 days (interquartile range: 92-105). Of 1,351 caregivers, 125 (9%) had a smoking history, and 62/1,351 reported current smoking. In 594/1,351 (44%) households, there was at least one smoker. Smoking caregivers consumed 1-5 cigarettes daily. In the HIV+ cohort, significant baseline TB predictors after adjusting covariates were as follows: WAZ (adjusted hazard ratio [aHR] 0.76, P = 0.002) and log
10 HIV RNA copies/ml (aHR 1.50, P = 0.009). Higher CD4% (aHR 0.88, P = 0.002) and ART (aHR 0.50, P = 0.006) were protective. In the HEU cohort, smoking exposure was associated with reduced TB-free survival on univariate analysis, but not after adjustment in the multivariate model. CONCLUSION: Low WAZ and high VL were strong predictors of TB disease or death. Rising CD4 percentage and being on ART were protective in the HIV+ cohort.- Published
- 2023
- Full Text
- View/download PDF
30. Association of Maternal Viral Load and CD4 Count With Perinatal HIV-1 Transmission Risk During Breastfeeding in the PROMISE Postpartum Component.
- Author
-
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, and Shapiro DE
- Subjects
- Anti-HIV Agents adverse effects, CD4 Lymphocyte Count, Female, HIV Infections drug therapy, HIV Infections prevention & control, HIV Seropositivity drug therapy, HIV-1, Humans, Infant, Peripartum Period, Postpartum Period, Pregnancy, Treatment Outcome, Anti-HIV Agents therapeutic use, Breast Feeding, HIV Infections transmission, Infectious Disease Transmission, Vertical prevention & control, Nevirapine therapeutic use, Viral Load drug effects
- Abstract
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., Competing Interests: P.M.F. is a consultant for Merck. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
31. Viral hepatitis B and C in HIV-exposed South African infants.
- Author
-
Tamandjou Tchuem C, Cotton MF, Nel E, Tedder R, Preiser W, Violari A, Bobat R, Hovind L, Aaron L, Montepiedra G, Mitchell C, and Andersson MI
- Subjects
- Child, DNA, Viral genetics, Female, Hepatitis B virus genetics, Humans, Infant, Infectious Disease Transmission, Vertical prevention & control, Phylogeny, Pregnancy, South Africa epidemiology, HIV Infections complications, HIV Infections epidemiology, Hepatitis B diagnosis, Hepatitis B epidemiology, Pregnancy Complications, Infectious
- Abstract
Background: Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa., Methods: Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing., Results: Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive., Conclusions: This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.
- Published
- 2020
- Full Text
- View/download PDF
32. Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir.
- Author
-
Rabie H, Tikiso T, Lee J, Fairlie L, Strehlau R, Bobat R, Liberty A, McIlleron H, Andrieux-Meyer I, Cotton M, Lallemant M, and Denti P
- Subjects
- Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, Antitubercular Agents pharmacokinetics, Antitubercular Agents therapeutic use, Biological Availability, Child, Child, Preschool, Dideoxynucleosides therapeutic use, Drug Combinations, Drug Interactions, Humans, Lopinavir therapeutic use, Prospective Studies, Rifampin therapeutic use, Ritonavir therapeutic use, Dideoxynucleosides pharmacokinetics, HIV Infections drug therapy, Lopinavir pharmacokinetics, Rifampin pharmacokinetics, Ritonavir pharmacokinetics, Tuberculosis, Pulmonary drug therapy
- Abstract
In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.)., (Copyright © 2020 Rabie et al.)
- Published
- 2020
- Full Text
- View/download PDF
33. Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus-infected children in relation to treatment outcomes.
