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The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV.

ABSTRACT: BACKGROUND:The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning. METHOD:A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counseling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence. RESULTS:The proportion of mother-to-child transmission (MTCT) from mothers who seroconverted after their first antenatal visit was 26% [95% confidence interval (CI): 22% to 30%] in 2008, or 15,000 of 57,000 infections. It is estimated that by 2014, total MTCT will reduce to 39,000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13,000 per annum, accounting for 34% (95% CI: 29% to 39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010-2015 period would reduce by 28% (95% CI: 25% to 31%), from 39,000 to 28,000 per annum. CONCLUSION:Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the pediatric HIV burden and needs greater attention in the planning of prevention of MTCT programs.

SUBMITTER: Johnson LF

PROVIDER: S-EPMC3378499 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV.

Johnson Leigh F LF Stinson Kathryn K Newell Marie-Louise ML Bland Ruth M RM Moultrie Harry H Davies Mary-Ann MA Rehle Thomas M TM Dorrington Rob E RE Sherman Gayle G GG

Journal of acquired immune deficiency syndromes (1999) 20120401 4

<h4>Background</h4>The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning.<h4>Method</h4>A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant ...[more]

PMID: 22193774

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Project description:BackgroundMother-to-child transmission of HIV (MTCT) depends on the timing of HIV infection. We estimated HIV-seroconversion during pregnancy (HSP) after having a HIV-negative result antenatally, and its contribution to early MTCT in South Africa (SA).Methods and findingsBetween August 2011 and March 2012, we recruited a nationally representative sample of mother-infant pairs with infants aged 4-to-8 weeks from 578 health facilities. Data collection included mother interviews, child health-card reviews, and infant dried-blood-spots sample (iDBS). iDBS were tested for HIV antibodies and HIV-deoxyribonucleic-acid (HIV-DNA). HSP was defined as maternal self-report of an HIV-negative test during this pregnancy, no documented use of antiretroviral drugs and a matched HIV sero-positive iDBS. We used 20 imputations from a uniform distribution for time from reported antenatal HIV-negative result to delivery to estimate time of HSP. Early MTCT was defined based on detection of HIV-DNA in iDBS. Estimates were adjusted for clustering, nonresponse, and weighted by SA's 2011 live-births.ResultsOf 9802 mother-infant pairs, 2738 iDBS were HIV sero-positive, including 212 HSP, resulting in a nationally weighted estimate of 3.3% HSP (95% Confidence Interval: 2.8%-3.8%). Median time of HIV-seroconversion was 32.8weeks gestation;28.3% (19.7%- 36.9%) estimated to be >36 weeks. Early MTCT was 10.7% for HSP (6.2%-16.8%) vs. 2.2% (1.7%-2.8%) for mothers with known HIV-positive status. Although they represent 2.2% of all mothers and 6.7% of HIV-infected mothers, HSP accounted for 26% of early MTCT. Multivariable analysis indicated the highest risk for HSP was among women who knew the baby's father was HIV-infected (adjusted-hazard ratio (aHR) 4.71; 1.49-14.99), or who had been screened for tuberculosis (aHR 1.82; 1.43-2.32).ConclusionsHSP risk is high and contributes significantly to early MTCT. Identification of HSP by repeat-testing at 32 weeks gestation, during labor, 6 weeks postpartum, in tuberculosis-exposed women, and in discordant couples might reduce MTCT.

Project description:BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ?500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p?=?0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ?10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p?=?0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.

Project description:BackgroundIn 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum.Methods and findingsThe Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing.ConclusionsConsidering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.

Project description:BackgroundWomen may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.Methods and findingsWe searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0-4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5-2.1) or postpartum women (HR 1.1, 95% CI 0.6-1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2-3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2-4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.ConclusionsPregnancy and the postpartum period are times of persistent HIV risk, at rates similar to "high risk" cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.

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The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV.

Publications

The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV.

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