Prevention Of Perinatal HIV Transmission Research Articles

Prevention of Perinatal HIV Transmission in an Area of High HIV Prevalence in the United States

In 2014, the US Department of Health and Human Services modified the perinatal HIV management guidelines suggesting that women are considered low risk if they are living with HIV on antiretroviral therapy (ART) with HIV RNA ≤1000 copies per mL in late pregnancy and near delivery. In this population, it no longer recommended to administer maternal intrapartum intravenous zidovudine. In addition, for low-risk HIV-exposed infants (HEI), prophylaxis recommendation is 4 weeks of zidovudine after birth, whereas for high-risk HEI, it is 6 weeks of either a dual or triple therapy with zidovudine. This study was designed to help understand the use of these new perinatal HIV prevention interventions by evaluating the risk of perinatal HIV transmission in mother–infant pairs in a high HIV prevalence US area.In this study, researchers included 551 HIV-exposed infants (HEI) and 542 mothers living with HIV in the Washington, District of Columbia, area who were evaluated at Special Immunology Services in Children’s National Hospital between January 2013 and December 2017.A retrospective cohort analysis of these mother–infant pairs was completed, assessing a number of characteristics but, most notably, antiretroviral treatment during the pregnancy, HIV viral load at delivery, intrapartum zidovudine, delivery type (cesarean delivery versus vaginal), antiretroviral prophylaxis regimen for infant, antiretroviral prophylaxis duration for infant, and final HIV status of infant.The majority of mothers received antiretrovirals (95.5%), had HIV RNA ≤1000 copies per mL before delivery (81.9%), and received intrapartum zidovudine (65.5%). The majority of all HEIs were low risk (82.6); among these low-risk HEIs, slightly over one-half were delivered via cesarean delivery, and 62.9% received intrapartum zidovudine. In the study population, 9 infants acquired HIV perinatally and were all in the high-risk category, and not all of these infants were on dual or triple therapy with zidovudine.In this study, the researchers highlighted that the newer perinatal HIV recommendations have not been completely adopted because they showed 62.9% of the low-risk patients received intrapartum zidovudine, despite it no longer being recommended. Furthermore, of the 9 infants who acquired HIV perinatally, they were all considered high risk, but 6 were not on a dual or triple therapy. Certain factors can affect the decision to initiate combination antiretroviral therapy; however, in this study, it is suggested there were possible missed opportunities for use of this treatment as a prevention of perinatal HIV transmission.As the field of HIV and perinatal treatment of mother–infant pairs evolves and new recommendations emerge, it is essential the medical community strives to follow these recommendations as closely as possible to decrease perinatal HIV transmission. Adhering to the recommendations would minimize the medication exposures to those low-risk patients, while optimizing the antiretroviral regimen for high-risk HEIs, leading to the lowest perinatal HIV-transmission possible.

David Katzenstein and James Hakim-In Memoriam.

