Protective Role of BST2 Polymorphisms in Mother-to-Child Transmission of HIV-1 and Adult AIDS Progression.
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SUBMITTER: Kamada AJ
PROVIDER: S-EPMC4911235 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
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Protective Role of BST2 Polymorphisms in Mother-to-Child Transmission of HIV-1 and Adult AIDS Progression.
Kamada Anselmo J AJ Bianco Anna M AM Zupin Luisa L Girardelli Martina M Matte Maria C C MC Medeiros Rúbia Marília de RM Almeida Sabrina Esteves de Matos SE Rocha Marineide M MM Segat Ludovica L Chies José A B JA Kuhn Louise L Crovella Sergio S
Journal of acquired immune deficiency syndromes (1999) 20160701 3
Bone marrow stromal cell antigen-2 (BST-2)/Tetherin is a restriction factor that prevents Human immunodeficiency virus type 1 (HIV-1) release from infected cells and mediates pro-inflammatory cytokine production. This study investigated the risk conferred by single nucleotide polymorphisms (rs919266, rs9192677, and rs9576) at BST-2 coding gene (BST2) in HIV-1 mother-to-child transmission and in disease progression. Initially, 101 HIV-1+ pregnant women and 331 neonates exposed to HIV-1 from Zambi ...[more]
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Project description:Introduction: Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infection and HIV-1 mother-to-child transmission (MTCT) in different populations. We investigated the role of DEFB1 gene (encoding for hBD-1) functional polymorphisms in the susceptibility to HIV-1 MTCT in a population from Zambia. Methods: Four selected polymorphisms within DEFB1 gene, three at the 5' untranslated region (UTR), namely -52G?>?A (rs1799946), -44C?>?G (rs1800972) and -20G?>?A (rs11362) and one in the 3'UTR, c.*87A?>?G (rs1800972), were genotyped in 101 HIV-1 positive mothers (26 transmitters -27% and 75 not transmitters -73%) and 331 infants born to HIV-1 infected mothers (85 HIV-1 positive -26% and 246 exposed but not infected -74%). Results: DEFB1 c.*87-A allele was more frequent among HIV- children with respect to HIV+ (with intrauterine MTCT). Concerning DEFB1 haplotypes, GCGA haplotype resulted more represented in HIV- than HIV+ infants and DEFB1 ACGG haplotype presented increased frequency in HIV- children respect to HIV+ (with intra-partum MTCT) (p?=?.02, p?=?.002 and p?=?.006, respectively). Conclusions: DEFB1 polymorphisms were significantly associated with decreased risk of HIV-1 infection acquisition in the studied Zambian population suggesting that they may play a role in HIV-1 MTCT.
| S-EPMC6202264 | biostudies-literature
Project description:Background:Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is decreasing worldwide; however, achieving the MTCT elimination target of 2% by 2020 and 0% by 2030 is challenging in resource-limited countries. The purpose of this study is to determine the evolution of the HIV transmission rate in infants from 2007 to 2018 and to identify the risk factors of HIV transmission among HIV-exposed infants in Vietnam. Patients and Methods:A prospective cohort study of 608 HIV-exposed infants was conducted at the Pediatric Outpatient Clinic (pOPC) of the Women and Children Hospital of An Giang, Vietnam between September 2007 and December 2019. A follow-up registration book was used to collect data, which were entered into Microsoft Excel and analyzed by SPSS version 22.0. Both bivariate and multivariate analyses were carried out to identify associations. Results:A total of 608 HIV-exposed infant were enrolled in the study, of which 472 were included in the final analysis. The median age of infants at enrollment to follow-up was 6.3 weeks (interquartile range [IQR]=6.0-6.9 weeks). A total of 42 infants out of 472 were infected with HIV, giving an overall MTCT rate of 8.9% (95% confidence interval (CI)=6.4-12.0). The transmission rate decreased from 27.9% in 2007 to 0% in 2018. Absence of maternal ARV (antiretrovirals) intervention before or during pregnancy (AOR=40.6, 95% CI=5.5-308) and absence of ARV prophylaxis for HIV-exposed infants (AOR=3.4, 95% CI=1.1-10.3) were significantly and independently associated with MTCT of HIV in this study. Conclusion:There is a significant progress on the reduction of MTCT rate in An Giang, Vietnam. Absence of ART interventions for mothers and infants are significant factors associated with HIV transmission. Providing free ARV and increasing the coverage of ARV intervention for pregnant women are keys for reducing the MTCT rate in the future.