- Author
-
Archary M, Mcllleron H, Bobat R, LaRussa P, Sibaya T, Wiesner L, and Hennig S
- Subjects
- Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Biological Availability, Body Weight, Child, Child Nutrition Disorders diagnosis, Child Nutrition Disorders etiology, Child Nutrition Disorders rehabilitation, Child, Preschool, Dideoxynucleosides administration & dosage, Dideoxynucleosides adverse effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Dosage Calculations, Female, Follow-Up Studies, HIV isolation & purification, HIV Infections blood, HIV Infections complications, HIV Infections mortality, Humans, Infant, Lamivudine administration & dosage, Lamivudine adverse effects, Male, Models, Biological, Nutritional Support, Severity of Illness Index, South Africa epidemiology, Time Factors, Time-to-Treatment, Treatment Outcome, Viral Load, Anti-HIV Agents pharmacokinetics, Child Nutrition Disorders metabolism, Dideoxynucleosides pharmacokinetics, HIV Infections drug therapy, Lamivudine pharmacokinetics
- Abstract
Aims: Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished paediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment., Methods: Severely malnourished human immunodeficiency virus-infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using World Health Organization weight-band dosages. Abacavir and lamivudine concentrations were measured as a secondary objective on day 1 and day 14 and patients were followed-up to week 48. Population PK of abacavir and lamivudine were described using NONMEM., Results: In total, 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1-10.8 (median 1.4) years. Abacavir PK was described by a 2-compartment model, patients randomized to early ART showed increased bioavailability of 31%. Apparent clearance (CL/F, L/h/7 kg) of abacavir increased from day 1 to day 14 from 3.33 (95% confidence interval 2.71-4.12) to 5.86 (95% confidence interval 4.78-7.3). A 1-compartment model described lamivudine PK, variability on CL/F was explained by maturation with age, with age at half-matured CL/F being 4 months. For both drugs allometrically scaled total body weight was related to CL/F and apparent volume of distribution. PK exposure did not correlate with virological outcomes or death at 12 or 48 weeks., Conclusion: Increases in Abacavir's CL/F between day 1 to day 14, bioavailability and PK variability with early start of ART was found in this cohort of severely malnourished children; however, these changes did not influence virological outcomes. The study supports the use of weight-band dosage tables., (© 2019 The British Pharmacological Society.)
- Published
- 2019
- Full Text
- View/download PDF
34. A prospective study of the immune reconstitution inflammatory syndrome (IRIS) in HIV-infected children from high prevalence countries.
- Author
-
Cotton MF, Rabie H, Nemes E, Mujuru H, Bobat R, Njau B, Violari A, Mave V, Mitchell C, Oleske J, Zimmer B, Varghese G, and Pahwa S
- Subjects
- Africa South of the Sahara epidemiology, Child, Preschool, Cryptococcus immunology, Cytomegalovirus immunology, Female, HIV-1 immunology, Humans, Incidence, India epidemiology, Infant, Male, Prevalence, Prospective Studies, Colitis epidemiology, Colitis immunology, Cytomegalovirus Infections epidemiology, Cytomegalovirus Infections immunology, HIV Infections epidemiology, HIV Infections immunology, Immune Reconstitution Inflammatory Syndrome epidemiology, Immune Reconstitution Inflammatory Syndrome immunology, Meningitis, Cryptococcal epidemiology, Meningitis, Cryptococcal immunology
- Abstract
Background: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected infants and young children is relatively understudied in regions endemic for HIV and TB. We aimed to describe incidence, clinical features and risk factors of pediatric IRIS in Sub-Saharan Africa and India., Methods and Findings: We conducted an observational multi-centred prospective clinical study from December 2010 to September 2013 in children <72 months of age recruited from public antiretroviral programs. The main diagnostic criterion for IRIS was a new or worsening inflammatory event after initiating antiretroviral therapy (ART). Among 198 participants, median age 1.15 (0.48; 2.21) years, 38 children (18.8%) developed 45 episodes of IRIS. Five participants (13.2%) had two IRIS events and one (2.6%) had 3 events. Main causes of IRIS were BCG (n = 21; 46.7%), tuberculosis (n = 10; 22.2%) and dermatological, (n = 8, 17.8%). Four TB IRIS cases had severe morbidity including 1 fatality. Cytomegalovirus colitis and cryptococcal meningitis IRIS were also severe. BCG IRIS resolved without pharmacological intervention. On multivariate logistic regression, the most important baseline associations with IRIS were high HIV viral load (likelihood ratio [LR] 10.629; p = 0.0011), recruitment at 1 site (Stellenbosch University) (LR 4.01; p = 0.0452) and CD4 depletion (LR 3.4; p = 0.0654). Significantly more non-IRIS infectious and inflammatory events between days 4 and 17 of ART initiation were noted in cases versus controls (35% versus 15.2%: p = 0.0007)., Conclusions: IRIS occurs commonly in HIV-infected children initiating ART and occasionally has severe morbidity. The incidence may be underestimated. Predictive, diagnostic and prognostic biomarkers are needed., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
- Full Text
- View/download PDF
35. Population Pharmacokinetics of Lopinavir in Severely Malnourished HIV-infected Children and the Effect on Treatment Outcomes.
