Articles tagged as "Preventing HIV infection in children"

December
13
2011

Maternal and child mortality

Progress towards Millennium Development Goals 4 and 5 on maternal and child mortality: an updated systematic analysis

Lozano R, Wang H, Foreman KJ, Rajaratnam JK, Naghavi M, Marcus JR, Dwyer-Lindgren L, Lofgren KT, Phillips D, Atkinson C, Lopez AD, Murray CJ. Lancet. 2011 Sep 24;378(9797):1139-65.

With 4 years until 2015, it is essential to monitor progress towards Millennium Development Goals (MDGs) 4 and 5. Although estimates of maternal and child mortality were published in 2010, an update of estimates is timely in view of additional data sources that have become available and new methods developed. The aim of Lozano and colleagues was to update previous estimates of maternal and child mortality using better data and more robust methods to provide the best available evidence for tracking progress on MDGs 4 and 5. They update the analyses of the progress towards MDGs 4 and 5 from 2010 with additional surveys, censuses, vital registration, and verbal autopsy data. For children, they estimate early neonatal (0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (ages 1-4 years), and under-5 mortality. They use an improved model for estimating mortality by age under 5 years. For maternal mortality, their updated analysis includes greater than 1000 additional site-years of data. They tested a large set of alternative models for maternal mortality; they used an ensemble model based on the models with the best out-of-sample predictive validity to generate new estimates from 1990 to 2011. Under-5 deaths have continued to decline, reaching 7.2 million in 2011 of which 2.2 million were early neonatal, 0.7 million late neonatal, 2.1 million postneonatal, and 2.2 million during childhood (ages 1-4 years). Comparing rates of decline from 1990 to 2000 with 2000 to 2011 shows that 106 countries have accelerated declines in the child mortality rate in the past decade. Maternal mortality has also continued to decline from 409,100 (uncertainty interval 382,900-437,900) in 1990 to 273,500 (256,300-291,700) deaths in 2011. They estimate that 56,100 maternal deaths in 2011 were HIV-related deaths during pregnancy. Based on recent trends in developing countries, 31 countries will achieve MDG 4, 13 countries MDG 5, and nine countries will achieve both. Even though progress on reducing maternal and child mortality in most countries is accelerating, most developing countries will take many years past 2015 to achieve the targets of the MDGs 4 and 5. Similarly, although there continues to be progress on maternal mortality the pace is slow, without any overall evidence of acceleration. Immediate concerted action is needed for a large number of countries to achieve MDG 4 and MDG 5.

For abstract access click here

Editor’s note: This article provides an update on the maternal mortality estimates provided by Hogan et al in HIV This Week Issue #81, along with progress on under-5 mortality. Although UNFPA has said ‘make each and every person count’, many countries have weak vital registration systems and health indicator tracking capacity. The ambitious targets of Millennium Development Goal 4 (reduce the under-5 mortality rate by two-thirds between 1990 and 2015) and Goal 5 (reduce the maternal-mortality ratio by three-quarters from 1990 and 2015) require measurement so that lessons can be learned from countries that are on track, resources can be mobilised, and adjustments can be made by countries that are lagging behind to spur the speed of their progress. The high-level Commission on Information and Accountability for Women’s and Children’s Health recommended that by 2015 ‘all countries have taken significant steps to establish a system for registration of births, deaths, and causes of death, and have well-functioning health information systems that combine data from facilities, administration services, and surveys’. In the interim, we have to rely on modelling-derived estimates that have varying degrees of uncertainty, depending on the strength of the available data to be entered into the models, among other factors. As well, there may be differences in what to track: HIV-associated maternal deaths or HIV-related maternal deaths. The Global Plan aims to achieve a 50% reduction in the number of HIV-associated deaths during pregnancy, delivery, and the puerperium by 2015. The UNAIDS Terminology Guidelines www.unaids.org/en/media/unaids/contentassets/documents/document/2011/20111025_UNAIDS_Terminology_Guidelines_En.pdf define HIV-associated deaths as deaths to women with HIV infection during pregnancy, delivery, or the puerperium, including direct maternal deaths to women who are HIV-positive, indirect maternal deaths aggravated by HIV, and HIV-related deaths to women during pregnancy, delivery, or puerperium. These authors define direct and indirect obstetric deaths as all maternal deaths minus the HIV-related deaths during pregnancy so the progress reported here may or may not mirror progress in the HIV-associated maternal mortality that the Global Plan Is tracking.

