Perinatal Mother-to-child Transmission Research Articles

Mycoplasma genitalium infection among HIV-infected pregnant African women and implications for mother-to-child transmission of HIV.

Many sexually transmitted infections increase risk of mother-to-child transmission (MTCT) of HIV, but the effect of Mycoplasma genitalium is not known. We hypothesized that M. genitalium infection would be common among HIV-infected pregnant women and could be associated with in-utero and intrapartum MTCT. Observational case-cohort study. The current study used specimens from a Kenyan perinatal MTCT cohort (1999-2005) involving HIV-infected women and their infants, who received short-course zidovudine for prevention of MTCT. Vaginal swabs collected at 32 weeks gestation were tested for M. genitalium using a transcription-mediated amplification assay. Infant perinatal HIV infection was determined at birth and 4 weeks of age by DNA PCR. Using a case-cohort design, a random sample was generated with 3 : 1 control : case ratio; prevalence and correlates of M. genitalium were assessed with chi-squared and t tests; predictors of infant outcomes were analyzed using logistic regression. Among 220 HIV-infected pregnant women evaluated, 47 women (21.4%) had M. genitalium. Antenatal M. genitalium infection was associated with higher HIV RNA in plasma (5.0 vs. 4.6 log10 copies/ml in M. genitalium-positive vs. M. genitalium-negative women, P = 0.02) at 32 weeks. Women with M. genitalium were less likely to report prior sexually transmitted infections and genital ulcers (both P = 0.05). There was no association found between exposure to M. genitalium and perinatal MTCT (odds ratio = 0.72, 95% confidence interval 0.35, 1.51, P = 0.39). Vaginal M. genitalium infection was frequently detected among Kenyan HIV-infected pregnant women and was associated with higher plasma HIV levels, but was not associated with perinatal transmission of HIV.

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

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. 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. 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/μL) 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. 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.

Mother-to-child transmission of HIV in Australia and other high-income countries: Trends in perinatal exposure, demography and uptake of prevention strategies.

Virtual elimination of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is a global target. A review of the literature was conducted using medical databases and health department websites to examine the current trends related to perinatal HIV exposure and MTCT in Australia in comparison with other high-income countries (HICs). The review discusses the uptake of prevention strategies and barriers that impede MTCT prevention. The literature suggests an increase in the numbers of HIV-exposed deliveries, but a marked decline in the rates of MTCT within HICs. MTCT remains high when the mother's HIV infection is diagnosed late or postpartum. Data supports increasing trends of perinatal HIV exposure in migrant populations from low- and middle-income countries (particularly African women). Increased uptake and earlier initiation of antiretroviral therapy (ART) was associated with overall MTCT decline. Caesarean section remains the main mode of delivery described; however, the numbers of planned vaginal deliveries are increasing over time. Heterogeneity of data periods and outcome measures within published literature made comparisons between countries difficult. Future development should focus on clear national guidelines and a potential national database for perinatal HIV, culturally appropriate service provision, and more evidence on acute infections in pregnancy and the effects that longer duration and increased uptake of ART has on the fetus and resistance to ART.

The spectrum of HIV mother-to-child transmission risk.

IntroductionWith the implementation of combined antiretroviral therapy (cART) and prevention of mother-to-child transmission (MTCT) we observed dramatic decreases in rates of perinatal MTCT of HIV, 0.3% in France in women with plasma viral load (pVL) <50 c/mL at delivery. We describe a case of MTCT which occurred despite virologic suppression of the mother at delivery, the first case in our centre since 2002.Description of the caseA 26-year-old black woman, Guinea-native, living in France since 2007, was diagnosed with HIV-1 CRF02 in 2008 and lost to follow-up since November 2012 after second delivery (2 female born in March 2009 and October 2012, uninfected). Third pregnancy began in July 2013 and baseline characteristics in September were as follows: week 13 of gestational age (GA), CDC stage A, CD4 317/mm3, pVL 4.89 log c/mL. cART with abacavir/lamivudine and atazanavir/ritonavir 300/100 mg daily (qd) was introduced. VL decreased to 2.4 log c/mL in 4 weeks and CD4 increased to 456/mm3. In December, at week 22 of GA, viral rebound at 4.14 log c/mL due to sub-optimal maternal adherence was observed. After counselling, pVL decreased to 1.69 log c/mL in March 2014, at week 35 of GA and 1.3 log c/mL at delivery. As pVL was <400 c/mL at week 36 of GA, vaginal delivery with IV zidovudine was decided. However, because of poor/uncertain maternal adherence to cART, the neonate was treated with a combination of 2 drugs (lamivudine-nevirapine) with the 4-week zidovudine regimen, until the result of delivery pVL. This combination was stopped at day 2 when maternal delivery pVL (22 c/mL) was received and standard oral zidovudine prophylaxis was continued. Infant was tested for HIV infection at baseline (day 3) and found to be HIV-infected (HIV-RNA 60 c/mL) attesting in-utero HIV transmission. On day 15, zidovudine prophylaxis was discontinued and treatment for HIV infection initiated with standard cART according to the French Paediatric Antiretroviral Guidelines.ConclusionsThe risk of HIV acquisition is low in infants born to women who receive standard cART during pregnancy and labour and achieve undetectable VL at delivery. However, transmission remains a hazard, with possibility of in-utero infection during episodes of non-adherence, and the risk of a possible MTCT has to be mentioned to all pregnant women.

