Mother-to-child transmission of HIV infection and its prevention

An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usually in highly active combinations), elective caesarean section and avoidance of breastfeeding, and where infected women are identified before or in pregnancy and have access to these interventions, risk of MTCT is now below 1-2%. However, prompt identification of pregnant women with HIV infection remains pressing in many developed countries; additionally, concerns have arisen regarding adherence to complex treatment regimens in pregnancy and the potential impact of HIV drug resistance. More disturbingly, most HIV-infected women live in developing countries where many pregnant women even when tested do not return for their HIV results for a variety of reasons including stigma, and where most, if not all, strategies for prevention of MTCT have been of limited accessibility and/or feasibility. However, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and other initiatives including pharmaceutical companies' donation programmes and generic antiretroviral drug production have made prevention of MTCT in resource-poor settings an increasingly realistic goal, coupled with new evidence from clinical trials on the efficacy of abbreviated regimens of antiretroviral prophylaxis, including combination therapy, to prevent MTCT. Research is additionally focussing on reducing the risk of postnatal transmission through breastfeeding, with exclusive breastfeeding, early cessation and antiretroviral prophylaxis to breastfeeding women or breastfed infants under investigation. However, the key to prevention of paediatric HIV infections is adequate prevention of infection in women of reproductive age.     

International perspectives, progress, and future challenges of paediatric HIV infection

Paediatric HIV infection is a growing health challenge worldwide, with an estimated 1500 new infections every day. In developed countries, well established prevention programmes keep mother-to-child transmission rates at less than 2%. However, in developing countries, where transmission rates are 25-40%, interventions are available to only 5-10% of women. Children with untreated natural infection progress rapidly to disease, especially in resource-poor settings where mortality is greater than 50% by 2 years of age. As in adult infection, antiretroviral therapy has the potential to rewrite the natural history of HIV, but is accessible only to a small number of children needing therapy. We focus on the clinical and immunological features of HIV that are specific to paediatric infection, and the formidable challenges ahead to ensure that all children worldwide have access to interventions that have proved successful in developed countries.     

Preventing mother-to-child transmission of HIV-1 in Africa in the year 2000

OBJECTIVES: Various approaches to preventing mother-to-child transmission (MTCT) of HIV have recently been, or are being, evaluated in developing countries, especially in Africa. New findings from these trials are now becoming available, the implications of which, for population-based intervention programmes, need urgent consideration. METHOD: A critical review of 18 randomized trials and other relevant studies from developing and industrialized countries. RESULTS: Most African results relate to trials of antiretroviral agents (ARV). They demonstrate efficacy in reducing transmission in the first 6 months of life with short regimens of zidovudine (ZDV), with or without lamivudine (3TC), and nevirapine (NVP) alone. Preliminary results suggest the long-term efficacy of zidovudine. Antiseptic and nutritional interventions have been shown to reduce maternal and infant mortality and morbidity but not MTCT of HIV. HIV confidential voluntary counselling and testing for pregnant women, a short regimen of peripartum ARV with alternatives to breastfeeding such as early weaning or breast milk substitutes from birth currently represent the best option to reduce MTCTof HIV in Africa. However, the prevention of postnatal transmission requires further research, particularly in view of the consequences of different feeding options and the possibility of post-perinatal exposure prophylaxis of newborns with ARV. Issues relating to the implementation of currently validated strategies are discussed.     

HIV in pregnancy: evolution of clinical practice in the UK

Prior to the introduction of interventions reducing mother-to-child transmission of HIV-1 natural history data reports vertical transmission rates in the order of 25%. The risk of transmission from mother-to-child has been associated with advanced maternal HIV disease, maternal plasma HIV viral load and CD4 lymphocyte count, mode of delivery, length of rupture of membranes, prematurity and breast feeding. During the last 10-15 years the introduction of prelabour cesarean section, formula feeding and antiretroviral therapy has reduced transmission to less than 1% for pregnant women in the UK who are aware of their HIV status. Attention is now turning to the minimization of possible drug side effects for both mother and infant as women are increasingly conceiving on combination antiretroviral therapy. The evolution of current UK guidelines on the prevention of mother-to-child transmission of HIV-1 are discussed.     