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December
13
2011

Early infant diagnosis

Early infant HIV-1 diagnosis programmes in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions

Ciaranello AL, Park JE, Ramirez-Avila L, Freedberg KA, Walensky RP, Leroy V. BMC Med. 2011 May 20;9:59.

Early infant diagnosis of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programmes providing prevention of mother-to-child transmission services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of early infant diagnosis programmes is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, Ciaranello and colleagues review challenges to uptake at each step in the early infant diagnosis cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. They next synthesize the available literature about the costs and cost effectiveness of early infant diagnosis programmes; identify areas for future research; and place these findings within the context of the benefits and challenges to early infant diagnosis implementation in resource-limited settings.

For abstract access click here 

Editor’s note: This excellent review summaries succinctly the challenges at each step of the early infant diagnosis cascade, from infant presentation for care, the offer of testing, parent/caregiver acceptance of testing, specimen processing, return of results to health care facilities, receipt of results by parents/caregivers, and linkage to care and treatment. WHO recommends that all children under 24 months of age who have proven HIV infection should be started on antiretroviral therapy – and studies have shown that the earlier the better. Diagnosis of true HIV infection, rather than detection of maternal antibodies, requires virological tests that can detect whether the virus itself is present or not. Infants of mothers not known to have HIV infection will be missed unless testing can be routinely offered to all infants in high prevalence settings. If that first test is an antibody test that comes up positive, then a virological test, such as a DNA PCR (polymerase chain reaction) test that gives qualitative yes/no results or a quantitative RNA PCR test, can diagnose actual HIV infection. Dried blood spot specimens¾blood obtained through heel stick and dried on filter paper¾are easily and cheaply transported because they are non-infectious and heat-stable. They work for the PCR tests and for p24 antigen tests that detect the viral capsid. But what is really needed is a point-of-care test that would cut the cascade losses due to loss of specimens, slow delivery of results, and unreliable timing for availability of results for parents/caregivers. Reports at the recent ICASA regional conference in Addis Ababa suggest that we will not have long to wait. In the meantime, if you want to understand these early infant diagnostic tests better, you can go to the WHO website to read: http://whqlibdoc.who.int/publications/2010/9789241599085_eng.pdf

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September
25
2011

Maternal health

WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modelling clinical outcomes in infants and mothers

Ciaranello AL, Perez F, Maruva M, Chu J, Engelsmann B, Keatinge J, Walensky RP, Mushavi A, Mugwagwa R, Dabis F, Freedberg KA; for the CEPAC-International Investigators. PLoS One. 2011;6(6):e20224. Epub 2011 Jun 2

The Zimbabwean national prevention of mother-to-child HIV transmission programme provided primarily single-dose nevirapine from 2002-2009 and is currently replacing single-dose nevirapine with more effective antiretroviral regimens. Published HIV and prevention of mother-to-child HIV transmission models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). Ciaranello and colleagues compared five prevention of mother-to-child HIV transmission regimens at a fixed level of prevention of mother-to-child HIV transmission medication uptake: 1) no antenatal antiretrovirals (comparator); 2) single-dose nevirapine; 3) WHO 2010 guidelines using "Option A" (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy for women with advanced disease); 4) WHO "Option B" (antiretroviral therapy during pregnancy/breastfeeding without advanced disease; lifelong antiretroviral therapy with advanced disease); and 5) "Option B+:" lifelong antiretroviral therapy for all pregnant/breastfeeding, HIV-infected women. Paediatric (4-6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected. Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal antiretrovirals) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of single-dose nevirapine (13.8 years) or Option B (13.9 years) compared to no antenatal antiretrovirals (14.0 years), Option A (14.0 years), or Option B+ (14.5 years). Replacement of single-dose nevirapine with currently recommended regimens for prevention of mother-to-child HIV transmission (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both paediatric and maternal outcomes.