| S-EPMC7371555 | biostudies-literature
Project description: Not available
| S-EPMC1513047 | 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
Project description:BackgroundStrategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section delivery, and avoiding giving children chewed food. In some settings, these interventions may not be practical, feasible, or affordable. Simple, inexpensive, and effective interventions (that could potentially be implemented even in the absence of prenatal HIV testing programmes) would be valuable. Vitamin A, which plays a role in immune function, is one low-cost intervention that has been suggested in such settings.ObjectivesTo summarize the effects of giving vitamin A supplements to HIV-positive women during pregnancy and after delivery.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 25 August 2017, and checked the reference lists of relevant articles for eligible studies.Selection criteriaWe included randomized controlled trials conducted in any setting that compared vitamin A supplements to placebo or no intervention among HIV-positive women during pregnancy or after delivery, or both.Data collection and analysisAt least two review authors independently assessed study eligibility and extracted data. We expressed study results as risk ratios (RR) or mean differences (MD) as appropriate, with their 95% confidence intervals (CI), and conducted random-effects meta-analyses. This is an update of a review last published in 2011.Main resultsFive trials met the inclusion criteria. These were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005 and none of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses (daily during pregnancy; a single dose immediately after delivery, or daily doses during pregnancy plus a single dose after delivery). Women allocated to comparison arms received identical placebo (6601 women, 4 trials) or no intervention (697 women, 1 trial). Four trials (with 6995 women) had low risk of bias and one trial (with 303 women) had high risk of attrition bias.The trials show that giving vitamin A supplements to HIV-positive women during pregnancy, the immediate postpartum period, or both, probably has little or no effect on mother-to-child transmission of HIV (RR 1.07, 95% CI 0.91 to 1.26; 4428 women, 5 trials, moderate certainty evidence) and may have little or no effect on child death by two years of age (RR 1.06, 95% CI 0.92 to 1.22; 3883 women, 3 trials, low certainty evidence). However, giving vitamin A supplements during pregnancy may increase the mean birthweight (MD 34.12 g, 95% CI -12.79 to 81.02; 2181 women, 3 trials, low certainty evidence) and probably reduces the incidence of low birthweight (RR 0.78, 95% CI 0.63 to 0.97; 1819 women, 3 trials, moderate certainty evidence); but we do not know whether vitamin A supplements affect the risk of preterm delivery (1577 women, 2 trials), stillbirth (2335 women, 3 trials), or maternal death (1267 women, 2 trials).Authors' conclusionsAntepartum or postpartum vitamin A supplementation, or both, probably has little or no effect on mother-to-child transmission of HIV in women living with HIV infection and not on antiretroviral drugs. The intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission.
| S-EPMC5618453 | biostudies-literature
Project description:BackgroundThe reproductive health and Prevention of Mother-to-Child Transmission (PMTCT) of HIV programs in Iran were integrated as a pilot project in September 2014. This study aims to provide a comprehensive evaluation and analysis of the PMTCT of HIV program in Iran.MethodsThe pilot phase of PMTCT of HIV was launched in early September 2014 in selected centers including 170 health centers and 40 hospitals affiliated to medical universities of 16 provinces of Iran. In each medical university, a researcher-made checklist was administered to all newly-diagnosed HIV-positive pregnant women by an AIDS expert. Data was analyzed using SPSS 19.ResultsOverall, 69.4% of eligible pregnant women were enrolled in the pilot phase. From 134 reactive cases, 76 (56.7%) were confirmed as HIV positive. ARV consumption was irregular in 10 (13.2%) of HIV positive pregnant women. Also, 82.5% had CD4 count more than 350 after treatment, with an average of 55.5% increase in the number of CD4 in comparison to the baseline, and 84.8% had viral load suppression (< 200 copies/ml). Counseling and testing was done for the husbands of 75% of the women that resulted in the identification of 15 (39.5%) new HIV cases among husbands. Among the tested individuals, 23 (60.5%) males already knew their HIV status and were registered as HIV patients. HIV was diagnosed in one (1.5%) newborn.ConclusionImplementation of rapid HIV testing and PMTCT in Iran is one of the strengths of the national HIV control program. To eliminate MTCT, it is necessary to understand and overcome the barriers and challenges to the program in the pilot phase.
| S-EPMC7948351 | biostudies-literature
Project description:The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P?=?0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P?=?0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.