- Author
-
Archary M, Mcllleron H, Bobat R, La Russa P, Sibaya T, Wiesner L, and Hennig S
- Subjects
- Antiretroviral Therapy, Highly Active methods, Body Mass Index, Child, Child, Preschool, Female, HIV Infections complications, HIV Protease Inhibitors administration & dosage, Humans, Infant, Lopinavir administration & dosage, Male, Plasma chemistry, Treatment Outcome, HIV Infections drug therapy, HIV Protease Inhibitors pharmacokinetics, Lopinavir pharmacokinetics, Malnutrition
- Abstract
Background: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiologic changes because of malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs., Methods: HIV-infected children admitted with severe acute malnutrition were randomized to early or delayed initiation of lopinavir (LPV)/ritonavir, abacavir and lamivudine using World Health Organization weight band dosage charts. LPV concentrations were measured on day 1 and day 14. Thereafter, patients were followed-up to week 48. The population pharmacokinetics of LPV was described using NONMEM v7.3. Covariates were screened to assess their influence on the pharmacokinetics of LPV, and the relationship between pharmacokinetic variability and treatment outcomes were assessed., Results: Five hundred and two LPV concentrations were collected from 62 pediatric patients 0.1-3.9 years of age (median: 0.9 years). Rifampin-based antituberculosis treatment and "super-boosted" LPV/ritonavir were prescribed in 20 patients. LPV disposition was well described by a one-compartment model with first-order elimination. Neither randomization to early or delayed ART, tuberculosis comedications nor anthropometrical measurements explained the pharmcokinetic variability. Allometrically scaled fat-free mass influenced apparent clearance (CL/F) and volume of distribution (Vd/F). Pharmacokinetic exposure did not correlate with virologic outcomes or death at 12 or 48 weeks., Conclusions: LPV pharmacokinetics was influenced by fat-free mass and not by timing of ART initiation or tuberculosis comedication in severely malnourished HIV-infected children. LPV pharmacokinetics was found to be highly variable and bioavailability greatly reduced, resulting in a high CL estimate in this population. The role of LPV dose adjustment should be further evaluated in severely malnourished children initiating ART.
- Published
- 2018
- Full Text
- View/download PDF
36. 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.
- Author
-
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, and Shapiro DE
- Subjects
- Africa South of the Sahara, Child, Preschool, Female, HIV Infections drug therapy, HIV Infections pathology, Humans, India, Infant, Infant, Newborn, Postpartum Period, Treatment Outcome, Anti-HIV Agents therapeutic use, Breast Feeding, Chemoprevention methods, HIV Infections prevention & control, HIV Infections transmission, Infectious Disease Transmission, Vertical prevention & control
- Abstract
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.
- Published
- 2018
- Full Text
- View/download PDF
37. Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy.
