Correction: A whole genome association study of mother-to-child transmission of HIV in Malawi
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ABSTRACT:
SUBMITTER: Joubert B
PROVIDER: S-EPMC3092107 | biostudies-literature | 2010 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundMore than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology. Thus, this study employed a genome-wide association approach to identify novel variants associated with HIV MTCT.MethodsWe conducted a nested case-control study of HIV MTCT using infants of HIV(+) mothers, drawn from a cohort study of malaria and HIV in pregnancy in Blantyre, Malawi. Whole genome scans (650,000 SNPs genotyped using Illumina genotyping assays) were obtained for each infant. Logistic regression was used to evaluate the association between each SNP and HIV MTCT.ResultsGenotype results were available for 100 HIV(+) infants (at birth, 6, or 12 weeks) and 126 HIV(-) infants (at birth, 6, and 12 weeks). We identified 9 SNPs within 6 genes with a P-value < 5 × 10(-5) associated with the risk of transmission, in either unadjusted or adjusted by maternal HIV viral load analyses. Carriers of the rs8069770 variant allele were associated with a lower risk of HIV MTCT (odds ratio = 0.27, 95% confidence interval = 0.14, 0.51), where rs8069770 is located within HS3ST3A1, a gene involved in heparan sulfate biosynthesis. Interesting associations for SNPs located within or near genes involved in pregnancy and development, innate immunological response, or HIV protein interactions were also observed.ConclusionsThis study used a genome-wide approach to identify novel variants associated with the risk of HIV MTCT in order to gain new insights into HIV MTCT etiology. Replication of this work using a larger sample size will help us to differentiate true positive findings.
| S-EPMC2873795 | biostudies-literature
Project description:BackgroundHuman promoter polymorphisms in the chemokine co-receptor 5 gene (CCR5) have been noted for association with mother-to-child transmission of HIV (HIV MTCT) as well as reduced receptor expression in vitro, but have not been clearly associated with CCR5 expression in vivo. Placental expression of CCR5 may be influenced by such polymorphisms as well as other in vivo regulatory factors.Methodology/principal findingsWe evaluated the associations between infant CCR5 polymorphisms, measures of maternal infection, and placental expression of CCR5 among mother-infant pairs in Blantyre, Malawi. RNA was extracted from placental tissue and used in multiplex real-time PCR to quantify gene expression. Through linear regression, we observed that CCR5-2554T (beta = -0.67, 95% CI = -1.23, -0.11) and -2132T (beta = -0.75, 95% CI = -0.131, -0.18) were significantly associated with reduced placental expression of CCR5. An incremental increase in CCR5 expression was observed for incremental increases in expression of two heparan sulfate genes involved in viral infection, HS3ST3A1 (beta = 0.27, 95% CI = 0.18, 0.35) and HS3ST3B1 (beta = 0.11, 95% CI = 0.06, 0.18). Among HIV infected mothers, an incremental increase in maternal HIV viral load was also associated with higher CCR5 expression (beta = 0.76, 95% CI = 0.12, 1.39). Maternal HIV status had no overall effect (beta = 0.072, 95% CI = -0.57, -0.72). Higher CCR5 expression was observed for mothers with malaria but was not statistically significant (beta = 0.37, 95% CI = -0.43, 1.18).Conclusions/significanceThese results provide in vivo evidence for genetic and environmental factors involved in the regulation of CCR5 expression in the placenta. Our findings also suggest that the measurement of placental expression of CCR5 alone is not an adequate indicator of the risk of mother-to-child transmission of HIV.
| S-EPMC2821402 | biostudies-literature
Project description:To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B').Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme.Individual-based simulation model. We simulated cohorts of 10?000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B.During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted.Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.
| S-EPMC5359470 | biostudies-literature
Project description: Not available
| S-EPMC558190 | biostudies-literature
Project description:IntroductionPregnant women living with HIV can achieve viral suppression and prevent HIV mother-to-child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi's PMTCT programme.MethodsWe conducted a two-stage cohort study among mother-infant pairs in 30 randomly selected high-volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log-binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting.ResultsOf 822 mother-infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81).ConclusionsMTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.
| S-EPMC7982503 | biostudies-literature
Project description:BackgroundThe mechanism of mother-to-child transmission (MTCT) of HIV-1 is not well described.MethodsOf 328 HIV-infected mother-infant pairs, we identified 91 that had discordant angiotensin I-converting enzyme and glutathione S-transferase M1 alleles. Maternal alleles in cord blood were quantified with real-time polymerase chain reaction, as indicators of microtransfusions.ResultsHIV-1 infected infants had more maternal DNA in cord blood than their uninfected counterparts. Increased maternal DNA in cord blood was associated with preterm delivery, low birth weight, and maternal immunosuppression.ConclusionIntrapartum MTCT was associated with placental microtransfusions. The associations among placental microtransfusion, in-utero MTCT, maternal immunosuppression, and poor birth outcome should be further investigated.