| S-EPMC3714266 | biostudies-literature
Project description:ImportanceFrom 2004 to 2014, the US President's Emergency Plan for AIDS Relief (PEPFAR) invested more than $248 000 000 in the prevention of mother-to-child transmission (PMTCT) of HIV in Kenya. Concurrently, child mortality in Kenya decreased by half.ObjectiveTo identify the extent to which the decrease in child mortality in Kenya is associated with PEPFAR funding for PMTCT of HIV.Design, setting, and participantsThis population-based survey study conducted in Kenya estimated the association between annual per capita PEPFAR funding for PMTCT (annual PCF) and cumulative per capita PEPFAR funding for PMTCT (cumulative PCF), extracted using 2004-2014 country operational reports as well as individual-level health outcomes, extracted from the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys and the 2007 and 2012 Kenya AIDS Indicator Surveys. The study included children of female respondents to the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys who were born 1 to 60 months (for neonatal mortality) or 12 to 60 months (for infant mortality) before the survey, as well as female respondents who had recently given birth and reported on HIV testing during antenatal care (ANC) during the 2007-2014 surveys. Results were adjusted for year, province, and survey respondent characteristics. Statistical analysis was performed from July 8, 2016, to December 10, 2018.Main outcomes and measuresNeonatal mortality was defined as death within the first month of life and infant mortality was defined as death within the first year of life. HIV testing during ANC was defined as receiving counseling on PMTCT, undergoing an HIV test, and receiving test results during ANC.ResultsThe analysis included 33 181 neonates (16 870 boys), 26 876 infants (13 679 boys), and 20 775 mothers (mean [SD] age, 28.0 [6.7] years). PEPFAR funding was not associated with neonatal mortality. A $0.33 increase in annual PCF, corresponding to the difference between the 75th and 25th (interquartile range) percentiles of funding, was significantly associated with a 16% (95% CI, 4%-27%) reduction in infant mortality after a 1-year lag. A 14% to 16% reduction persisted after 2- and 3-year lags, and comparable reductions were observed for unlagged and 1-year lagged cumulative PCF. An increase of 1 interquartile range in cumulative PCF was associated with a 7% (95% CI, 3%-11%) increase in HIV testing during ANC, which intensified with subsequent lags. Between 2004 and 2014, sustained funding levels of $0.33 annual PCF could have averted 118 039 to 273 924 infant deaths.Conclusions and relevanceEvidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation.
| S-EPMC6745052 | biostudies-literature
Project description:Exposure of the infant's gut to cell-associated and cell-free HIV-1 trafficking in breast milk (BM) remains a primary cause of mother-to-child transmission (MTCT). The mammary gland represents a unique environment for HIV-1 replication and host-virus interplay. We aimed to explore the origin of the virus transmitted during breastfeeding, and the link with quasi-species found in acellular and cellular fractions of breast-milk (BM) and in maternal plasma. The C2-V5 region of the env gene was amplified, cloned and sequenced from the RNA and DNA of BM, the RNA from the mother's plasma (PLA) and the DNA from infant's dried blood spot (DBS) in 11 post-natal mother-infant pairs. Sequences were assembled in Geneious, aligned in ClustalX, manually edited in SeAL and phylogenetic reconstruction was undertaken in PhyML and MrBayes. We estimated the timing of transmission (ETT) and reconstructed the time for the most recent common ancestor (TMRCA) of the infant in BEAST. Transmission of single quasi-species was observed in 9 of 11 cases. Phylogenetic analysis illustrated a BM transmission event by cell-free virus in 4 cases, and by cell-associated virus in 2 cases but could not be identified in the remaining 5 cases. Molecular clock estimates, of the infant ETT and TMRCA, corresponded well with the timing of transmission estimated by sequential infant DNA PCR in 10 of 11 children. The TMRCA of BM variants were estimated to emerge during gestation in 8 cases. We hypothesize that in the remaining cases, the breast was seeded with a long-lived lineage latently infecting resting T-cells. Our analysis illustrated the role of DNA and RNA virus in MTCT. We postulate that DNA archived viruses stem from latently infected quiescent T-cells within breast tissue and MTCT can be expected to continue, albeit at low levels, should interventions not effectively target these cells.
| S-EPMC4368793 | biostudies-literature
Project description:Mother-to-child HIV-1 transmission pairs represent a good opportunity to study the dynamics of CTL escape and reversion after transmission in the light of shared and non-shared HLA-alleles. Mothers share half of their HLA alleles with their children, while the other half is inherited from the father and is generally discordant between mother and child. This implies that HIV-1 transmitted from mother to child enters a host environment to which it has already partially adapted. Here, we studied viral evolution and the dynamics of CTL escape mutations and reversion of these mutations after transmission in the context of shared and non-shared HLA alleles in viral variants obtained from five mother-to-child transmission pairs. Only limited HIV-1 evolution was observed in the children after mother-to-child transmission. Viral evolution was mainly driven by forward mutations located inside CTL epitopes restricted by HLA alleles inherited from the father, which may be indicative of CTL pressure.
| S-EPMC5381489 | biostudies-literature