- Author
-
Muenchhoff M, Healy M, Singh R, Roider J, Groll A, Kindra C, Sibaya T, Moonsamy A, McGregor C, Phan MQ, Palma A, Kloverpris H, Leslie A, Bobat R, LaRussa P, Ndung'u T, Goulder P, Sobieszczyk ME, and Archary M
- Subjects
- Acute Disease, Bacterial Translocation, Biomarkers blood, CD4 Lymphocyte Count, Child, Child, Preschool, Cross-Sectional Studies, Female, Flow Cytometry, HIV Infections complications, HIV-1, Humans, Infant, Lymphocyte Activation, Male, Malnutrition immunology, Severity of Illness Index, Treatment Outcome, Viral Load, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Malnutrition virology
- Abstract
This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART.
- Published
- 2018
- Full Text
- View/download PDF
38. Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.
- Author
-
Gupta A, Montepiedra G, Gupte A, Zeldow B, Jubulis J, Detrick B, Violari A, Madhi S, Bobat R, Cotton M, Mitchell C, and Spector S
- Subjects
- Adult, Anoctamins, Cohort Studies, Female, Follow-Up Studies, Gene Expression, Genetic Predisposition to Disease, HIV Infections complications, HIV Infections immunology, HIV Infections mortality, Humans, Infant, Male, Membrane Proteins immunology, Phospholipid Transfer Proteins, Plakophilins immunology, Polymorphism, Single Nucleotide, Real-Time Polymerase Chain Reaction, Receptors, Calcitriol genetics, Receptors, Calcitriol immunology, Receptors, Interleukin-1 genetics, Receptors, Interleukin-1 immunology, Survival Analysis, Tuberculosis, Pulmonary complications, Tuberculosis, Pulmonary immunology, Tuberculosis, Pulmonary mortality, Vitamin D blood, Vitamin D immunology, Vitamin D Deficiency complications, Vitamin D Deficiency immunology, Vitamin D Deficiency mortality, Vitamin D-Binding Protein genetics, Vitamin D-Binding Protein immunology, HIV Infections genetics, Membrane Proteins genetics, Plakophilins genetics, Tuberculosis, Pulmonary genetics, Vitamin D analogs & derivatives, Vitamin D Deficiency genetics
- Abstract
Background: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children., Methods: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed., Findings: Median age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01-3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03-3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs., Conclusions: Two novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child's risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial., Trial Registration: ClinicalTrials.gov NCT00080119.
- Published
- 2016
- Full Text
- View/download PDF
39. An update on the HIV treatment cascade in children and adolescents.
- Author
-
Bobat R, Archary M, and Lawler M
- Subjects
- Adolescent, Africa, Asia, Child, Early Diagnosis, Humans, Medication Adherence, Secondary Prevention, Anti-Retroviral Agents therapeutic use, HIV Infections diagnosis, HIV Infections drug therapy
- Abstract
Purpose of Review: To provide an update on the HIV treatment cascade in children and adolescents. We reviewed the literature on the steps in the cascade, for the period 2014-2015., Recent Findings: There remains high attrition of children with regards to early testing and linking those patients who are positive to early treatment. Barriers to screening and testing in children and adolescents are multifactorial. Linkage to pre-antiretroviral therapy care and retention in care are the main steps at which attrition occurs. There are a number of new formulations available for use in adolescents and children which offer more options for antiretroviral therapy treatment. Adherence levels appear to be reasonable in Africa and Asia; however, achieving viral load suppression remains a challenge., Summary: We have a long way to go to achieve decreased attrition at each step of the cascade and retain patients in care. Recent improvements in each step of the cascade are bringing us closer to achieving treatment success.
