Prevention of mother-to-child transmission of HIV-1.

Several recently published randomized trials have demonstrated that a substantial proportion of the mother-to-child transmission of HIV-1 can be prevented by antiretroviral therapy late in gestation and at delivery to mother and infant. The cost implications of these findings are considerable for resource-poor settings. Preliminary data also suggest very low rates of transmission among mothers receiving maximally suppressive combination drug regimens. Prophylactic cesarean delivery has also been shown to reduce transmission in women not receiving antiretroviral agents, and may play a role in selected patients. The avoidance of breast feeding with infant formula supplementation is clearly protective against HIV-1 transmission, but may not improve infant survival in some poorer settings because of associated increases in other infectious diseases and malnutrition.     

Missed opportunities for prevention of mother-to-child transmission of HIV-1 in the NISDI Perinatal and LILAC cohorts

ObjectiveTo evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention.MethodsPregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006.ResultsOf 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7–2.6). Timing of transmission was in utero or intrapartum (n = 5), intrapartum (n = 2), intrapartum or early postnatal (n = 1), and unknown (n = 2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding.ConclusionEarly knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163.     

Immune-based approaches to the prevention of mother-to-child transmission of HIV-1: active and passive immunization

Despite more than 2 decades of research, an effective vaccine that can prevent HIV-1 infection in populations exposed to the virus remains elusive. In the pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in utero, at birth or in early life through breast milk require special consideration? This article reviews what is known about the immune mechanisms of susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and summarizes studies that have used passive or active immunization strategies to interrupt MTCT of HIV-1. Potentially modifiable infectious cofactors that may enhance transmission and/or disease progression (especially in the developing world) are described. An effective prophylactic vaccine against HIV-1 infection needs to be deployed as part of the Extended Program of Immunization recommended by the World Health Organization for use in developing countries, so it is important to understand how the infant immune system responds to HIV-1 antigens, both in natural infection and presented by candidate vaccines.     

Prevention of mother-to-child transmission of HIV-1: the role of cesarean delivery

The risk of mother-to-child transmission (MTCT) of HIV can be reduced through cesarean delivery prior to the onset of labor and prior to rupture of the membranes (elective cesarean delivery [ECD]). As a result of this evidence, the American College of Obstetricians and Gynecologists and the Department of Health and Human Services Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission developed guidelines recommending ECD for HIV-infected women with plasma viral loads of more than 1000 copies/mL. Since the release of the recommendations, an increase in ECD has been seen among HIV-infected women in the United States. This article discusses the evidence on efficacy of ECD, current recommendations in the United States, and risks and morbidity related to ECD. Although the benefit of ECD in preventing MTCT of HIV is substantial, some questions remain. Specifically, the benefit of ECD for women with very low viral loads or for women using combination antiretroviral regimens is unclear, as is the timeframe after onset of labor or rupture of membranes within which ECD will still confer preventive benefits.     

Strategies for prevention of mother-to-child transmission of HIV.

Over 90 per cent of paediatric HIV infections are maternally acquired, most of these in sub-Saharan Africa. Mortality trends underscore the humanitarian and ethical obligation for urgent global action to protect children from HIV. With the adoption of anti-retroviral therapy in pregnancy, mother-to-child transmission rates have declined to 4-6 per cent in the USA and other industrialised countries. In low-resource settings, where most of the children are continuously being exposed to HIV, the cost of anti-retroviral therapy is prohibitive. Very few developing countries apart from Botswana, Thailand and Brazil have national policies for integration of preventive anti-retroviral therapy in antenatal clinics. This paper reviews anti-retroviral and non-anti-retroviral interventions for prevention of mother-to-child transmission of HIV. To support the health of mothers as well, it supports the implementation of a comprehensive package of care in pregnancy and post-partum, such as access to antenatal and delivery services; anti-retroviral preventive therapy; malaria treatment; family planning; multivitamin, iron and folate supplementation; counselling on feeding options; post-natal care for the child and post-partum care for the mother, and calls for a strategy for advocacy, programme communication and community mobilisation.     

Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe

Objectives To document policies regarding the use of interventions to reduce risk of vertical transmission of human immunodeficiency virus (HIV) and assess the extent of changes since 1994.
Design A postal questionnaire survey and data from the European Collaborative Study (ECS), a prospective multi-centre cohort study.
Setting Fifty-four obstetric centres in 16 European countries.
Sample A questionnaire response from 54 obstetricians; 669 deliveries to HIV-infected women enrolled in the ECS from 1994 to 1997.
Main outcome measures Use of zidovudine during pregnancy, at delivery and to the neonate; caesarean section delivery rates; vaginal lavage; avoidance of breastfeeding; vertical transmission rate.
Results Zidovudine therapy to reduce vertical transmission is now widespread in Europe and routine in all but one centre surveyed, although regimens vary. In 11 (26%) centres elective caesarean section is offered to all HIV-infected women and a further nine (21%) have a policy of routine vaginal lavage. In all centres HIV-infected women are advised to avoid breastfeeding. In the ECS there has been a significant temporal decline in the vertical transmission rate with an increase in zidovudine use. More than 90% of women in the ECS who were delivered in 1997 received one or more components of zidovudine therapy; the rate of vertical transmission is 9% where zidovudine has been used, compared with 15% without use of zidovudine.
Conclusions Although the use of zidovudine to reduce vertical transmission is increasing in Europe and, with the avoidance of breastfeeding, is associated with a decline in vertical transmission, the success of these interventions will be limited by the uptake of antenatal screening.     

Elective cesarean delivery plus short-course lamivudine and zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus type 1

OBJECTIVE: The purpose of this study was to evaluate the effect of elective cesarean delivery plus a lamivudine-zidovudine prophylaxis regimen on non-breastfeeding mothers with human immunodeficiency virus type 1 and their infants. STUDY DESIGN: Forty-six antiretroviral-na?ve, pregnant women with human immunodeficiency virus type 1 were included. The prophylactic regimen was a lamivudine-zidovudine tablet (150 mg/300 mg) twice daily from week 34 of pregnancy until cesarean delivery at week 38 of gestation, preoperative intravenous zidovudine, and neonatal zidovudine syrup for 4 weeks. RESULTS: At weeks 34 and 38 of gestation, the median maternal viral loads were, respectively, 3.65 log(10) copies/mL (range, 2.34-4.70 log(10) copies/mL) and 2.51 log(10) copies/mL (range, 2.04-3.66 log(10) copies/mL; P<.001), respectively; the viral reduction was 1.12 log(10) copies/mL (range, -0.16-2.60 log(10) copies/mL), and the CD4(+) cell counts increased from 335 cells/mm(3) (range, 57-974 cells/mm(3)) to 420 cells/mm(3) (range, 84-1,083 cells/mm(3); P=.002). No mother or infant had a serious adverse event. Two infants were infected (4.3%; 95% CI, 0.5%-15.7%); 1 infant had intrapartum infection. CONCLUSION: Elective cesarean delivery plus short-course lamivudine-zidovudine is safe but does not eliminate mother-to-child transmission of human immunodeficiency virus type 1.     

HIV-1 and breastfeeding: biology of transmission and advances in prevention

Breastfeeding accounts for about 40% of mother-to-child transmission of HIV-1 worldwide and carries an estimated risk of transmission of 0.9% per month after the first month of breastfeeding. It is recommended that HIV-1-infected women completely avoid breastfeeding in settings where safe feeding alternatives exist. However, as replacement feeding is not safely available in many parts of the world, and because breastfeeding provides optimal nutrition and protection against other infant infections, there is intense ongoing research to make breastfeeding safe for HIV-1-infected mothers in resource-limited settings. More research is needed to determine the optimal duration of breastfeeding, optimal weaning practices, and which individual antiretroviral prophylactic regimen is best for HIV-1-infected mothers and their infants in a particular setting.     

Expression of HLA-G1 at the placental interface of HIV-1 infected pregnant women and vertical transmission of HIV

Objectives

The ability of Human Leucocyte Antigen-G (HLA-G) to inhibit the cytolytic effect to immunocompetent cell types, suggests that HLA-G has an immunomodulatory role. In view of this concept the objective of the study was to assess whether the Major Histocompatibility Complex -coded molecule HLA-G mRNA is a risk factor at the placental barrier in HIV-1 positive pregnant women.

Design

Placental HLA-G1 levels in HIV-1 infected mothers and viral loads in both mothers and their babies were performed on fifty-five participants.

Methods

Synthesis of complementary deoxyribose nucleic acid (cDNA) was performed using ribose nucleic acid (RNA) extracted from placental tissue samples. Amplification of cDNA using specifically designed primers complementary to the full length HLA-G1 isoform was quantified using real time-polymerase chain reaction (RT-PCR). Viral load assays (Amplicor Version 1.5, Roche Diagnostics) were performed on all plasma samples.

