Dataset Information

Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting: The Breastfeeding, Antiretrovirals and Nutrition Study.

ABSTRACT: BACKGROUND:To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission (MTCT) of HIV in women unexposed to antiretroviral therapy (ART) during pregnancy. METHODS:We compared factors according to perinatal MTCT outcome among 2275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression. RESULTS:There were 119 (115 intrauterine and 4 intrapartum) cases of perinatal MTCT, only one to a mother with <1000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1000 copies/mL and 1000.1-10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI): 0.01-0.4 and aOR, 0.2; 95% CI: 0.1-0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (?350 cells/?L) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI: 1.2-2.6), sexually transmitted infection (STI) (past year; aOR, 1.9; 95% CI: 1.0-3.7), histories of herpes zoster (aOR, 3.0; 95% CI: 1.6-5.6) and tuberculosis (aOR, 2.5; 95% CI: 1.1-5.7) were associated with increased odds of perinatal MTCT. CONCLUSIONS:These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT and support efforts to address food shortage, STI and tuberculosis prevention, while informing programs to improve ART coverage in pregnancy.

SUBMITTER: Ewing AC

PROVIDER: S-EPMC6481191 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting: The Breastfeeding, Antiretrovirals and Nutrition Study.

Ewing Alexander C AC Ellington Sascha R SR Wiener Jeffrey B JB Chasela Charles S CS Tegha Gerald G Nelson Julie A E JAE Jamieson Denise J DJ van der Horst Charles C Kourtis Athena P AP

The Pediatric infectious disease journal 20190501 5

<h4>Background</h4>To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission (MTCT) of HIV in women unexposed to antiretroviral therapy (ART) during pregnancy.<h4>Methods</h4>We compared factors according to perinatal MTCT outcome among 2275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food se ...[more]

PMID: 30985546

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Project description:BackgroundThe free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART.Methods and findingsThis cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/μL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001).ConclusionThe option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.

Project description:ImportanceThe overwhelming majority of fetal and neonatal deaths occur in low- and middle-income countries. Fetal and neonatal risk assessment tools may be useful to predict the risk of death.ObjectiveTo develop risk prediction models for intrapartum stillbirth and neonatal death.Design, setting, and participantsThis cohort study used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research population-based vital registry, including clinical sites in South Asia (India and Pakistan), Africa (Democratic Republic of Congo, Zambia, and Kenya), and Latin America (Guatemala). A total of 502 648 pregnancies were prospectively enrolled in the registry.ExposuresRisk factors were added sequentially into the data set in 4 scenarios: (1) prenatal, (2) predelivery, (3) delivery and day 1, and (4) postdelivery through day 2.Main outcomes and measuresData sets were randomly divided into 10 groups of 3 analysis data sets including training (60%), test (20%), and validation (20%). Conventional and advanced machine learning modeling techniques were applied to assess predictive abilities using area under the curve (AUC) for intrapartum stillbirth and neonatal mortality.ResultsAll prenatal and predelivery models had predictive accuracy for both intrapartum stillbirth and neonatal mortality with AUC values 0.71 or less. Five of 6 models for neonatal mortality based on delivery/day 1 and postdelivery/day 2 had increased predictive accuracy with AUC values greater than 0.80. Birth weight was the most important predictor for neonatal death in both postdelivery scenarios with independent predictive ability with AUC values of 0.78 and 0.76, respectively. The addition of 4 other top predictors increased AUC to 0.83 and 0.87 for the postdelivery scenarios, respectively.Conclusions and relevanceModels based on prenatal or predelivery data had predictive accuracy for intrapartum stillbirths and neonatal mortality of AUC values 0.71 or less. Models that incorporated delivery data had good predictive accuracy for risk of neonatal mortality. Birth weight was the most important predictor for neonatal mortality.

Project description:BackgroundThe results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years.ObjectiveTo inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials.DesignCost-effectiveness analysis by using a computer simulation model of HIV disease.Data sourcesPublished data from randomized trials and observational cohorts in South Africa.Target populationHIV-infected patients in South Africa.Time horizon5-year and lifetime.PerspectiveModified societal.InterventionNo treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L.Outcome measuresMorbidity, mortality, life expectancy, medical costs, and cost-effectiveness.Results of base-case analysisIf 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved.Results of sensitivity analysisInitiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%.LimitationThis model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission.ConclusionEarlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended.Primary funding sourceNational Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Project description:BACKGROUND:Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. METHODS:We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m(2)), moderate (16.00-16.99 kg/m(2)), and mild (17.00-18.49 kg/m(2)) malnutrition categories. RESULTS:19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m(2) category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m(2) patients. Among BMI 17.00-18.49 kg/m(2) patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. CONCLUSIONS:Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.

Dataset Information

Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting: The Breastfeeding, Antiretrovirals and Nutrition Study.

Publications

Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting: The Breastfeeding, Antiretrovirals and Nutrition Study.

Similar Datasets

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