Children with HIV: improved mortality and morbidity with combination antiretroviral therapy

PURPOSE OF REVIEW: Advances in the management of children with vertical HIV-1 infection in the developing and developed worlds are discussed in reference to literature published in 2003/4. Studies in mother-to-child transmission are beyond the scope of this review. RECENT FINDINGS: Improvements in mortality and morbidity from HIV-1 infection following combination antiretroviral therapy are extremely encouraging. There is an increase in the understanding of the immune response to HIV-1 in infants and children and a possible future role for immunomodulatory therapies. Preliminary data are available on the timing of initiation of antiretroviral therapy, the optimization of drug combinations and the clinical interpretation of genotypic resistance testing and therapeutic drug monitoring. Evidence is emerging that early antiretroviral therapy can protect the central nervous system in infants. In resource-limited settings, mortality and morbidity remain extremely high but low-cost health interventions such as prophylactic co-trimoxazole can reduce mortality prior to the expansion of antiretroviral therapy programmes. SUMMARY: Further randomized controlled trials assessing antiretroviral therapy combinations with a sustained virological/immunological response with minimal toxicities are required. The roles of therapeutic drug monitoring and resistance testing require further elucidation. The expansion of antiretroviral therapy programmes is essential for children with HIV living in resource-limited settings.     

Strategies to prevent mother-to-child transmission of HIV

PURPOSE OF REVIEW: This review describes recent advances in the prevention of mother-to-child transmission, focusing on the use of antiretroviral treatment strategies in pregnancy, and discusses the emergence of viral resistance following the use of nevirapine to prevent mother-to-child transmission. RECENT FINDINGS: Mother-to-child transmission has been dramatically reduced in developed countries by the use of antiretroviral treatment and avoidance of breastfeeding. Highly active antiretroviral therapy use in pregnancy is recommended for women who require ongoing treatment, and, where available, is also very effective in reducing mother-to-child transmission in women with higher CD4 counts. The addition of a maternal and infant nevirapine dose to antenatal zidovudine can reduce transmission to below 5%, approximately half the transmission rate that can be achieved by single-dose nevirapine alone. The emergence of resistant virus following nevirapine use is a concern, occurring in up to 60% of mothers and 50% of infants following a single dose. Addition of zidovudine and lamivudine for 4-7 days postpartum can reduce the risk of resistance to 10%. SUMMARY: There is broad consensus on an approach to preventing mother-to-child transmission, which provides antiretroviral treatment in pregnancy and beyond to those women who need it, and an effective prophylactic regimen for those who do not yet need treatment, These regimens include highly active antiretroviral therapy, where available, a zidovudine-plus-nevirapine regimen in other settings, or nevirapine alone where this is all that is possible. More work is needed on the impact of nevirapine resistance and on reducing breast-milk transmission.     

Cost-effectiveness analysis of infant feeding strategies to prevent mother-to-child transmission of HIV in South Africa

Despite increasing availability of perinatal interventions to prevent mother-to-child transmission (MTCT) of HIV in South Africa, MTCT remains high due to breastfeeding. To inform policy decisions in the country, cost-effectiveness of alternative infant-feeding interventions was conducted. Mathematical modelling was used to simulate post-natal transmission and mortality due to infant feeding in a hypothetical cohort of 1 000 HIV-exposed infants. Lifetime costs to the health system were calculated for each strategy. Interventions compared with current practice were: increasing coverage of extended nevirapine prophylaxis (ENP) to infants from 30% (base case) to 60% without changing current feeding practices; actively supporting breastfeeding with ENP to infants for 12 months; and actively supporting exclusive formula (replacement) feeding for 6 months. HIV-free survival at 24 months and disability-adjusted life years (DALYs) averted were estimated for typical rural and certain urban settings. Base-case analysis revealed that expanding coverage of nevirapine prophylaxis with breastfeeding is cost-saving and improves HIV-free survival. Changing feeding practices is beneficial, depending on context. Breastfeeding is dominant (less costly, more effective) in rural settings, whilst formula feeding is a dominant strategy in urban settings. Cost-effectiveness was most sensitive to proportion of women on lifelong antiretroviral therapy (ART) and infant mortality rate (IMR). When >55% of women are on ART, breastfeeding dominates in the urban settings modelled, whilst formula feeding is cost-effective in rural settings when IMR ≤ 45/1000. The study concludes that strategies to support breastfeeding are essential. Strengthening health systems is critical to ensure optimal nevirapine delivery during breastfeeding. A case can be made for formula feeding or breastfeeding in HIV-infected women in specific contexts.     