For abstract access click here

Editor’s note: The results of these computer simulation models applied in the Zimbabwe context are likely applicable to other settings in sub-Saharan Africa where prolonged breastfeeding is common. The largest improvements in both paediatric and maternal outcomes result from offering lifelong antiretroviral therapy to all pregnant women with HIV infection regardless of CD4 count (Option B+). As countries move away from single dose nevirapine, they need to consider the potential adverse effects of antiretroviral therapy discontinuation in Options A and B, such as marked increases in viral load, inflammatory markers, and risk for both AIDS and non-AIDS-related events. But should they choose these options, the most important influence on maternal life expectancy is Prong 4 linkage to post-natal maternal HIV care so that antiretroviral therapy is initiated in a timely fashion. This will reduce the costly morbidity and mortality associated with delayed maternal antiretroviral therapy initiation.

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August
28
2011

Breastfeeding

Acceptability of donated breast milk in a resource limited South African setting

Coutsoudis I, Petrites A, Coutsoudis A. Int Breastfeed J. 2011;6:3.

The importance of breast milk for infants' growth, development and overall health is widely recognized. In situations where women are not able to provide their infants with sufficient amounts of their own breast milk, donor breast milk is the next preferred option. Although there is considerable research on the safety and scientific aspects of donor milk, and the motivations and experiences of donors, there is limited research addressing the attitudes and experiences of the women and families whose infants receive this milk. This study therefore examined attitudes towards donated breast milk among mothers, families and healthcare providers of potential recipient infants. The study was conducted at a public hospital and nearby clinic in Durban, South Africa. The qualitative data was derived from eight focus group discussions which included four groups with mothers; one with male partners; and one with grandmothers, investigating attitudes towards receiving donated breast milk for infants. There was also one group each with nurses and doctors about their attitudes towards donated breast milk and its use in the hospital. The focus groups were conducted in September and October 2009 and each group had between four and eleven participants, leading to a total of 48 participants. Although breast milk was seen as important to child health there were concerns about undermining of breast milk because of concerns about HIV and marketing and promotion of formula milks. In addition there were concerns about the safety of donor breast milk and discomfort about using another mother's milk. Participants believed that education on the importance of breast milk and transparency on the processes involved in sourcing and preparing donor milk would improve the acceptability. This study has shown that there are obstacles to the acceptability of donor milk, mainly stemming from lack of awareness/familiarity with the processes around donor breast milk and that these could be readily addressed through education. Even the more psychological concerns would also likely be reduced over time as these educational efforts progress. With government and health care worker endorsement and commitment, breast milk donation could have a promising role in improving child health.

For abstract access click here

Editor’s note: WHO recommends donated breast milk as the next preferred option for infants who cannot receive breast milk from their own mothers. Donor breast milk is superior to formula, retaining much of its nutritional and immunological properties, particularly when the age of the donor’s own infant can be matched to that of the recipient infant. Although donor breast milk banks have been safely set up in resource-limited settings, they may be underutilised because of both provider attitudes and mother/partner/family concerns. Where once-common wet nursing—breastfeeding someone else’s infant—has been abandoned due to HIV, there may be deep-seated fears and suspicions about the safety of donor milk. Discomfort with the idea of using a bodily fluid from another person and fear of HIV transmission to the infant combine with basic lack of knowledge about donor screening processes and milk pasteurisation (which kills HIV). This study suggests that learning about breast milk donation should be part of antenatal education, emphasising that inability to produce breast milk is a medical circumstance not a personal shortcoming. Broader campaigns to promote breastfeeding should incorporate the concept of donor milk In order to raise awareness and create positive attitudes towards provision and use of donor milk. Mothers living with HIV are recommended to breastfeed exclusively for the first 6 months of their baby’s life. Donor breast milk can help them maintain exclusive breastfeeding when they are temporarily unable to breastfeed.