The world lost two wonderful doctors who devoted their lives to the fight against HIV/AIDS in Africa. Ironically, they both died of COVID-19 within hours of each other in late January in Zimbabwe. David Katzenstein, MD, began his career in the early 1980 s working with underserved populations at a Native Tribal clinic in New Mexico and with persons suffering from AIDS at the Haight Ashbury Clinic in San Francisco, conducted CMV research at the University of Minnesota, and then took a position working as a microbiologist at the University of Zimbabwe in Harare between 1985 and 1987. In 1989, David joined the faculty at Stanford University where he remained until his retirement in 2017. Dr Katzenstein, led many important clinical and translational research studies related to HIV. With his colleagues in the AIDS Clinical Trials Group (ACTG), he led studies that resulted in the approval of life-saving antiretroviral medications. David dedicated a major portion of his academic endeavors to study HIV drug resistance, serving as director of one of the Virology Specialty Laboratories for the ACTG for many years. He was a protocol team member and leader on several ACTG studies and served on numerous ACTG committees, including the Performance Evaluation Committee and the original Virology Committee. He was co-chair of ACTG 384 that dealt with protease and/or non-nucleoside reverse transcriptase inhibitors, and was one of the first investigators to call attention to the issues of drug resistance in Africa. Recognizing the disparate impact of HIV in resource limited settings, David was a pioneer in Global HIV Research, in the fields of perinatal HIV transmission prevention, and studying different approaches to optimize antiretroviral treatment and laboratory monitoring in various settings around the world. He worked diligently to bring laboratory technology to Zimbabwe. Following his retirement from Stanford in 2017, David became the director of the Biomedical Research Training Institute in Zimbabwe where he led the molecular diagnostics laboratory to support laboratory monitoring of community-based treatment programs. In all his work, David engaged researchers and trainees from different parts of the world. Generous with his time, effort and ideas, David was a cherished mentor for many young and mid-career physicians and scientists, now scattered throughout different academic institutions and agencies in the U.S. He nurtured careers of clinicians, basic and social scientists, while encouraging multidisciplinary efforts to tackle the global HIV pandemic. He worked tirelessly and with great joy, giving of himself without reserve. James Gita Hakim, MRCP-UK, Professor of Medicine, University of Zimbabwe College of Health Sciences, to COVID-19. Dr Hakim was an accomplished investigator who made seminal contributions in HIV treatment and prevention research. He was known internationally for his accomplishments as a research leader, a builder of African research capacity, a leader of modernizing medical education in Africa, and as a mentor of young African investigators. Dr Hakim was at the forefront of clinical research on HIV/AIDS in Africa for over 20 years. He founded the University of Zimbabwe Clinical Research Centre (UZ-CRC) in 2001 as a site for international clinical trials on HIV treatment and prevention. He was a leader in pivotal international clinical trials including the landmark HIV ‘treatment as prevention’ trial HPTN 052, the MRC-funded “Development of Anti-Retroviral Therapy in Africa” (DART) trial, and the ACTG “Prospective Evaluation of Antiretroviral Therapy in Resource Limited Settings” (PEARLS) study. These studies contributed to the knowledge needed for successful implementation of antiretroviral therapy in southern Africa. Dr Hakim was as Principal Investigator of the University of Zimbabwe's program, the Medical Education Partnership Initiative (MEPI) which serves as a model for medical education in Africa. He was as a representative on the International AIDS Society (IAS) Governing Council from 2016 to 2020 and on the World Health Organization Guidelines Review Committee, the UNAIDS Advisory Committee, and on program committees for IAS Conference on HIV Science, the Conference on Retroviruses and Opportunistic Infections (CROI). Dr Hakim was Co-chair of the World AIDS Conference, Amsterdam, Netherlands in 2018. James Hakim's life demonstrated how investment in biomedical research and modern medical education can pay large dividends and be transformative for Africa. The world is better for the lives you lived, David and James. May light perpetual shine upon you.

Frequency of differential placental transfer to twins of maternal antiretroviral medications

BackgroundPlacental passage of drugs in twins is poorly understood, and is unknown regarding antiretrovirals (ARVs). In the event of large differences in the exposure of 2 twins to the same maternal therapy, this could have a clinical impact in terms of prevention of perinatal HIV transmission or adverse effects. ObjectiveTo describe the frequency of differential transplacental passage of antiretrovirals between twins. Study designThe study was performed retrospectively, on data from women included in a multicenter perinatal HIV cohort study. All twin pairs for which the mother received antiretroviral therapy and for which drug concentrations in both of the umbilical cords after cord clamping at delivery were studied. We considered that a difference in concentrations of more than 50 % between twins was a substantial difference (ratios below 0.67 or above 1.50). ResultsWe analyzed 29 twin pairs, 27 dichorionic and 2 monochorionic diamniotic. Cord blood concentrations differed between the 2 twins by more than 50 % for at least one ARV in 9 twin pairs, 8 dichorionic and 1 monochorionic. Discordant concentrations were observed in one or more cases for several nucleoside reverse transcriptase inhibitors (tenofovir, emtricitabine, lamivudine, zidovudine) and protease inhibitors (atazanavir, lopinavir, saquinavir et ritonavir); within individual twin pairs placental transfer was discordant for one or more ARVs, but identical for others. ConclusionConcentrations differed in nearly one third of twin pairs. This may be due to interindividual genetic variability of placental transporters between dizygotic twins as well as physiological differences between twins.