- Published
- 2015
- Full Text
- View/download PDF
40. Donovanosis causing lymphadenitis, mastoiditis, and meningitis in a child.
- Author
-
Ahmed N, Pillay A, Lawler M, Bobat R, and Archary M
- Subjects
- Azithromycin therapeutic use, Female, Granuloma Inguinale drug therapy, Granuloma Inguinale transmission, Humans, Infant, Infectious Disease Transmission, Vertical, Granuloma Inguinale complications, Granuloma Inguinale diagnosis, Lymphadenitis etiology, Mastoiditis etiology, Meningitis etiology
- Published
- 2015
- Full Text
- View/download PDF
41. Predictors of virologic and clinical response to nevirapine versus lopinavir/ritonavir-based antiretroviral therapy in young children with and without prior nevirapine exposure for the prevention of mother-to-child HIV transmission.
- Author
-
Lindsey JC, Hughes MD, Violari A, Eshleman SH, Abrams EJ, Bwakura-Dangarembizi M, Barlow-Mosha L, Kamthunzi P, Sambo PM, Cotton MF, Moultrie H, Khadse S, Schimana W, Bobat R, Zimmer B, Petzold E, Mofenson LM, Jean-Philippe P, and Palumbo P
- Subjects
- Africa South of the Sahara epidemiology, Child, Preschool, Female, HIV Infections epidemiology, HIV Infections virology, Humans, Incidence, India epidemiology, Infant, Infant, Newborn, Male, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 isolation & purification, Infectious Disease Transmission, Vertical prevention & control, Lopinavir therapeutic use, Nevirapine therapeutic use, Ritonavir therapeutic use
- Abstract
Background: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates., Methods: Efficacy was assessed by time to ART discontinuation or virologic failure, virologic failure/death and death; safety by time to ART discontinuation because of a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height World Health Organization z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates., Results: Over a median follow up of 48 (PrNVP) and 72 (no PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r-based ART was superior to NVP-based ART for efficacy and safety outcomes; however, those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pretreatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pretreatment CD4% with shorter time to ART discontinuation because of a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥ 3 adverse event., Conclusions: Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breast-feeding, sex, HIV-1 subtype, age, pretreatment CD4%, HIV-1 RNA or World Health Organization disease stage. This finding should be considered when selecting an ART regimen for young children.
- Published
- 2014
- Full Text
- View/download PDF
42. Loss to follow-up among infants in a study of isoniazid prophylaxis (P1041) in South Africa.
- Author
-
Beneri CA, Zeldow B, Nachman S, Van der Linde M, Pillay E, Dittmer S, Kim S, Jean-Philippe P, Coetzee J, Bobat R, Hawkins E, and Violari A
- Subjects
- Double-Blind Method, Female, Follow-Up Studies, HIV Infections complications, Humans, Infant, Male, Risk Factors, South Africa, Tuberculosis etiology, Antitubercular Agents therapeutic use, Isoniazid therapeutic use, Patient Compliance statistics & numerical data, Tuberculosis prevention & control
- Abstract
Objective: To assess risk factors for loss to follow-up (LFU) from the IMPAACT P1041 study, an isoniazid (INH) prophylaxis study conducted in southern Africa., Design: Infants in two cohorts, human immunodeficiency virus-infected (HIV+) and HIV-exposed but non-infected (HIV-), were randomized to INH or placebo for 96 weeks. LFU was evaluated at week 96., Results: Of 1351 infants, 12.9% were LFU (10.4% HIV+, 14.7% HIV-); 65% of the HIV+ cohort was asymptomatic. Among HIV+ infants, large household size (>6 vs. <4 members, P = 0.035) and presence of an elder (≥55 years, P = 0.05) were associated with better retention. Although attenuated in adjusted analysis, these associations held among HIV- infants. Among HIV- infants, having a younger mother increased the risk (P = 0.008) and maternal history of TB reduced the risk of LFU, the latter by nearly 70% (P = 0.048 univariate, 0.09 adjusted). LFU was largely due to inability to contact the participant (58% HIV+, 30% HIV-), and inability to attend the clinic and withdrawal of consent (HIV-)., Conclusions: Household support was an important factor in participant retention, particularly for the non-HIV-infected cohort, as young maternal age was a risk factor for LFU. Retaining study participants from this mobile population can be challenging and may warrant additional support.