The infant feeding choices and experiences of women living with HIV in Kinshasa, Democratic Republic of Congo

HIV transmission through breastfeeding is a significant public health challenge. While breastfeeding provides important nutrition, and results in reduced morbidity and mortality, there is a risk of HIV transmission through breastfeeding. International prevention of mother-to-child transmission (PMTCT) guidelines recommend exclusive breastfeeding for six months among HIV-infected women on antiretroviral therapy. Promoting exclusive feeding has proved difficult in settings where mixed feeding is a cultural norm. Understanding the factors that influence HIV infected women's infant feeding choices and practices is critical to promoting adherence to PMTCT guidelines. We conducted in-depth interviews with 40 HIV+ pregnant and post-partum women in Kinshasa, Democratic Republic of Congo to understand their infant feeding experiences. Interviews were conducted in Lingala, and transcribed and translated into French for analysis. Deductive and inductive codes were applied, and matrices were created to facilitate cross-case analysis. Women had limited understanding of the specific mechanisms through which their infant feeding practices influenced HIV transmission risk. Clinical staff was the primary source of women's knowledge of HIV mother-to-child-transmission. Among the 24 post-partum women in the sample, seven women adhered to exclusive breastfeeding and two women to exclusive formula feeding for at least six months. Women's beliefs and awareness about HIV transmission through breastfeeding, as well as the information and support from clinical staff and other members of their support networks positively influenced their exclusive feeding. Common barriers to exclusive feeding included financial constraints, breast health problems, misinformation about HIV transmission, local norms, and prior feeding experiences. Health care workers play a key role in providing correct information on PMTCT and supporting women's infant feeding choices to adhere to guidelines of exclusive infant feeding. Optimizing provider-patient communication and creating a supportive environment surrounding infant feeding is critical.     

Advances and research directions in the prevention of mother-to-child HIV-1 transmission

Although substantial progress has been made in preventing mother-to-child HIV-1 transmission in the past decade, critical research questions remain. Two perinatal epidemics now exist. In more-developed countries, integration of prenatal HIV-1 counselling and testing programmes into an existing antenatal infrastructure, availability of effective antiretroviral prophylaxis, and access to infant formula have resulted in new perinatal infections becoming rare. However, identification of missed prevention opportunities, the causes of prophylaxis failure, and the potential effects of in-utero antiretroviral exposure have become a priority. In less-developed countries, antenatal care is limited, testing programmes are almost non-existent, effective interventions remain unimplemented, and prevention of postnatal transmission through breastmilk while maintaining adequate infant nutrition is a major dilemma. The challenge for the next decade is to simultaneously address questions relevant to both epidemics while bridging the gap in prevention of perinatal transmission between more-developed and less-developed countries.     

HIV infection in women: Do sex and gender matter?

At least half of all HIV infections occur in women. Most women are of childbearing potential; therefore, issues encompassing reproduction and mother-to-child transmission are critical in the management of this population. The efficacy of antiretroviral therapy (ART) is similar in men and women, although rates of adverse events or toxicity may be higher in women, which, in turn, may be related to higher antiretroviral drug levels documented in pharmacokinetic studies. A substantial proportion of women may not derive the benefit of highly active ART because nonsuppressive regimens are commonly used, especially in resource-limited settings, to decrease mother-to-child transmission. The likely emergence of resistant virus can have long-term sequelae for the mother, child, and other exposed individuals. Additional studies are needed of sex/gender-related issues including antiretroviral toxicities, pharmacokinetic profiles of approved and novel agents, ART strategies during pregnancy to minimize HIV resistance, and determination of optimal antiretroviral regimens for women.     

Decision analysis to guide choice of interventions to reduce mother-to-child transmission of HIV

INTRODUCTION: Antiretroviral prophylaxis, avoidance of breastfeeding, and early weaning are candidates to prevent mother-to-child transmission (MTCT) of HIV worldwide. METHODS: We developed a model to help guide population-level decisions about MTCT intervention strategies. We estimated the numbers of early childhood deaths prevented by (1) prenatal short-course zidovudine, (2) intrapartum and neonatal short-course nevirapine, (3) avoidance of breastfeeding, and (4) early weaning (age 6 months); four combinations of these; and one possible future strategy (postnatal antiretroviral prophylaxis) in a scenario typical of a developing country. We evaluated the effectiveness of the interventions for a range of R, the relative risk of mortality for children exposed to breastfeeding interventions compared with breastfed children (independent of HIV infection). We also estimated the reduction in breastfeeding transmission needed for a postnatal antiretroviral intervention to prevent more early childhood deaths than do currently available interventions. RESULTS: Where R < or = 1.5, strategies combining antiretroviral prophylaxis with breastfeeding interventions prevent the most early childhood deaths. However, strategies that include early weaning and avoidance of breastfeeding, respectively, can result in more deaths than with no intervention when R > 1.5 and R > 1.9, respectively. The relative effectiveness of a postnatal antiretroviral intervention compared with avoidance of breastfeeding varies with R; such that an intervention would be more effective than early weaning as a single intervention, at any R, if it reduced HIV transmission through breastfeeding by 25%. CONCLUSION: This spreadsheet model is a simple, locally adaptable tool to allow decision-makers to explore key questions about intervention strategies to prevent MTCT of HIV.     