Persistently high perinatal transmission of HIV: assessment of risk factors.

Despite dramatic decreases in rates of perinatal mother-to-child-transmission (PMTCT) of HIV in the United States, rates in some groups remain above the national average. Our objective was to examine factors contributing to a high rate of PMTCT of HIV. We conducted a retrospective chart review of HIV-exposed infants and their mothers referred to the University of Texas-Houston Pediatric HIV Clinic from January 2000 to June 2007. Of 367 newborns studied, 22 (6%) acquired HIV infection perinatally. Associated risk factors included inadequate prenatal care, failure to receive antiretroviral therapy during pregnancy, detectable viral load and intravenous drug abuse. The composite rate of PMTCT in this high risk cohort was at least 3-fold higher than expected from the current standard of care. Reduction of rates of PMTCT in our population will require ensuring access to appropriate prenatal care, including delivery of antiretroviral therapy and addressing issues of illicit drug use.

Altered Vaginal Microbiota Are Associated With Perinatal Mother-to-Child Transmission of HIV in African Women From Burkina Faso

Mother-to-child transmission (MTCT) of HIV remains a significant problem in resource-limited settings, despite the advent of antiretroviral therapies. Because perturbations in vaginal microbial communities are associated with sexual transmission of HIV, we determined whether perinatal MTCT is associated with the vaginal microbiotas of HIV-infected mothers. We conducted a retrospective analysis of cervicovaginal microbiotas by pyrosequencing of bacterial 16S rRNA genes (median 350 sequences per sample) from 10 transmitters and 54 nontransmitters during a perinatal MTCT prevention clinical trial of azidothymidine and the microbicide benzalkonium chloride. Logistic regression was performed adjusting for multiple covariates, including CD4(+) T-cell numbers and treatment group, to correlate abundances of microbial taxa with perinatal MTCT. The vaginal microbiotas of these subjects were dominated by several lactobacilli species, although a subset of subjects was colonized by diverse anaerobic species. MTCT of HIV was associated with significantly greater relative abundances of several groups of microorganisms. Most notably, among the abundant bacterial species, Gardnerella vaginalis was significantly enriched in cases of antepartum transmission, compared with nontransmission (odds ratio 1.7; P = 0.004). Neither azidothymidine nor benzalkonium chloride treatment was associated with shifts in microbial distributions compared with the placebo control group. These data suggest that alterations in vaginal microbial communities are associated with an increased risk for perinatal MTCT, consistent with results with horizontal transmission of HIV. Therefore, determining the mucosal features associated with alterations in vaginal microbial communities may guide efforts to modulate the risk for HIV MTCT.

Antenatal prevention of mother to child transmission of HIV

AbstractAn effective perinatal mother to child transmission (PMTCT) programme will reduce perinatal acquired HIV infections. This goal is within reach of the South African public health sector. Early antenatal attendance and knowledge of HIV status allows sufficient time to implement highly active antiretroviral therapy (HAART) or ART intervention. Both measures have been proved to be efficient to reduce MTCT of HIV. A transmission rate of 2% can be achieved with a dual therapy regimen in non-breastfeeding women. Mono therapy with single dose nevirapine (sd NVP) often fails due to the once off nature of the intervention as opposed to ample opportunity to administer zudovudine (AZT) antenatally with dual therapy. A higher CD4 threshold to initiate HAART increases the window of opportunity while women are reasonably healthy. Irrespective of the maternal disease the newborn babies receive the same ART regimen. Women requiring HAART following pregnancy with an interval of 6 months or longer since NVP exposure...