- Published
- 2013
- Full Text
- View/download PDF
43. Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants.
- Author
-
Kiser JJ, Zhu R, DʼArgenio DZ, Cotton MF, Bobat R, McSherry GD, Madhi SA, Carey VJ, Seifart HI, Werely CJ, and Fletcher CV
- Subjects
- Area Under Curve, Child, Preschool, Double-Blind Method, Female, HIV Infections metabolism, HIV Infections microbiology, Humans, Infant, Male, Mycobacterium tuberculosis isolation & purification, South Africa, Tuberculosis microbiology, Tuberculosis prevention & control, Tuberculosis virology, Antitubercular Agents pharmacokinetics, Antitubercular Agents therapeutic use, Isoniazid pharmacokinetics, Isoniazid therapeutic use, Tuberculosis drug therapy
- Abstract
Aims: There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing., Methods: Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L., Results: In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L., Conclusions: INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L.
- Published
- 2012
- Full Text
- View/download PDF
44. Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children.
- Author
-
Violari A, Lindsey JC, Hughes MD, Mujuru HA, Barlow-Mosha L, Kamthunzi P, Chi BH, Cotton MF, Moultrie H, Khadse S, Schimana W, Bobat R, Purdue L, Eshleman SH, Abrams EJ, Millar L, Petzold E, Mofenson LM, Jean-Philippe P, and Palumbo P
- Subjects
- Anti-Retroviral Agents adverse effects, CD4 Lymphocyte Count, Child, Preschool, Drug Therapy, Combination adverse effects, Female, HIV Infections mortality, Humans, Infant, Kaplan-Meier Estimate, Lamivudine adverse effects, Lopinavir adverse effects, Male, Nevirapine adverse effects, Nevirapine therapeutic use, RNA, Viral blood, Ritonavir adverse effects, Ritonavir therapeutic use, Zidovudine adverse effects, Anti-Retroviral Agents therapeutic use, HIV Infections prevention & control, HIV-1, Lamivudine therapeutic use, Lopinavir therapeutic use, Zidovudine therapeutic use
- Abstract
Background: Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established., Methods: In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24., Results: A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06)., Conclusions: Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.).
- Published
- 2012
- Full Text
- View/download PDF
45. Drug resistance and coreceptor usage in HIV type 1 subtype C-infected children initiating or failing highly active antiretroviral therapy in South Africa.
- Author
-
Green TN, Archary M, Gordon ML, Padayachi N, Lie Y, Anton ED, Reeves JD, Grobler A, Bobat R, Coovadia H, and Ndung'u T
- Subjects
- CCR5 Receptor Antagonists, CD4 Lymphocyte Count, Child, Child, Preschool, Female, HIV Seropositivity genetics, HIV Seropositivity virology, Humans, Logistic Models, Male, Maraviroc, Medication Adherence statistics & numerical data, Multivariate Analysis, Phylogeny, Predictive Value of Tests, Receptors, CXCR4 isolation & purification, Sensitivity and Specificity, South Africa epidemiology, Treatment Failure, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active, Cyclohexanes administration & dosage, Drug Resistance, Viral genetics, HIV Seropositivity drug therapy, HIV-1 genetics, Receptors, HIV drug effects, Triazoles administration & dosage
- Abstract
HIV-1 drug resistance monitoring in resource-poor settings is crucial due to limited drug alternatives. Recent reports of the increased prevalence of CXCR4 usage in subtype C infections may have implications for CCR5 antagonists in therapy. We investigated the prevalence of drug resistance mutations and CXCR4 coreceptor utilization of viruses from HIV-1 subtype C-infected children. Fifty-one children with virological failure during highly active antiretroviral therapy (HAART) and 43 HAART-naive children were recruited. Drug resistance genotyping and coreceptor utilization assessment by phenotypic and genotypic methods were performed. At least one significant drug resistance mutation was present