Results

HLA-G1 primers detected the full length isoform HLA-G1 PCR product at 86.5 °C. Logistic regression calculations indicated that the risk of babies becoming infected increased by 1.3 with every 1 unit increase in HLA-G1 expression. Female babies were 3.7 times more likely to become infected than male. There was a positive correlation between mothers’ log viral load and transmission of infection to the baby (p = 0.047; 95%CI 1.029–11.499).

Conclusion

Maternal viral load was a strong predictor of viral transmission. Placental HLA-G1 expression was up-regulated 3.95 times more in placentas of HIV-1 infected mothers with infected babies when compared to uninfected babies.     

The value of highly active antiretroviral therapy in the prevention of mother-to-child transmission of HIV.

Over 90% of the children infected with HIV globally were as a result of mother-to-child transmission. With a high prevalence of HIV among women of reproductive age and a high fertility rate in Nigeria, the prevention of mother-to-child transmission of HIV is an important strategy to curb the menace of HIV. This paper examines the value of highly active antiretroviral treatment in the prevention of mother-to-child transmission of HIV. Pregnant women attending the antenatal clinic of the University of Maiduguri Teaching Hospital were offered voluntary counselling and testing for HIV. Seropositive women who fulfilled the criteria for administration of antiretroviral drugs were offered a triple combination of nevirapine, stavudine and lamivudine in pregnancy. Women who did not fulfil the criteria were offered single dose nevirapine in labour. The newborn of all HIV-positive women were offered nevirapine suspension within 72 h of delivery. Overall transmission rate for women who had combination treatment was 9.1% which was lowered to zero level among those that had elective caesarean section and infant formula in addition to the drugs. Those who had single dose nevirapine in labour had a transmission rate of 33.3%. It is recommended that the single dose nevirapine be abandoned in favour of combination treatment.     

Efficacy of single dose nevirapine in prevention of mother to child transmission of HIV-1

Objective(s)

To evaluate the efficacy of single dose nevirapine in the prevention of mother to child transmission of HIV-1 in 30 HIV-1 infected parturients.

Material and Method(s)

This study was necessary since any study has not been conducted in an Indian population, were usually women are not offered antiretroviral therapy during pregnancy but only peripartum. East Go-davari District of Andhra Pradesh, India, has the highest prevalence (2.5%) of HTV-1 positive antenatal women, according to NACO estimations. Therefore, the study was conducted in Lutheran General Hospital, Rajahmundry, East Godavari District, Andhra Pradesh, India, at a 50-bedded hospital offering health care to people living with HIV/AIDS. One year prospective study with 30 Primigravidae infected with HTV-1, were planned for elective cesarean section. Single dose 200mg tablet was administered two hours prior to the cesarean section and all babies were given nevirapine syrup 2mg/kg within 72 hours of birth. Babies were tested for HIV-1 at one and two weeks of birth.

Result(s)

All the women were primigravidae. Nineteen babies born to these mothers tested positive for HTV-1 after two weeks, confirming the transmission rate to be 63.33% (95% CI of proportion 45.36%–78.15%). Thus, the efficacy of single dose nevirapine in preventing mother to child transmission was found to be 36.67%. Neonatal morbidity was more in those babies that were HTV positive. Two neonatal deaths occurred in two weeks and both babies were HTV-1 positive.

Conclusion(s)

Single dose nevirapine is associated with a lower efficacy in preventing mother to child transmission of HTV-1.     

Costs and benefits of multidrug, multidose antiretroviral therapy for prevention of mother-to-child transmission of HIV in the Dominican Republic