| S-EPMC2443405 | biostudies-literature
Project description: Not available
| S-EPMC1513047 | biostudies-literature
Project description:BackgroundMale Involvement (MI) in the Prevention of Mother to Child Transmission (PMTCT) of Human Immunodeficiency Virus (HIV) services is essential in a patriarchal society where men are decision makers of the household. Male partners have a role in the woman's risk of acquiring HIV, uptake of HIV testing and participation in Mother to Child Transmission (MTCT) prevention programmes. Although MI is important for uptake of PMTCT interventions, it remains low in Africa. The purpose of this study was to identify factors that promote and hinder MI in PMTCT services in antenatal care (ANC) services in Blantyre, Malawi. Understanding of the factors that influence MI will assist in developing strategies that will involve men more in the programme thereby improving the uptake of PMTCT and HIV testing and counselling services by women and men respectively.MethodsAn exploratory qualitative study was conducted from December 2012 to January 2013 at South Lunzu Health Centre (SLHC) in Blantyre, Malawi. It consisted of six face to face Key Informant Interviews (KIIs) with health care workers and four Focus Group discussions (FGDs) with 18 men and 17 pregnant women attending antenatal care at the clinic. The FGDs were divided according to sex and age. All FGDs and KIIs were digitally recorded and simultaneously transcribed and translated verbatim into English. Data were analysed using thematic content analysis.ResultsParticipants in both FGDs and KIIs identified the following barriers: lack of knowledge of MI in PMTCT, socioeconomic factors, relationship issues, timidity to be seen in a woman's domain, unplanned and or extramarital pregnancies, fear of knowing one's HIV status, unwillingness to be associated with the service, health facility based factors, peer influence and cultural factors. The factors that would potentially promote male involvement were categorized into community, health facility and personal or family level factors.ConclusionsThe factors that may hinder or promote MI arise from different sources. The success of MI lies on recognizing sources of barriers and averting them. Factors that promote MI need to be implemented at different levels of health care.
| S-EPMC4226974 | biostudies-literature
Project description:BackgroundMale involvement (MI) in Prevention of mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) services remains low despite the progress registered in the implementation of the PMTCT program. Male involvement in PMTCT is a fairly new concept in Malawi that has not been fully implemented within PMTCT service provision despite its inclusion in the PMTCT guidelines. One of the reasons for the limited MI is the lack of knowledge on both its relevance and the role of men in the program. Currently, men have been encouraged to participate in PMTCT services without prior research on their understanding of the relevance and their role in PMTCT. This information is vital to the development of programs that will require MI in PMTCT. The objective of this study was to explore the views of men, pregnant women and health care providers on the importance and roles of MI in PMTCT services in Blantyre Malawi.MethodsAn exploratory descriptive qualitative study was conducted from December 2012 to January 2013 at South Lunzu Health Centre (SLHC) and its catchment area in Blantyre, Malawi. We conducted 6 key informant interviews (KIIs) with health care workers and 4 focus group discussions (FGDs) with 18 men and 17 pregnant women. Interviews and discussions were digitally recorded and simultaneously transcribed and translated into English. Data were analyzed using framework analysis approach.ResultsThe major themes that emerged on the relevance of MI in PMTCT were a) uptake of interventions along the PMTCT cascade b) support mechanism and c) education strategy. Lack of MI in PMTCT was reported to result into non-disclosure of HIV test results and non-compliance with PMTCT interventions.ConclusionsMale involvement is paramount for the uptake of interventions at the different cascades of PMTCT. The absence of male involvement may compromise compliance with PMTCT interventions.
| S-EPMC4422229 | biostudies-literature
Project description:This study examined HIV superinfection in HIV-infected women postpartum, and its association with mother-to-child transmission (MTCT).Plasma samples were obtained from HIV-infected women who transmitted HIV to their infants after 6 weeks of age (transmitters, n?=?91) and HIV-infected women who did not transmit HIV to their infants (nontransmitters, n?=?91). These women were originally enrolled in a randomized trial for prevention of MTCT of HIV in Malawi (Post-Exposure Prophylaxis of Infants trial in Malawi).Two HIV genomic regions (p24 and gp41) were analyzed by next-generation sequencing for HIV superinfection. HIV superinfection was established if the follow-up sample contained a new, phylogenetically distinct viral population. HIV superinfection and transmission risk were examined by multiple logistic regression, adjusted for Post-Exposure Prophylaxis of Infants study arm, baseline viral load, baseline CD4 cell count, time to resumption of sex, and breastfeeding duration.Transmitters had lower baseline CD4 cell counts (P?=?0.001) and higher viral loads (P?<?0.0001) compared with nontransmitters. There were five cases of superinfection among transmitters (rate of superinfection?=?4.7/100 person-years) compared with five cases among the nontransmitters (rate of superinfection?=?4.4/100 person-years; P?=?0.78). HIV superinfection was not associated with increased risk of postnatal MTCT of HIV after controlling for maternal age, baseline viral load, and CD4 cell count (adjusted odds ratio?=?2.32, P?=?0.30). Longer breastfeeding duration was independently associated with a lower risk of HIV superinfection after controlling for study arm and baseline viral load (P?=?0.05).There was a significant level of HIV superinfection in women postpartum, but this was not associated with an increased risk of MTCT via breastfeeding.
| S-EPMC4609898 | biostudies-literature