Prevention of Perinatal HIV Transmission in an Area of High HIV Prevalence in the United States

To evaluate the uptake of perinatal HIV preventive interventions by the risk of perinatal HIV transmission in mother-infant pairs in a high-HIV prevalence area in the US. This was a retrospective cohort study of mother-infant pairs with perinatal HIV exposure during 2013-2017 managed at a subspecialty pediatric HIV program in Washington, DC. We collected demographic data, maternal HIV history, delivery mode, maternal and infant antiretroviral drug (ARV) use, and infant HIV test results. We compared the uptake of recommended preventive interventions in low-risk (ie, mothers on antiretroviral therapy [ART] with viral suppression) and high-risk (mothers without ART or viral suppression) mother-infant pairs using the Pearson chi-square, Fisher exact, and Wilcoxon rank-sum tests and logistic regression. We analyzed 551 HIV-exposed infants (HEIs) and 542 mothers living with HIV. The majority of mothers received ARVs (95.5%), had HIV RNA ≤1000 copies/mL before delivery (81.9%), and received intrapartum zidovudine (ZDV; 65.5%). The majority of all HEIs were low risk (82.6%) and received postpartum ARVs (98.9%). Among the low-risk infants, 53.2% were delivered via cesarean delivery (CD), and 62.9% and 96.5% were administered intrapartum and postpartum ZDV, respectively. Among high-risk infants, 84.4% were delivered via CD, 78.1% received intrapartum ZDV, and 62.5% received combination ART. Nine high-risk infants acquired HIV perinatally. In an area of high HIV prevalence in the US, a large proportion of low-risk HEIs received intrapartum ZDV and were delivered via CD. We also observed missed opportunities for the prevention of perinatal HIV transmission.

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial

Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.

The multi-country PROMOTE HIV antiretroviral treatment observational cohort in Sub-Saharan Africa: Objectives, design, and baseline findings.

BackgroundThe PROMOTE study aims to measure long-term antiretroviral treatment (ART) safety and adherence; compare HIV disease progression; assess subsequent adverse pregnancy outcomes; evaluate effect of ART exposure on growth and development in HIV-exposed uninfected children; and assess long-term survival of mothers and children. This report primarily describes cohort characteristics at baseline to better understand long-term outcomes.Methods and findingsThis is a prospective study. HIV-infected mothers and their children originally recruited in a multisite randomized clinical trial for prevention of perinatal HIV transmission were re-enrolled in PROMOTE. A total of 1987 mothers and 1784 children were enrolled from eight sites in Uganda, Malawi, Zimbabwe and South Africa. Most women (≥75%) reported being married in Malawi and Zimbabwe compared to low proportions in South Africa (4.4% in Durban and 15% in Soweto), and 43.5% in Uganda (p<0.001). There were variabilities in contraceptive practices: injectable contraceptive was the commonest reported method (40.9% overall); implant was the second commonest (15.7% overall); oral contraceptives were common in Zimbabwe; and tubal ligation was common in Malawi and South Africa. At baseline, 97.8% of women reported currently using ART; 96.4% were in WHO clinical class 1 or 2; median CD4 cell count was 825 cells per uL; and viral load was undetectable in 1637 (~85%) of the women. Approximately, 14% of women did not inform their primary partners of their own HIV status, 18% reported that they knew their partners were not HIV tested, and 9% did not know if partner was tested. Overall mean age of children at enrollment was 3.5 years; and 5.7% and 25.0% had weight-for-age and height-for-age z-scores <2 standard deviations, respectively.ConclusionsThese baseline data show high adherence to ART use. However, issues of HIV disclosure and reproductive intentions remain important. In addition to ART and ensuring high adherence, other preventive measures should be included.

Trends in Neonatal Prophylaxis and Predictors of Combination Antiretroviral Prophylaxis in US Infants from 1990 to 2015.

