Mother-to-child Transmission Of HIV Research Articles

Contraception choices in a cohort of HIV+ women in the era of highly active antiretroviral therapy

Background The study was conducted to determine whether increased desire for fertility coupled with increased awareness of reduction in mother-to-child HIV transmission (MTCT) with increased availability and use of highly active antiretroviral therapy (HAART) has been associated with reduction in use of tubal sterilization as a form of contraception among women infected with HIV. Study Design One hundred HIV+ women, 18 to 45 years of age, receiving care at university-affiliated HIV facilities between October 2008 and February 2009, were surveyed about their contraceptive knowledge and practices. We performed descriptive analysis of population characteristics to determine contraception choices and fertility desires following initiation of HAART. Results The study group was composed of women with median age of 35 years, 55% African American, 18% Caucasians, 19% Hispanic and 8% “other”. Most (63%) were single; 36% were married. Contraception choices were condom 61%, injectable contraceptive 7%, pills 6% and only 3% said they used female sterilization. Thirty-four percent of respondents said that their choice of contraception was based primarily on ease of use, 19% said that their choice was primarily based on convenience and only 9% said that their choice was primarily based on provider recommendation. Desire for future childbearing increased to 19% following knowledge that MTCT can be reduced by taking antiretroviral therapy (ARV) and to 22% following initiation of ARV. Conclusions Initiation of ARV and awareness that maternal treatment can reduce MTCT may explain lower use of female sterilization as a form of contraception among a cohort of HIV+ women in the post HAART era.

Dynamic Characteristic Analysis of HIV Mother to Child Transmission in China

To explore dynamic characteristics of the HIV mother to child transmission (MTCT) epidemic in China. A deterministic dynamic transmission model was used to determine the effect of key parameters on the likely long-term trends of the HIV MTCT epidemic in China. Matlab 7.0 was used to develop the model. The number of the susceptibles (S), the transmission rate (β), and the screening proportion (α) of HIV positive pregnant women have the greatest impact on the HIV MTCT epidemic in China. The growth of the MTCT epidemic in China could not be controlled only by decreasing the MTCT transmission rate. The prevalence of HIV positive women should be reduced and more pregnant women should be tested for HIV. Prevention of MTCT (PMTCT) should focus not only on the reduction of HIV transmission rates and incidences of HIV among women but also on the increase of HIV testing for pregnant women. The most cost-effective PMTCT means for China should be investigated in future studies.

Mother-to-Child Transmission (MTCT) of HIV and Drugs of Abuse in Post-Highly Active Antiretroviral Therapy (HAART) Era

In the pre-highly active antiretroviral therapy (HAART) era, prenatal "vertical" mother-to-child transmission (MTCT) of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant contributory factor of MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. But, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT is of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms that are addressed in detail including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load though a variety of putative mechanisms such as: (a) promoting HIV replication in monocyte/macrophages; (b) increasing the expression of CCR5 receptors; (c) decreasing the expression of CCR5 receptor ligands; (d) increasing the expression of CXCR4 receptors; (e) increasing the expression of DC-SIGN; (f) impairing the efficacy of HAART through drug-drug interaction; and (g) promoting HIV mutation and replication through non-adherence to HAART.

Pregnancy in HIV-infected teenagers in London

The aim of the study was to describe pregnancies in HIV-infected teenagers. A review of the case notes of HIV-infected pregnant teenagers aged 13-19 years from 12 London hospitals was carried out for the period 2000-2007. There were 67 pregnancies in 58 young women, of whom one was known to have acquired HIV vertically. The overall mother-to-child transmission (MTCT) rate of HIV was 1.5% (one of 66). There were 66 live births. Median ages at HIV diagnosis and conception were 17 and 18 years, respectively. Sixty-three per cent of women were diagnosed with HIV infection through routine antenatal screening. Eighty-two per cent of pregnancies (41 of 50) were unplanned, with 65% of women (26 of 40) using no contraception. Forty-three per cent of the women (20 of 46) had a past history of a sexually transmitted infection (STI). In 63 pregnancies, antiretroviral therapy was started post-conception, with prevention of HIV MTCT the only indication in 81% of cases. Fifty-eight per cent of those on highly active antiretroviral therapy (HAART) had an undetectable HIV viral load by delivery. Eighty-seven per cent were uncomplicated pregnancies. Seventy-one per cent delivered by Caesarean section and 21% (14 of 64) had a preterm delivery (<37 weeks). In the 12 months after delivery, 45% of women received contraceptive advice and 25% of women became pregnant again. Obstetric and virological outcomes were favourable in this group of HIV-infected young women. However, the majority of pregnancies were unplanned with poor documentation of contraception use and advice and low rates of STI screening. A quarter of women conceived again within 12 months of delivery. Effective measures to reduce STIs, unplanned pregnancies and onward HIV transmission in HIV-infected teenagers are needed.