HIVNET 024: Placental histology and mother to child transmission (MTCT) of HIV

(MTCT) OF HIV ROBERT GOLDENBERG, VICTOR MUDENDA, TAHA TAHA, IRVING HOFFMAN, WAFAIE FAWZI, ELIZABETH BROWN, University of Alabama at Birmingham, Obstetrics/Gynecology, Birmingham, Alabama, University Teaching Hospital, Pathology, Lusaka, Zambia, Johns Hopkins University, Baltimore, Maryland, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Harvard University, Boston, Massachusetts, Fred Hutchinson Cancer Research Center, Seattle, Washington OBJECTIVE: Studies performed prior to the use of antivirals have shown a relationship between histologic chorioamnionitis, (neutrophilic infiltrates in the chorioamnion) and MTCT of HIV. A recent publication describing nevirapine-treated women suggests MTCT of HIV is related to mononuclear, but not neutrophilic infiltration. STUDY DESIGN: During a trial of the use of antibiotics to reduce MTCT of HIV in 2098 HIV-infected nevirapine-treated women, we evaluated the relationship between neutrophilic and mononuclear infiltration of the decidual basalis, the chorioamnion and the umbilical cord, and MTCT of HIV. Marked infiltration was compared to none/slight. A single pathologist who had no clinical information at the time of the evaluation performed the histologic evaluation. Infant HIV infection was determined by PCR at birth and at 6 weeks. RESULTS: The rate of MTCT of HIV at birth was 7.3%, between birth and 4-6 weeks 7.5%, and total perinatal MTCT, 15.2%. (In the pre-nevirapine studies, the total MTCT rate was 25-30%.) Marked neutrophilic and mononuclear infiltration into the membranes (29% and 35%) and decidua (19% and 44%) were common in HIV-infected women. Neither marked neutrophilic nor mononuclear infiltration at any site was associated with infant HIV status at birth, with developing an HIV infection between birth and 6 weeks, or with infant HIV status at 6 weeks. For example, marked neutrophilic membrane infiltration vs none/slight was not associated with infant HIV status at birth (8.7 vs 7.3%, p=NS), the development of HIV between birth and 6 weeks (7.8 vs 6.7%, p=NS) or with HIV status at 6 weeks (15.3 vs 14.5%, p=NS). CONCLUSION: Despite previous reports of an association between chorioamnionitis and MTCT of HIV, this large study demonstrated no association between either neutrophilic or mononuclear inflammation at any site and MTCT of HIV. We hypothesize that the use of nevirapine in this, as opposed to many earlier studies, reduced the portion of MTCT of HIV associated with chorioamnionitis.

Mother-to-child HIV transmission in resource poor settings: how to improve coverage?

To review coverage of the current nevirapine prevention model in Coast Provincial General Hospital (CPGH) in Mombasa, Kenya, and to reflect on alternative models to reduce mother-to-child transmission (MTCT) of HIV. At the antenatal clinic, health information is provided, followed by pre-test HIV voluntary counselling and testing (VCT). Because many women deliver at home, HIV-infected women are provided with a tablet of 200 mg nevirapine for themselves, and with 0.6 ml (6 mg) nevirapine in a luer lock syringe for the baby. Data on coverage are provided from antenatal records and delivery registers. Out of 3564 first-visit pregnant women receiving health education, 2516 were counselled (71%) and 2483 were tested (97%); 348 were HIV positive (14%), and 106 women took nevirapine in labour, resulting in an overall coverage rate of 20%. In the same period, approximately 6000 women gave birth in CPGH, of whom 21% had attended a facility with VCT services. Assuming an overall HIV prevalence of 14%, 840 mother-infant pairs could have received a preventative intervention with a hospital policy of antepartum as well as intrapartum testing and treatment in place. The coverage of perinatal MTCT was low as a result of a variety of programme elements requiring urgent improvement at different levels. Alternative models, including intrapartum testing, should be considered as a safety net for women without access to VCT before delivery, and recommendations for nevirapine should be considered in the light of home deliveries.

Placental Inflammation and Perinatal Transmission of HIV-1

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa. Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p = .025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

Placental inflammation and perinatal transmission of HIV-1.

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.