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May
15
2011

Paediatric HIV infection

Clinical manifestations and outcome in HIV-infected young infants presenting with acute illness in Durban, South Africa

Jeena PM, Reichert K, Adhikari M, Popat M, Carlin JB, Weber MW, Hamer DH. Ann Trop Paediatr. 2011;31(1):15-26

In young infants, early development of symptomatic HIV infection increases the risk of morbidity and mortality. A prospective study was conducted over a 1-year period in a region with a high burden of HIV in order to describe the clinical presentation of HIV infection in infants aged between 0 and 59 days on attendance at hospital and the factors associated with the need for urgent hospital management. Sick young infants presenting to the King Edward VIII Hospital, Durban between February 2003 and January 2004 were enrolled. After systematic evaluation by a primary health worker, an experienced paediatrician determined the primary diagnosis and need for urgent hospital management. Comparisons of these assessments were stratified by HIV status. Children were classified as HIV-uninfected (HIV ELISA-negative), HIV-exposed-but-uninfected (HIV ELISA-positive and HIV RNA PCR-negative), HIV-infected (HIV ELISA-positive and HIV viral load >400 copies/ml). Of 925 infants enrolled, 652 (70·5%) had their HIV status determined: 70 (10·7%) were HIV-infected, 271 (41·6%) HIV-exposed-but-uninfected, and 311 (47·7%) HIV-uninfected. Factors associated with an increased probability of being HIV-infected included if the mother had children from more than one sexual partner, if the infant had had contact with a tuberculosis-infected person or if the HIV-infected mother and/or her exposed infant failed to receive nevirapine prophylaxis. Signs of severe illness were more frequently encountered in HIV-infected than in HIV-exposed-but-uninfected infants, including the prevalence of chest in-drawing (20·3% vs 8·8%, p = 0·004) and severe skin pustules (18·6% vs 8·6%, p = 0·01). Among infants requiring urgent hospital management, observed or reported feeding difficulties and severe skin pustules were more common in HIV-infected than uninfected infants. More HIV-infected infants (12·9%) required hospitalisation than those who were HIV-exposed-but-uninfected (7·7%) or uninfected (7·4%). Primary diagnoses of pneumonia, sepsis or oral thrush were more frequently seen in HIV-infected than exposed-but-uninfected or HIV-uninfected children. Early recognition and triaging of infants suspected of having HIV infection provides an opportunity for early diagnosis and treatment which could prevent the adverse impact of rapidly progressive HIV disease.

For abstract access click here

Editor’s note: Although the presentation of common clinical illnesses in infancy has been altered by the HIV epidemic, relatively little has been published on how to recognise HIV infection in infants aged 0 to 59 days of age. Doing so is critical to prevent rapidly progressive HIV disease and infant mortality. This study in Durban describes a clinical presentation of HIV infection in young infants of oral thrush, chronic diarrhoea, chest in-drawing and/or severe skin pustules, with the likelihood of HIV infection increased if the mother has children from more than one sexual partner or if the infant has had contact with a person infected by tuberculosis. This description may help primary health care workers effectively triage patients. Once HIV infection is suspected, a p24 antigen assay or PCR test (polymerase chain reaction) can be offered to rapidly confirm the presence of HIV so that antiretroviral therapy and cotrimoxasole can be immediately initiated. The clinical presentation described here provides information that can help health care workers in HIV-endemic settings to appropriately identify and manage these infants, but the clinical presentation of HIV disease in young infants is likely to vary somewhat by setting.