Indirect timing estimation of Mother to Child HIV transmission (MTCT)

Indirect timing estimation of Mother to Child HIV transmission (MTCT)

Maternal-Fetal Pharmacokinetics and Dynamics of a Single Intrapartum Dose of Maraviroc in Rhesus Macaques

Single-dose nevirapine (NVP) is effective in reducing mother-to-child transmission (MTCT) of HIV; however, the subsequent development of drug resistance is problematic. The pharmacokinetic profile of the HIV entry inhibitor maraviroc after a single intrapartum dose in rhesus macaques was studied to determine whether maraviroc could serve as an alternative to NVP in a single-dose strategy. Four pregnant macaques received an oral dose of maraviroc 2 h before delivery, and both infant and maternal plasma maraviroc concentrations and CCR5 receptor occupancy on CD4(+) lymphocytes were measured over time. Maximum plasma maraviroc concentrations were found at delivery (2-h-postintrapartum dose) in both the mothers and infants, with median concentrations of 974 ng/ml (range, 86 to 2,830 ng/ml) and 22 ng/ml (range, 4 to 99 ng/ml), respectively. Maraviroc was detected in the plasma of mothers up to 48 h after dosing but only as long as 3.5 h in the infants. The median fetal-maternal area under the concentration-time curve (AUC) ratio was 0.009 (range, 0.000 to 0.015). Maraviroc receptor occupancy data showed evidence of unprotected CCR5 receptors on CD4(+) cells in the mothers 24 to 48 h after dosing. Extremely low CCR5 expression on CD4(+) cells of newborn macaques prevented determination of receptor occupancy in the infants. In rhesus macaques, maraviroc was poorly transferred across the placenta and was quickly cleared from the infants' blood. The low concentrations of fetal maraviroc and short pharmacokinetic profile in infants suggest that a single maternal intrapartum dose of maraviroc would not be effective in reducing the risk of MTCT of HIV.

Bloody Traditional Procedures Performed During Infancy in the Oropharyngeal Area Among HIV+ Children: Implication from the Perspective of Mother-to-Child Transmission of HIV

Although bloody traditional procedures are very common in Ethiopia, this is the first report on infants. None of the literature attributed such practices as risk factor for mother-to-child transmission (MTCT) of HIV. Analysis was done to 1,163 children and found that 552 (47.5%) bloody traditional procedures were performed in the oral cavity to 399 (34.3%): uvulectomy 41.8%, milk tooth extraction 33.7% and tonsillectomy 24.5%. Multinomial logistic regression showed strong association of uvulectomy with Tigray ethnicity. Milk teeth extractions were highest among girls, rural residence, Tigray and Amhara ethnicity. When procedures performed, children were under 1month (88.9% of tonsillectomies), under 6months (83.5% of uvulectomies) and 4-6months (54.3% of milk tooth extractions) of age. More than 97% for whom procedures performed were breast fed, and about 88% were from the northern part of the country. Taking into account the deep invasiveness of the procedures, they are assumed as one of the strong risk factors for MTCT of HIV during lactation.

Mother-to-Child HIV Transmission in a Cohort of Pregnant Women Diagnosed by Rapid HIV Testing at Tijuana General Hospital, Baja California, Mexico

This study evaluated an obstetrical program using rapid HIV testing for the prevention of mother-to-child HIV transmission (MTCT) in Baja California, Mexico. Between 2003 and 2005, 45 women in labor and 17 prenatal care women were HIV infected. Among labor patients, 14 (31%) delivered by cesarean section compared with 17 (100%) prenatal care patients (P < .001). Intravenous maternal zidovudine (ZDV) and infant oral ZDV were more frequently administered in prenatal care compared to labor patients: 94% versus 33% (P < .001) and 100% versus 79% (P < .001), respectively. All prenatal care women received combination therapy. All 10 HIV-infected infants were in the labor group, resulting in a MTCT rate of 23% (95% confidence interval [CI] 9.5-34.8) compared to 0% (95% CI 0-1.8; P < .001) among the prenatal care group. Five (50%) of the HIV-infected infants had an AIDS diagnosis and 2 (20%) died within 18 months of birth. Women diagnosed during labor had a high HIV MTCT and poor postnatal outcome.

Factors Associated with Mother‐to‐Child Transmission of HIV‐1 Despite a Maternal Viral Load &lt;500 Copies/mL at Delivery: A Case‐Control Study Nested in the French Perinatal Cohort (EPF‐ANRS CO1)

The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non-breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997-2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30+/-4 weeks adjusted for viral load, CD4(+) T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5-553; P<.001). Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4(+) T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.