in 85.4% of HAART-failing children. Thymidine analogue mutations (TAMs) were detected in 58.5% of HAART-failing children and 39.0% had ≥3 TAMs. CXCR4 (X4) or dual (R5X4)/mixed (R5, X4) (D/M)-tropic viruses were found in 54.3% of HAART-failing and 9.4% of HAART-naive children (p<0.0001); however, the HAART-failing children were significantly older (p<0.0001). In multivariate logistic regression, significant predictors of CXCR4 usage included antiretroviral treatment, older age, and lower percent CD4(+) T cell counts. The majority of genotypic prediction tools had low sensitivity (≤65.0%) and high specificity (≥87.5%) for predicting CXCR4 usage. Extensive drug resistance, including the high percentage of TAMs found, may compromise future drug choices for children, highlighting the need for improved treatment monitoring and adherence counseling. Additionally, the increased prevalence of X4/D/M viruses in HAART-failing children suggests limited use of CCR5 antagonists in salvage therapy. Enhanced genotypic prediction tools are needed as current tools are not sensitive enough for predicting CXCR4 usage.
- Published
- 2012
- Full Text
- View/download PDF
46. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.
- Author
-
Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, Jean-Philippe P, McSherry G, and Mitchell C
- Subjects
- Antitubercular Agents adverse effects, Double-Blind Method, Drug Resistance, Bacterial, Female, Follow-Up Studies, Humans, Infant, Intention to Treat Analysis, Isoniazid adverse effects, Kaplan-Meier Estimate, Male, Tuberculosis diagnosis, Viral Load, AIDS-Related Opportunistic Infections prevention & control, Antitubercular Agents therapeutic use, HIV Infections drug therapy, HIV-1, Isoniazid therapeutic use, Tuberculosis prevention & control
- Abstract
Background: The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period., Methods: We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization., Results: Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups., Conclusions: Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).
- Published
- 2011
- Full Text
- View/download PDF
47. Antiretroviral treatment for children with peripartum nevirapine exposure.
- Author
-
Palumbo P, Lindsey JC, Hughes MD, Cotton MF, Bobat R, Meyers T, Bwakura-Dangarembizi M, Chi BH, Musoke P, Kamthunzi P, Schimana W, Purdue L, Eshleman SH, Abrams EJ, Millar L, Petzold E, Mofenson LM, Jean-Philippe P, and Violari A
- Subjects
- Anti-HIV Agents administration & dosage, Child, Preschool, Drug Therapy, Combination, Female, HIV Infections mortality, HIV Infections prevention & control, HIV Infections transmission, Humans, Infant, Infant, Newborn, Infectious Disease Transmission, Vertical prevention & control, Kaplan-Meier Estimate, Lopinavir, Male, Pregnancy, Pregnancy Complications, Infectious drug therapy, Pyrimidinones therapeutic use, RNA, Viral blood, Ritonavir therapeutic use, Treatment Failure, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV-1 genetics, HIV-1 isolation & purification, Nevirapine administration & dosage
- Abstract
Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown., Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board., Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events., Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.).
- Published
- 2010
- Full Text
- View/download PDF
48. Use of abacavir in 30 HIV-infected children from Durban, South Africa: report from a pilot study.
- Author
-
Bobat R, Kindra G, Kiepiela P, Reddy S, Jeena PM, Adhikari M, and Coovadia HM
- Subjects
- Child, Child, Preschool, Humans, Pilot Projects, South Africa, Treatment Outcome, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, Dideoxynucleosides therapeutic use, HIV Infections drug therapy
- Published
- 2010
- Full Text
- View/download PDF
49. Human immunodeficiency virus-specific CD8+ T-cell activity is detectable from birth in the majority of in utero-infected infants.