Postnatal antiretroviral (ARV) prophylaxis for infants born to women with HIV is a critical component of perinatal HIV transmission prevention. However, variability in prophylaxis regimens remains and consistency with guidelines has not been evaluated in the United States. We evaluated trends over time in prophylaxis regimens among 6386 HIV-exposed uninfected (HEU) infants using pooled data spanning two decades from three US-based cohorts: the Women and Infants Transmission Study (WITS, 1990-2007), Pediatric AIDS Clinical Trials Group (PACTG) 219C (1993-2007), and the PHACS Surveillance Monitoring of ART Toxicities (SMARTT) study (2007-2015). We also identified maternal and infant risk factors for use of combination prophylaxis regimens (≥2 ARVs) and examined consistency with US perinatal guidelines. We found that receipt of combination prophylaxis between 1996 and 2015 ranged from 2% to 15%, with a consistent median duration of 6 weeks. Infants whose mothers had lower CD4 T-cell counts, higher viral load (VL), no antepartum ARVs, age <20 years at delivery, and Cesarean delivery had significantly higher rates of combination prophylaxis, while infants born 2006-2010 (vs. 2011-2015), who were Hispanic or with lower maternal education levels, had significantly lower rates. Predictors for combination prophylaxis varied over time, with the strongest associations of maternal VL in later birth cohorts. While use of combination prophylaxis increased over time, only 50% of high-risk infants received such regimens in 2011-2015. In conclusion, HEU infants at higher risk of HIV acquisition are more likely to receive combination neonatal prophylaxis, consistent with US guidelines. However, substantial variability remains, and infants at higher risk often fail to receive combination prophylaxis.

Successful prevention of perinatal HIV transmission utilizing direct observation therapy in the setting of Acquired Immunodeficiency Syndrome (AIDS) and progressive multifocal leukoencephalopathy.

We report a case of a 22-year-old G1P0010 African-American female with poorly controlled perinatally acquired HIV/AIDS and recent diagnosis of progressive multifocal leukoencephalopathy (PML) by magnetic resonance imaging (MRI). She presented to a tertiary care facility for prenatal care and direct observation therapy after poor medication adherence during pregnancy. After multiple attempts at outpatient ART management, the patient was admitted at 35 weeks' gestation for direct observation therapy for both antiretroviral therapy and anti-seizure medication. Viral load at that time was 22,487 copies/mL and she was admitted and started on a salvage regimen which included: dolutegravir, tenofovir disoproxil fumarate/emtricitabine, darunavir, ritonavir, and trimethoprim/sulfamethoxazole for Pneumocystis jirovecii prophylaxis. The patient remained on direct observation therapy throughout her two-week hospital stay with final viral load of 1211 copies/mL, CD4 284/uL at time of delivery at 37 weeks' gestation, with minimal seizure activity. The infant received postnatal antiretroviral therapy including three doses of zidovudine and nevirapine with negative HIV PCR at birth, 2, 4, and 6 months postpartum and is currently HIV negative.

Role of nucleoside transporters in transplacental pharmacokinetics of nucleoside reverse transcriptase inhibitors zidovudine and emtricitabine

IntroductionZidovudine (AZT) and emtricitabine (FTC) are effective and well tolerated antiretroviral drugs, routinely used in the prevention of perinatal HIV transmission. However, precise mechanism(s) involved in their transfer from mother to fetus are not fully elucidated. Since both drugs are nucleoside analogues, we hypothesized that the mechanisms of their transplacental passage might include equilibrative nucleoside transporters, ENT1 and/or ENT2. MethodsTo address this issue, we performed in vitro accumulation assays in the BeWo placental trophoblast cell line, ex vivo uptake studies in fresh villous fragments isolated from human placenta and in situ dually perfused rat term placenta experiments. ResultsApplying this complex array of methods, we did not prove that ENTs play a significant role in transfer of AZT or FTC across the placenta. DiscussionWe conclude that the transplacental passage of AZT and FTC is independent of ENTs. Disposition of either compound into the fetal circulation should thus not be affected by ENT-mediated drug-drug interactions or placental expression of the transporters.

Long-term administration of tenofovir or emtricitabine to pregnant rats; effect on Abcb1a, Abcb1b and Abcg2 expression in the placenta and in maternal and fetal organs.

Tenofovir and emtricitabine are very effective and well-tolerated antiretrovirals representing current backbone of the antiretroviral combination regimens for the prevention of perinatal HIV transmission. The aim of our study was to determine whether tenofovir or emtricitabine administered in long-term fashion affect expression of two widely described pharmacokinetic determinants, P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), in maternal or fetal biological tissues. For this purpose, pregnant Wistar rats were administered tenofovir (2.25 mg/kg/day), emtricitabine (3.5 mg/kg/day) or saline i.m. for 10 days (from the 12th to 21st gestation day). On the 22nd day, the placenta and maternal/fetal intestine, brain, kidneys and liver were sampled and analysed for Abcb1a, Abcb1b and Abcg2 expression; placental and newborns' weights were also monitored. We found that long-term application of tenofovir or emtricitabine did not significantly affect expression of Abcb1a, Abcb1b and Abcg2 in either maternal or fetal organs. However, tenofovir administration significantly increased placenta-to-birthweight ratio, a strong indicator of various diseases occurring later in life. Our data broaden current knowledge on safety profile of tenofovir and emtricitabine use in pregnancy. Nevertheless, further research in other mammal species, including humans, is important to fully elucidate this issue.