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March
27
2011

HIV and maternal mortality

Strengthening HIV services for pregnant women: an opportunity to reduce maternal mortality rates in Southern Africa/sub-Saharan Africa

Moodley J, Pattinson RC, Baxter C, Sibeko S, Abdool Karim Q. BJOG. 2011 Jan;118(2):219-25

Reliable data from South Africa emanating from WHO recommendations for the Safe Motherhood programme underscore HIV-related illness as the most common cause of maternal deaths. The strengthening of HIV services for pregnant women, especially in countries with a high burden of HIV infection, will reduce HIV-related and un-related maternal mortality rates. High-quality and complete data on maternal deaths is a critical foundation for reliably monitoring temporal trends in maternal deaths, and causes thereof, but needs substantial strengthening in many resource-constrained settings. HIV is an increasing contributor to direct and indirect causes of maternal deaths in sub-Saharan Africa. A review of published data on maternal deaths and its association with HIV shows that reliable data come from the Confidential Enquiries into Maternal Deaths from South Africa, population-based surveys in sentinel populations, and facility-based data. Despite an increase in knowledge of the HIV status of pregnant women and the initiation of antiretroviral treatment, reversals in trends towards increased maternal deaths are not being observed. The strengthening of HIV services provides an opportunity to alter HIV epidemic trajectories and reduce maternal deaths.

Abstract

Editors’ note: The figures are stark: each year 80 million women have unwanted pregnancies and a third of maternal deaths could be prevented through the promotion and uptake of family planning. Each year there are more than 2 million pregnancies in women living with HIV and, in resource-constrained settings, HIV accounts for an estimated ten-fold increased risk of maternal death. This is not because pregnancy increases HIV disease progression—it does not do so in asymptomatic women—but rather because symptomatic women with HIV infection are at greater risk of dying from infectious diseases. Maternal mortality is defined as a death during pregnancy or within 42 days of the end of pregnancy from any cause related to or aggravated by pregnancy or its management, not including accidental or incidental causes. Maternal deaths are underestimated because not all women use health care facilities during pregnancy, for delivery, or for post-pregnancy care – and facility-based reports are the prime source of maternal mortality data. The action agenda is clear. To get Millennium Development Goal 5 on track by reducing the contribution of AIDS to maternal mortality, we must prevent HIV infection in women and girls, prevent unwanted pregnancies, expand HIV testing and counselling, accelerate initiation of antiretroviral treatment in pregnant women who are HIV-positive, and strengthen service delivery and integration of HIV care and obstetric services, along with data collection to track progress.

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March
27
2011

Discordant couples

Pregnancy and HIV transmission among HIV-discordant couples in a clinical trial in Kisumu, Kenya

Brubaker S, Bukusi EA, Odoyo J, Achando J, Okumu A, Cohen CR. HIV Med. 2010 Oct 14. doi: 10.1111/j.1468-1293.2010.00884.x

A large proportion of new HIV infections in sub-Saharan Africa occur in stable HIV-discordant partnerships. In some couples, the strong desire to conceive a child may lead to risky behaviour despite knowledge of discordant serostatus. Brubaker and colleagues’ objective was to compare HIV transmission between discordant couples who did and did not conceive during participation in a clinical trial. Five hundred and thirty-two HIV-discordant couples were followed for up to 2 years in Kisumu, Kenya as part of the Partners in Prevention HSV/HIV Transmission Study. Quarterly HIV-1 antibody and urine pregnancy test results were analysed. Forty-one HIV-1 seroconversions occurred over 888 person-years of follow-up, resulting in an annual incidence of 4.6/100 person-years. Twenty seroconversions occurred among 186 HIV-1-uninfected individuals in partnerships in which pregnancy occurred (10.8% of HIV-1-negative partners in this group seroconverted), in comparison to 21 seroconversions among 353 uninfected individuals in partnerships in which pregnancy did not occur (5.9% of HIV-1-negative partners seroconverted), resulting in a relative risk of 1.8 [95% confidence interval 1.01-3.26; P<0.05]. Pregnancy was associated with an increased risk of HIV seroconversion in discordant couples. These data suggest that the intention to conceive among HIV discordant couples may be contributing to the epidemic.