Community approaches to preventing mother-to-child HIV transmission: perspectives from rural Lesotho

This paper examines the cultural and structural difficulties surrounding effective prevention of mother-to-child HIV transmission (PMTCT) in rural Lesotho. We argue for three strategies to improve PMTCT interventions: community-based research and outreach, addressing cultural and structural dynamics, and working with the relevant social groups that impact HIV prevention. These conclusions are based on interviews and participant observation conducted within the rural Mokhotlong district and capital city of Maseru, involving women and men of reproductive age, grandmothers serving as primary caretakers, HIV/AIDS programme staff, and medical professionals. Qualitative analysis focused on rural women's socio-medical experience with the four measures of PMTCT (educational outreach, voluntary counselling and testing, antiretroviral interventions, and safe infant feeding). Based on these results, we conclude that intervention models must move beyond a myopic biomedical 'best-practices' approach to address the social groups and contextual determinants impacting vertical HIV transmission. Given the complexities of effective PMTCT, our results show that it is necessary to consider the biomedical system, women and children, and the community as valuable partners in achieving positive health outcomes.     

Breastfeeding to prevent HIV transmission in infants: balancing pros and cons

PURPOSE OF REVIEW: In industrialized countries avoidance of breastfeeding is among the cornerstones of prevention of mother-to-child transmission of HIV. Breastfeeding carries risk for HIV transmission but improves survival, whereas formula feeding carries zero risk for transmission but increased risk for mortality. We assesses breastfeeding is a rational and viable option for HIV-infected women in poor environments. RECENT FINDINGS: A number of recent studies, mostly from Africa, have provided new data that enable health workers to offer HIV-positive women clear advice on infant feeding appropriate to their individual circumstances. The studies are grouped according to whether the evidence favours one or other feeding type and are considered under the following headings: equivalence of formula feeding and breastfeeding; breastfeeding, HIV disease progression and mortality in mothers; breast superior to formula; breastfeeding for HIV-infected babies; and reducing risk for transmission while breastfeeding. SUMMARY: The weight of current evidence favours exclusive breastfeeding for 6 months to prevent mother-to-child HIV transmission for most HIV-infected mothers globally, most of whom live in poor communities; exclusive breastfeeding may also benefit HIV-infected babies. Formula feeding appears to be equivalent to breastfeeding in terms of survival and transmission risk during the first 2 years of life in some settings.     

Infant feeding practices: realities and mind sets of mothers in Southern Africa

Exclusively breastfed infants in developing countries are at lower risk of HIV transmission than mixed-fed infants. Ethno-graphic research was conducted in eleven low-resource settings across South Africa, Namibia and Swaziland to understand how the perceptions and experiences of counselling health workers, pregnant women and recent mothers could be used to improve infant feeding counselling. Despite prevention of mother-to-child transmission (PMTCT) programmes, very early mixed-feeding remains the norm; traditional conceptualisations of 'water as life' and 'milk as a fluid' are holding up against current PMTCT education, with milk considered liquid 'drink' rather than 'real food'. This aggravates an 'insufficient milk syndrome' where disempowered mothers perceive their breastmilk, and themselves, as deficient - 'not good enough'. Infant feeding is embedded within traditional relationships of intimacy; both relatives and breadwinner have influence and even authority over options and modes of infant feeding. In patriarchal and violent societies, traditional power differentials prohibit easy or complete HIV disclosure or condom negotiation; HIV status remains hidden from most partners and relatives. This context of secrecy means that the traditional advice and authority, which the mothers feel they dare not disregard, is often blind to the mother and her infant's HIV status and survival needs.     

