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1.  Impact of Maternal and Infant Antiretroviral Drug Regimens on Drug Resistance in HIV-Infected Breastfeeding Infants 
The Pediatric infectious disease journal  2013;32(4):10.1097/INF.0b013e31827f44ee.
BACKGROUND
The HPTN 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV-infection despite prophylaxis.
METHODS
HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher’s exact tests were used to evaluate associations between categorical variables.
RESULTS
NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in seven (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8=75% in the NVP arm, 1/17=5.9% in the placebo arm, P=0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral (ARV) treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all four of those infants by 6 months of age (4/4=100%). In contrast, only three (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate ARV treatment developed NVP resistance (P=0.003).
CONCLUSIONS
Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
doi:10.1097/INF.0b013e31827f44ee
PMCID: PMC3826537  PMID: 23249916
Nevirapine resistance; prevention of mother-to-child transmission; extended nevirapine; HIV
2.  Morbidity and Mortality Among a Cohort of Human Immunodeficiency Virus Type 1-Infected and Uninfected Pregnant Women and Their Infants From Malawi, Zambia, and Tanzania 
Background:
Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions.
Methods:
Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling.
Results:
Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4 – 6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses.
Conclusions:
The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.
doi:10.1097/INF.0b013e31817109a4
PMCID: PMC2739309  PMID: 18679152
HIV-1 infection; infant mortality; maternal morbidity and mortality; sub-Saharan Africa; pregnant women

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