Abstract

Editors’ note: This study did not collect information about intention to conceive so it is actually not possible to know whether the pregnancies that occurred are a marker of unprotected intercourse rather than intention to conceive. Women enrolled in this study had verbally agreed to delay pregnancy until the end of the trial and were provided access to condoms and hormonal contraception free of charge. Despite this, 35% of them became pregnant, with no significant difference in the pregnancy rate between those who had HIV infection and those who did not. In the 20 couples in which both pregnancy and HIV seroconversion occurred, 12 women and 8 men became infected. Why HIV transmission was more likely to occur in couples who became pregnant is unclear. No genetic fingerprinting is reported to allow linkage between the index person’s virus and that of the couple member who seroconverted. If the transmissions are all linked, does pregnancy somehow increase susceptibility or transmissibility? In any case, this study underscores the importance of a harm reduction approach to counselling about reproductive choice which includes counselling about timed unprotected intercourse, home insemination, or confirmation of viral suppression.

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March
27
2011

Preventing vertical transmission

Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study

Humphrey JH, Marinda E, Mutasa K, Moulton LH, Iliff PJ, Ntozini R, Chidawanyika H, Nathoo KJ, Tavengwa N, Jenkins A, Piwoz EG, Van de Perre P, Ward BJ; ZVITAMBO study group. BMJ. 2010 Dec 22;341:c6580

Humphrey and colleagues estimated the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery. This prospective cohort study that enrolled 14 110 women and infants in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001) also assessed postnatal mother to child transmission of HIV and collected information on breast milk and maternal plasma HIV load during the postpartum period. Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breastfeeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally. Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests.

Abstract

Editors’ note: The ZVITAMBO trial is the largest vertical HIV transmission trial ever reported and although it found that Vitamin A supplements did not prevent mother-to-child transmission, it is a rich source of data. This study found that 8.5% of infants born without HIV to chronically HIV-infected women became infected through breastfeeding during the first year of life, a risk that was constant over time. Infants of women who were HIV-negative at delivery and subsequently seroconverted while breastfeeding had a 23.6% risk of acquiring HIV by 12 months. Just as in sexual transmission, very high rates of transmission were seen during the acute infection period, with the transmission rate among postnatal seroconverter women 8 times the transmission risk of chronically infected women. During the first 30 days of acute infection, the median breast milk viral load peaked in the same range as plasma viral load. What conclusion can we draw? The WHO infant feeding guidelines on maternal antiretroviral prophylaxis or therapy while breastfeeding and infant prophylaxis will not address this problem because these women would not be offered this strategy – they seroconverted after delivery. Even monthly HIV antibody testing following delivery would not identify women in the acute infection period when they are most likely to transmit. Only preventing HIV acquisition in women—primary prevention—will address this. This is a cogent argument for including breastfeeding women in high HIV prevalence areas in topical and oral pre-exposure prophylaxis trials. In the meantime, it is important to spread the word that pregnancy and breastfeeding are times of increased risk of HIV acquisition for women and that correct and consistent condom use by men who have sex with them will protect their infants and reduce the risk that they may become eventual maternal orphans.

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February
21
2011

Preventing mother-to-child (vertical) transmission

Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial

The Kesho Bora Study Group – Lancet on line Jan 14

 