Physiology, immunology, and disease transmission in human breast milk

Breast feeding is an important mode of mother-to-child transmission of HIV. Interventions to decrease the number of infants becoming infected are particularly required for women in less developed countries where breast feeding is essential for infant survival. This review discusses the physiology and immunology of breast feeding and how maternal health interventions in the postpartum period may help decrease mother-to-child HIV transmission.     

170例HIV感染孕妇的妊娠结局分析

目的探讨并分析HIV感染孕妇的临床特征及妊娠结局。方法收集本院2007年1月—2018年11月期间HIV感染孕妇的流行病学资料,分析其流行病学特征以及妊娠结局。结果共纳入170例HIV感染孕妇,感染的主要方式为异性性传播。近3年诊治的HIV感染孕妇数量较前几年明显增多。孕妇的主要抗病毒方案为齐多夫定或替诺福韦+拉米夫定+洛匹那韦/利托那韦。婴儿主要抗病毒方案为齐多夫定或奈韦拉平。母婴阻断成功率100%。结论HIV感染孕妇数量呈上升趋势,及时对HIV感染孕妇进行规范系统的抗病毒治疗及对HIV暴露婴儿进行预防可有效阻断HIV母婴传播。     

Human immunodeficiency virus type 1 mother-to-child transmission and prevention: successes and controversies

The World Health Organization (WHO) and United Nations Programme on HIV/AIDS (UNAIDS) estimated that an additional 370 000 new human immunodeficiency virus type 1 (HIV-1) infections occurred in children in 2009, mainly through mother-to-child transmission (MTCT). Intrapartum transmission contributes to approximately 20-25% of infections, in utero transmission to 5-10% and postnatal transmission to an additional 10-15% of cases. MTCT accounts for only a few hundred infected newborns in those countries in which services are established for voluntary counselling and testing of pregnant women, and a supply of antiretroviral drugs is available throughout pregnancy with recommendations for elective Caesarean section and avoidance of breastfeeding. The single-dose nevirapine regimen has provided the momentum to initiate MTCT programmes in many resource-limited countries; however, regimens using a combination of antiretroviral drugs are needed also to effectively reduce transmission via breastfeeding.     

Forgotten but not gone: the continuing scourge of congenital syphilis

Much attention is being given to the prevention of HIV infection in babies through transmission from the mother. By contrast, regrettably little concern is raised about the increasing numbers of babies born with congenital syphilis. In affluent countries congenital syphilis is very rare, but in many poor countries, including the newly independent countries of eastern Europe and the former Soviet Union, the numbers are high and increasing. In much of sub-Saharan Africa, around 10% of pregnant women are affected by syphilis. The prevention of congenital syphilis is more cost-effective than the prevention of mother-to-child transmission of HIV. The control of congenital syphilis could indirectly have a beneficial effect on the HIV epidemic by reducing susceptibility to infection. Although the procedure to prevent congenital syphilis through antenatal screening and treatment is well established, implementation of effective programmes in resource-poor settings has proved very difficult. A new and focused approach to tackling congenital syphilis is needed. It should combine different mixes of interventions, such as mass treatment, focused screening, and universal screening, according to the local epidemiology and available resources. A task-force approach to defining the most appropriate interventions together with support for some research should be a priority for support under the Global Health Fund.     

A review of barriers and facilitators of HIV treatment among injection drug users

Globally, injection drug use continues to account for a substantial proportion of HIV infections. There have not, however, been any evidence-based reviews of the barriers and facilitators of HIV treatment among injection drug users. For this review, published studies were extracted from nine academic databases, with no language or date specified in the search criteria. Existing evidence demonstrates that, although injection drug users often have worse outcomes from HIV treatment than non-injection drug users, major antiretroviral-associated survival gains still have been observed among this population. Inferior outcomes are explained by a range of barriers to antiretroviral access and adherence, which often stem from the negative influences of illicit drug policies, as well as issues within medical systems, including lack of physician education about substance abuse. Evidence demonstrates that several under-utilized interventions and novel antiretroviral delivery modalities have helped to greatly address these barriers in several settings, and there is sufficient evidence to support immediate scale-up of these programmes. These interventions include coupling antiretroviral therapy with opioid substitution therapies as well as directly administered antiretroviral therapy programmes. Of particular interest for future evaluation is the coupling of HIV treatment programmes within comprehensive services, which also provide low-threshold (harm reduction) HIV prevention programmes. Scale-up of evidence-based HIV treatment and prevention to injection drug users, however, will require increasing political will among both national policy-makers and international public health agencies.