An Imputation Method for Interval Censored Time-to-Event with Auxiliary Information: Analysis of the Timing of Mother-to-Child Transmission of HIV

The timing of mother-to-child transmission (MTCT) of HIV is critical in understanding the dynamics of MTCT. It has a great implication to developing any effective treatment or prevention strategies for such transmissions. In this paper, we develop an imputation method to analyze the censored MTCT timing in presence of auxiliary information. Specifically, we first propose a statistical model based on the hazard functions of the MTCT timing to reflect three MTCT modes: in utero, during delivery and via breastfeeding, with different shapes of the baseline hazard that vary between infants. This model also allows that the majority of infants may be immuned from the MTCT of HIV. Then, the model is fitted by MCMC to explore marginal inferences via multiple imputation. Moreover, we propose a simple and straightforward approach to take into account the imperfect sensitivity in imputation step, and study appropriate censoring techniques to account for weaning. Our method is assessed by simulations, and applied to a large trial designed to assess the use of antibiotics in preventing MTCT of HIV.

Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy

Over the past decade, significant advances have been made in the treatment of HIV-1 infection using both pharmacologic and nonpharmacologic strategies to prevent mother-to-child transmission (MTCT). Optimal prevention of the MTCT of HIV requires antiretroviral drugs (ARV) during pregnancy, during labor, and to the infant. ARVs reduce viral replication, lowering maternal plasma viral load and thus the likelihood of MTCT. Postexposure prophylaxis of ARV agents in newborns protect against infection following potential exposure to maternal HIV during birth. In general, the choice of an ARV for treatment of HIV-infected women during pregnancy is complicated by the need to consider the effectiveness of the therapy for the maternal disease as well as the teratogenic or teratotoxic potential of these drugs. Clinicians managing HIV in pregnancy need to discuss the potential risks and benefits of available therapy options so that mothers can make informed decisions in choosing the best treatment regimen for themselves and for their children.

HAART during pregnancy and during breastfeeding among HIV-infected women in the developing world: has the time come?

This editorial comment focuses upon the idea of offering HAART to all HIV-infected pregnant women including those in developing countries and considers the barriers or problems associated with this concept as well as the positive outcomes. It states that more data is needed but that a strategy would be to ensure that women with CD4 cell count below 350 cells/ml in resource-limited settings receive HAART that would then be continued after breastfeeding cessation for maternal health.

The change trend of mother-to-child transmission rate of HIV-1 during 2005-2007 in some areas of China

To explore the change trend of mother-to-child-transmission (MTCT) of HIV-1 in some areas in China. The investigation was conducted in 15 counties or districts of 4 provinces in China with relatively high HIV prevalence from January 2005 to June 2009. The data on the death and HIV-status of the babies born to HIV-positive mothers from January 2005-December 2007 in research sites were collected through 18-month following up after they were born. During the time that the research was conducted, there were 644 babies born to HIV-positive mothers who were followed up for 18 months. At the end of 18 months, full data were collected from 550 babies, 44 babies were lost to follow-up and 50 babies died. Among 550 babies who were followed up for 18 months, 53 babies were confirmed as HIV positive. The rate of MTCT of HIV-1 was 13.19% (24/182), 8.90% (17/191) and 6.78% (12/177) in 2005, 2006, 2007 respectively, which showed a descending trend yearly (chi(2) = 4.23, P < 0.05). Adjusted by the death data of the HIV-exposed children, it was found that during 2005-2007 the rate of MTCT of HIV-1 was 16.74%, 12.98%, 9.52% respectively, which was also descending year by year (chi(2) = 4.69, P < 0.05). Long-term, effective prevention of mother-to-child-transmission of HIV (PMTCT) could reduce the level of MTCT of HIV-1 year-by-year. In addition, using death data of HIV-exposed children to adjust the level of MTCT of HIV-1 is valuable to grade the effect of PMTCT.

Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1

BackgroundMother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1.Methods and FindingsTo investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011).ConclusionThese results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission.

Modeling vertical transmission of HIV: Imperfect vaccines can be of benefit

Reducing mother to child transmission (MTCT) of HIV in resource poor countries continues to be a major challenge. Here, we construct a hazard model to assess the effectiveness of combinations of HIV vaccine, Nevirapine (NVP), and HIV-specific monoclonal antibody (HIVAB) in reducing MTCT of HIV during the intrapartum and breastfeeding periods. The model shows that an intervention that uses three doses of vaccine with 30% initial immunity and 30% boost effect with subsequent doses (giving rise to maximum immunity approximately 66% with 3 doses) could reduce MTCT to 7.7% when used with NVP and to 5.9% when used with NVP and HIVAB. Using a vaccine with 50% initial immunity and 50% boost can reduce the rate to 4.3%. These results indicate that even an imperfect vaccine, when used in combination with other therapies, can be of considerable benefit in preventing MTCT in resource poor countries.