ObjectiveTo investigate whether costs of multidose antiretroviral regimens (MD-ARVs), including highly active antiretroviral therapy (HAART), for prevention of mother-to-child transmission (PMTCT) of HIV might be offset by savings gained from treating fewer perinatally acquired infections.MethodsRates of MTCT reported in the Dominican Republic among mother-infant pairs treated with single-dose nevirapine (SD-NVP; n = 39) and MD-ARVs (n = 91) for PMTCT were compared. Annual births to women infected with HIV were estimated from seroprevalence studies. Antiretroviral costs for both PMTCT and for HAART during the first 2 years of life (in cases of perinatal infection) were based on 2008 low-income country price estimates.ResultsRates of MTCT were 3.3% and 15.4% for the MD-ARV and SD-NVP groups, respectively (P = 0.02). Assuming that 5775 of 231 000 annual births (2.5%) were to HIV-positive women, it was estimated that 191 perinatally acquired infections would occur using MD-ARVs and 889 using SD-NVP. High costs of maternal MD-ARVs (HAART, US$914,760 versus SD-NVP, $1155) would be offset by lower 2-year HAART costs ($250,344 versus $1,168,272 for infants in the SD-NVP group) for the lower number of children with prenatally acquired infection (191 versus 889) associated with the use of MD-ARVs for PMTCT (net national saving $3168).ConclusionDespite the high costs, use of MD-ARVs, such as HAART, for PMTCT offer societal savings because fewer perinatally acquired infections are anticipated to require treatment.     

Insights into the mechanisms of vertical transmission of HIV-1. BIOMED2 Working Group on the in utero transmission of HIV-1

This paper is a summary of three oral presentations, as well as the ensuing discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three members of the European Biomed group on vertical transmission of HIV (G. Chaouat, F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D. Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the Pasteur Institute, France; Irène Athanassakis, University of Crete, Greece; Eva Maria Feny?, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such, this paper intends to be neither a review, nor an original article, but rather is an opinion paper discussing the working hypothesis of this network, as well as some of their recent results, which were presented at this meeting. The paper was issued at the request of the organizers of the meeting.     

穴位按压防治HIV母婴阻断新生儿喂养不耐受的疗效观察

目的观察穴位按压防治人类免疫缺陷病毒(HIV)母婴阻断新生儿喂养不耐受的临床效果。方法 2013年7月至2015年7月在广州市第八人民医院出生的HIV母婴阻断新生儿102例,随机分为观察组52例与对照组各50例。两组均出生后4h内即开始足月儿配方奶喂养,并于第一次吃奶同时开始给予奈韦拉平口服混悬液抗病毒阻断治疗,每次1.5mL,每日1次。根据新生儿的喂养耐受情况个体化调整奶量,期间常规监测血糖,如血糖偏低或经口喂养摄入能量不足者可联合静脉营养支持至经口喂养可满足其生长所需能量为止。观察组在对照组的基础上联合穴位按压。新生儿出生后24h且生命体征平稳,即可开始进行穴位按压,取穴:足三里、中脘、天枢、脾俞及胃俞,依次按压以上穴位(足三里及天枢为双侧同时按压),每个穴位按压时间先从每次1min开始,新生儿适应后,可逐渐延长至每次2min,每日2次。两组患儿在研究期间均不使用促胃肠动力药。观察喂养不耐受发生情况、每日奶量增加速度、完全经口喂养日龄及恢复出生体质量日龄。结果观察组奶量增加速度快于对照组,完全经口喂养日龄及恢复出生体质量日龄均早于对照组,差异均有统计学意义(P0.05)。观察组呕吐、腹胀、胃潴留及奶量增加困难发生率均低于对照组,差异均有统计学意义(P0.05)。结论穴位按压可有效防治HIV母婴阻断新生儿喂养不耐受的发生。     

Determinants of male involvement in the prevention of mother-to-child transmission of HIV programme in Eastern Uganda: a cross-sectional survey

Background  

Mother-to-child transmission of HIV (MTCT) accounts for over 95% of all paediatric HIV infections worldwide. Several studies have shown that male participation in the antenatal care of their spouses together with couple counselling and testing for HIV, increases use of the interventions for HIV prevention. The prevention programme of MTCT (PMTCT) was launched in Uganda in 2000 and Mbale in 2002. Less than 10% of the pregnant women accepted antenatal HIV testing at Mbale Regional Referral Hospital in 2003; couple counselling and testing for HIV was low. Therefore, we conducted the study to determine the level of male involvement and identify its determinants in the PMTCT programme.     

Cochrane评价:抗逆转录酶疗法降低艾滋病病毒母婴传播的危险度

1 背景。在母乳喂养人群中应该考虑到较长期使用尼维拉平(尤其结合早期断奶)的潜在价值，因为它能进一步降低母婴传播的危险度。现正在进行的对抗逆转录病毒联合疗法的评估具有重大意义，那些有能力开展此项治疗的国家可以立即从中受益。在那些资源贫乏的国家，仍应将可替代抗逆转录病毒联合疗法的有效、可负担、安全和可接受的其它降低母婴传播疗法的研究列入研究议程(UNAIDS／WHO)。