- Author
-
Thobakgale CF, Ramduth D, Reddy S, Mkhwanazi N, de Pierres C, Moodley E, Mphatswe W, Blanckenberg N, Cengimbo A, Prendergast A, Tudor-Williams G, Dong K, Jeena P, Kindra G, Bobat R, Coovadia H, Kiepiela P, Walker BD, and Goulder PJ
- Subjects
- Africa South of the Sahara, CD4-Positive T-Lymphocytes immunology, Female, HIV immunology, Humans, Infant, Infant, Newborn, Infectious Disease Transmission, Vertical, Interferons biosynthesis, Male, Pregnancy, Pregnancy Complications, Infectious, gag Gene Products, Human Immunodeficiency Virus immunology, nef Gene Products, Human Immunodeficiency Virus immunology, pol Gene Products, Human Immunodeficiency Virus immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections congenital, HIV Infections immunology, T-Lymphocyte Subsets immunology
- Abstract
Human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa typically progress to AIDS or death by 2 years of life in the absence of antiretroviral therapy. This rapid progression to HIV disease has been related to immaturity of the adaptive immune response in infants. We screened 740 infants born to HIV-infected mothers and tracked development and specificity of HIV-specific CD8+ T-cell responses in 63 HIV-infected infants identified using gamma interferon enzyme-linked immunospot assays and intracellular cytokine staining. Forty-four in utero-infected and 19 intrapartum-infected infants were compared to 45 chronically infected children >2 years of age. Seventy percent (14 of 20) in utero-infected infants tested within the first week of life demonstrated HIV-specific CD8+ T-cell responses. Gag, Pol, and Nef were the principally targeted regions in chronic pediatric infection. However, Env dominated the overall response in one-third (12/36) of the acutely infected infants, compared to only 2/45 (4%) of chronically infected children (P = 0.00083). Gag-specific CD4+ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virus-specific CD8+ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants.
- Published
- 2007
- Full Text
- View/download PDF
50. Multidrug-resistant tuberculous meningitis in children in Durban, South Africa.
- Author
-
Padayatchi N, Bamber S, Dawood H, and Bobat R
- Subjects
- Antitubercular Agents pharmacology, Antitubercular Agents therapeutic use, Cerebrospinal Fluid microbiology, Child, Child, Preschool, Drug Resistance, Multiple, Bacterial, Female, HIV Infections complications, Humans, Infant, Male, Microbial Sensitivity Tests, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Retrospective Studies, South Africa, Tuberculosis, Meningeal diagnosis, Tuberculosis, Meningeal microbiology, Tuberculosis, Meningeal mortality, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Multidrug-Resistant mortality
- Abstract
Background: Tuberculous meningitis (TBM) is the most frequent manifestation of central nervous system tuberculosis (TB) and is more common in children than in adults. The diagnosis of TBM in children is difficult because signs and symptoms are vague. Information about drug resistant TB in children is scarce, and there is no published information on drug resistant TBM in children., Methods: This is a retrospective review of medical records of children with culture-confirmed multidrug-resistant tuberculous meningitis (MDR-TBM) at King George V Hospital in Durban, South Africa., Results: Between 1992 and 2003, there were 8 children with MDR-TBM; 6 were HIV infected and 2 were HIV negative. Only one child survived. The diagnosis was made posthumously in almost all the children., Discussion: The changes in the cerebrospinal fluid (CSF) in early TBM can be nonspecific and can change rapidly; therefore, CSF studies should always include culture and susceptibility testing. Factors that contributed to the high mortality were disseminated TB, HIV infection, delay in diagnosis and treatment, the absence of a standardized approach to the management of MDR-TBM and the poor CSF penetration of most MDR-TB drugs. MDR-TB therapy should be considered if there is a history of TB: a MDR-TB contact or a poor clinical response to TB therapy despite adequate adherence to treatment. Early diagnosis is important because TBM in children is often associated with a grave outcome.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.