HIV EPIDEMIC AMONG WOMEN OF REPRODUCTIVE AGES IN OSH REGION OF KIRGHIZ REPUBLIC

Study objective: To determine the current epidemiological characteristics of HIV infection among women of reproductive ages for developing measures for timely prevention of perinatal HIV transmission in Osh Region, one of major territories of Kirghizstan. Materials and methods: Monthly reports about testing of different populations for HIV (Form 4), official statistical reports about HIV registering in 2000-2014 (Form 4a), charts of the epidemiological studies in the foci of HIV outbreaks, and charts of dispensary follow-up of HIV-infected women were used. Results: An increase in HIV prevalence among pregnant women and their infants was revealed. Novel approaches to preventive intervention with account of the state policy in gender issues must be priority trends in HIV/AIDS prevention.

Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission: Executive Summary

ObjectiveThis guideline reviews the evidence relating to the care of pregnant women living with HIV and the prevention of perinatal HIV transmission. Prenatal care of pregnancies complicated by HIV infection should include monitoring by a multidisciplinary team with experts in this area. OutcomesOutcomes evaluated include the impact of HIV on pregnancy outcome and the efficacy and safety of antiretroviral therapy and other measures to decrease the risk of vertical transmission. EvidencePublished literature was retrieved through searches of PubMed and The Cochrane Library in 2012 and 2013 using appropriate controlled vocabulary (HIV, anti-retroviral agents, pregnancy, delivery) and key words (HIV, pregnancy, antiretroviral agents, vertical transmission, perinatal transmission). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to June 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. ValuesThe quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Accelerating prevention of mother-to-child transmission of HIV: Ten-year experience of Universal Antenatal HIV Testing Programme in a low HIV prevalence setting in Hong Kong

Hong Kong has a low prevalence of HIV infection at less than 0.01%. Universal Antenatal HIV Testing Programme (UATP) was launched in all public antenatal units in September 2001. In 2008, voluntary rapid HIV testing was introduced in all public labour units to fill up the gap for pregnant women without HIV testing during the antenatal period. This study evaluated the performance of UATP and rapid HIV testing with indicators. From September 2001 to December 2011, process and outcome indicators for monitoring and evaluation were collected from the service providers in the form of monthly return of workload statistics and case-based statistics of each identified HIV-positive pregnancy via reporting forms. A total of 479,160 antenatal HIV tests and 2,675 rapid tests were performed in the study period. The acceptance rate for UATP and rapid HIV testing was 98% and 80.4% respectively. With the implementation of rapid HIV testing in January 2008, the proportion of pregnant women with HIV status discerned before delivery increased from 84.9% in 2006 to over 99.5% since 2008. The HIV prevalence in UATP and rapid HIV testing was 0.02% and 0.1% respectively. Fifty-three (68%) out of 78 HIV-infected pregnant women identified from the programme have delivered locally. Forty-three (81%) of them delivered by caesarean section and 50 (94%) of them were given antiretrovirals for intervention. Only three children born before the implementation of rapid HIV testing were HIV-infected. In conclusion, UATP and its rapid HIV testing component have been highly accepted and effective in the prevention of perinatal HIV transmission in Hong Kong.

Fever and Rash in an 8-month-old Girl

Fever and Rash in an 8-month-old Girl

Antiretroviral strategies for the treatment of pregnant HIV+ women and prevention of perinatal HIV transmission in Dodoma, Tanzania: AMANI Study