Tenofovir disoproxil fumarate in pregnancy and prevention of mother‐to‐child transmission of HIV‐1: is it time to move on from zidovudine?

Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic. In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required.

CD14+ cells are the main targets for HIV-1 infection in first trimester pregnancy human uterine mucosa

During the first trimester of pregnancy, HIV-1 mother-tochild transmission (MTCT) is relatively rare despite the permissivity of placental cells to cell-to-cell HIV-1 infection. The invasive placental cells interact directly with the decidual cells (cells of the maternal uterine mucosa during pregnancy) in the first months of pregnancy; however the role of the decidua in the control of HIV-1 transmission remains unknown. The decidua has a characteristic leukocyte population containing natural killer cells (dNK), antigen-presenting cells (dAPC) and T lymphocytes. The aim of this study was to determine whether decidual cells could be potential targets to HIV-1 and could thus represent a risk for HIV-1 MTCT in utero.

CCR2-64I Polymorphism Is Associated With Lower Maternal HIV-1 Viral Load and Reduced Vertical HIV-1 Transmission

Despite the relatively poor efficiency of HIV-1 infection via CCR2, a single nucleotide polymorphism in the CCR2 coding sequence that results in a valine to isoleucine change has been implicated as a host determinant of HIV-1 transmission and pathogenesis. Several studies have demonstrated an association between the CCR2-64I polymorphism and slower disease progression in adults.1 Its role in mother-to-child transmission (MTCT) of HIV-1 remains controversial, and its protective effect seems to vary depending on ethnicity and use of antiretroviral drugs for prevention of HIV-1 MTCT.2 The CCR2-64I variant is common in the Kenyan population, with a frequency of 25%, enabling us to evaluate associations between the CCR2-64I polymorphism and maternal HIV-1 viral load and to determine the effect of CCR2-64I on HIV-1 MTCT in a cohort in Nairobi.

Retrospective cohort study on the rate of mother-to-child transmission among mothers infected with human immunodeficiency virus type 1 through blood transfusion

To study the rate of mother-to-child transmission (MTCT) on HIV-1. All local residents from 8 townships in a region were screened for mothers who had a history of only one blood transfusion and 63 were found HIV-1 positive. A further study on these HIV-1 positive mothers and their children was conducted with the emphasis on the date of receiving blood transfusion, date and type of nationality, history regarding breastfeeding and so on. Sera specimens from 84 children born from 63 HIV-1 positive mothers were screened, using ELISA for HIV-1 antibody, and positive specimens were confirmed by Western-blot. The rate of MTCT was 32.1% (27/84) for children with all risk factors related to MTCT. Another 36.8% (7/19) were related to factors on intrauterine, intrapartum and breastfeeding, 35.7% (5/14) to intrapartum and breastfeeding factors, 14.3% (2/14) to intrauterine and intrapartum factors, 37.9% (11/29) to breastfeeding factor alone. By group combination analysis, the MTCT rate was 36.9% (24/65) with breastfeeding, 11.8% (2/17) with artificial feeding, and the former was significantly higher than the latter. HIV-1 MTCT rate among mothers caused by a single blood transfusion varied with different risk factors. Breastfeeding played an important role in MTCT, appeared in our study.

Role of β-Defensin-1 Polymorphisms in Mother-to-Child Transmission of HIV-1

Mother-to-child transmission (MTCT) of HIV-1, the main source of pediatric AIDS, is multifactorial. Defensins provide microbial barriers and function as effectors of innate immunity. This study investigated the relationship between genetic variants of beta-defensin-1 gene and MTCT of HIV-1. Three hundred children, 118 HIV-1 infected and 182 HIV-1 uninfected, born to HIV-1-infected mothers who had not undergone antiretroviral therapy during pregnancy, and 84 HIV-1-infected mothers were analyzed. The single nucleotide polymorphisms -44C/G (rs1800972) and -52G/A (rs1799946) were genotyped by TaqMan allelic discrimination assay and sequencing. Statistical analyses were performed using SNPStats and Bonferroni correction for multiple tests. In children, the -52GG genotype and the -44G/-52G haplotype had a protective role against HIV-1 infection [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.31 to 0.86, P = 0.03 and OR = 0.50, 95% CI 0.31 to 0.83, P = 0.014, respectively]. In mothers, the -52GG genotype and the -44G/-52G haplotype were associated with low levels of HIV-1 plasma viremia (<1000 copies/mL) and a lower risk of maternal HIV-1 transmission (OR = 0.14, 95% CI 0.03 to 0.67, P = 0.009 and OR = 0.23, 95% CI 0.08 to 0.66, P = 0.012, respectively). These results demonstrate a significant relationship between genetic variants of beta-defensin-1 gene, viral load, and MTCT of HIV-1, thus supporting a critical role of innate immunity in pediatric HIV-1 infection.