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients

Importance of the field: HIV-infection has become a chronic disease in paediatric patients with the potential for long-term survival and exposure to antiretroviral (ARV) therapies for 2 decades longer than HIV-infected adults. On the other hand, the administration of ARV to HIV-infected pregnant women has greatly increased both treatment of HIV infection and prevention of perinatal HIV transmission. Therefore, researches aiming to evaluate the safety of ARV therapies in HIV-infected children as well as in HIV-uninfected infants born to HIV-infected mothers are emerging as a new challenge and urgent priority.Areas covered in this review: The purpose of this review is to describe some of the more concerning metabolic complications associated with ARV in paediatric population: hyperlactataemia (HLA) syndromes, body shape abnormalities, disorders of glucose homeostasis and dyslipidaemia in HIV-infected children and adolescents. Frequency, risk factors, clinical findings, prevention and intervention strategies of the previously described abnormalities are discussed in depth.What the reader will gain: This review covers our current understanding of HLA syndromes in ARV-exposed uninfected infants born to HIV-infected mothers.Take home message: Prevention of these metabolic complications should assume prominence and future researches should address several of the existing treatment gaps.

Risk factors of preterm delivery in HIV‐infected pregnant women receiving zidovudine for the prevention of perinatal HIV

Several studies have shown that preterm delivery, a primary cause of perinatal mortality and morbidity, is more frequent in HIV-positive women. This study aimed to determine factors associated with prematurity in HIV-infected women and identify risks for which specific interventions could be targeted. Data were prospectively collected in a clinical trial assessing the efficacy of different zidovudine prophylaxis durations for the prevention of perinatal HIV transmission in Thailand. Characteristics associated with prematurity - delivery before 37 weeks--were assessed using univariate and multivariate logistic regression and were subsequently used to identify subgroups of women at risk. Among 979 women, independent prematurity risk factors were: viral load <3.5 or >4.5 log copies/mL; hemoglobin > 11.5 g/dL; weight gain <0.25 kg/week; and body mass index <20 kg/m2. These factors allowed us to define four subgroups with an expected probability of prematurity increasing from 3% to 30%. The two subgroups with the highest expected probability of prematurity were considered to be 'at risk' as opposed to the two lowest (odds ratio = 2.6, 95% confidence interval: 1.7-4.0) and the sensitivity and specificity of the prediction were 51% and 71%, respectively. In this study, four risk factors of preterm delivery were identified allowing the identification of subgroups at increasing risk of prematurity. Adequate nutrition and the provision of highly active antiretroviral therapy during pregnancy as recommended by the World Health Organization for the prevention of perinatal transmission for immunocompromised women in resource-constrained countries may reduce the risk of premature delivery.

Disparity in Hospital Utilization of Rapid HIV-1 Testing for Women in Labor with Undocumented HIV Status

The implementation of rapid HIV-1 testing for women in labor with undocumented HIV status is an essential tool for the prevention of perinatal HIV transmission. Unfortunately, practices of rapid HIV testing for women with unknown HIV status in labor have not been studied. We evaluated the utilization of rapid HIV testing prior to and after implementation of CDC recommendations as well as factors that may affect the utilization rate. participants were randomly selected from all deliveries (n = 2,359) six months prior to (n = 422) and after (n = 403) hospital implementation of the rapid HIV testing protocol. We reviewed prenatal and labor/delivery records to identify HIV testing history during pregnancy and HIV status at admission; we studied Rapid HIV testing utilization in respect to the implementation of the CDC recommendation; and we analyzed maternal sociodemographic and perinatal factors in association with rapid HIV testing utilization. Unknown HIV status at admission was recorded for 22.0% of women who gave birth prior to, and 18.1% after, implementation of the hospital policy due to either no offering or no acceptance of HIV testing during the pregnancy. Among those eligible for rapid HIV testing, 7.6% were tested prior to, and 9.6% were tested after, implementation of the new policy. As compared with tested women, women not tested were more likely to be white, married, and to have received prenatal primary care from a private physician. We found that low utilization of rapid HIV-1 testing for women in labor with undocumented HIV status is mostly associated with the sociodemographic inequality of the population of women served. Continuous education of health care providers and a systematic review of rapid HIV testing utilization in the hospital setting are needed in order to achieve successful implementation of the current CDC recommendations.

Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: possibility to further decrease transmission?

To evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. Evaluation of women who participated in a 1996-1997 perinatal HIV transmission prevention trial in Thailand. In this nonbreastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0-6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0-8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log(10)copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). We found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission.

Expanding HIV Treatment Options in Pregnancy

In late 2007, the U.S. Public Health Service released updated guidelines for the prevention of perinatal HIV transmission (ACC Jan 14 2008). However,