Breastfeeding is essential for child health and development in low-resource settings but carries a significant risk of transmission of HIV-1, especially in late stages of maternal disease. The Kesho Bora Study Group aimed to assess the efficacy and safety of triple antiretroviral prophylaxis compared with zidovudine and single-dose nevirapine prophylaxis in pregnant women infected with HIV. Pregnant women with WHO stage 1, 2, or 3 HIV-1 infection who had CD4 cell counts of 200-500 cells per μL were enrolled at five study sites in Burkina Faso, Kenya, and South Africa to start study treatment at 28-36 weeks' gestation. Women were randomly assigned (1:1) by a computer generated random sequence to either triple antiretroviral prophylaxis (a combination of 300 mg zidovudine, 150 mg lamivudine, and 400 mg lopinavir plus 100 mg ritonavir twice daily until cessation of breastfeeding to a maximum of 6·5 months post partum) or zidovudine and single-dose nevirapine (300 mg zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labour and, after a protocol amendment in December, 2006, 1 week post-partum zidovudine 300 mg twice daily and lamivudine 150 mg twice daily). All infants received a 0·6 mL dose of nevirapine at birth and, from December, 2006, 4 mg/kg twice daily of zidovudine for 1 week after birth. Patients and investigators were not masked to treatment. The primary endpoints were HIV-free infant survival at 6 weeks and 12 months; HIV-free survival at 12 months in infants who were ever breastfed; AIDS-free survival in mothers at 18 months; and serious adverse events in mothers and babies. Analysis was by intention to treat. From June, 2005, to August, 2008, 882 women were enrolled, 824 of whom were randomised and gave birth to 805 singleton or first, liveborn infants. The cumulative rate of HIV transmission at 6 weeks was 3·3% (95% CI 1·9-5·6%) in the triple antiretroviral group compared with 5·0% (3·3-7·7%) in the zidovudine and single-dose nevirapine group, and at 12 months was 5·4% (3·6-8·1%) in the triple antiretroviral group compared with 9·5% (7·0-12·9%) in the zidovudine and single-dose nevirapine group (p=0·029). The cumulative rate of HIV transmission or death at 12 months was 10·2% (95% CI 7·6-13·6%) in the triple antiretroviral group compared with 16·0% (12·7-20·0%) in the zidovudine and single-dose nevirapine group (p=0·017). In infants whose mothers declared they intended to breastfeed, the cumulative rate of HIV transmission at 12 months was 5·6% (95% CI 3·4-8·9%) in the triple antiretroviral group compared with 10·7% (7·6-14·8%) in the zidovudine and single-dose nevirapine group (p=0·02). AIDS-free survival in mothers at 18 months will be reported in a different publication. The incidence of laboratory and clinical serious adverse events in both mothers and their babies was similar between groups. Triple antiretroviral prophylaxis during pregnancy and breastfeeding is safe and reduces the risk of HIV transmission to infants. Revised WHO guidelines now recommend antiretroviral prophylaxis (either to the mother or to the baby) during breastfeeding if the mother is not already receiving antiretroviral treatment for her own health.

Abstract:

Editors’ note: Kesho Bora means ‘a better future’ in Swahili and this trial proved that triple antiretroviral prophylaxis to mothers with HIV infection offers exactly that to their breastfeeding infants. The Kesho Bora trial recruited women with CD4 counts higher than the 200 cells/µl required for treatment at the time to be randomised to either the standard of care of zidovudine (AZT) prophylaxis during pregnancy and single dose-nevirapine during delivery, or to triple antiretroviral prophylaxis. The result was 43% fewer infections at 12 months of age in infants whose mothers received the triple drug prophylaxis. Transmission rates at birth and at 6 weeks were not significantly different between the two groups. In both groups, 78% of infants were ever breastfed – the triple antiretroviral prophylaxis regimen during breastfeeding cut the risk of HIV transmission in half. These findings influenced the 2010 WHO recommendations to provide antiretroviral prophylaxis for the mother or the baby during breastfeeding. As for prophylaxis during pregnancy, there are two choices now for women with CD4 counts over 350 cells/µl who are not yet eligible for antiretroviral treatment for their own health. The first is to take AZT from as early as 14 weeks of pregnancy, add a single dose of nevirapine at the onset of labour, and follow with AZT/3TC during labour and delivery and for 7 days after delivery, with breastfeeding infants receiving nevirapine until 1 week after breastfeeding ends. The second is simpler: women take one of several triple antiretroviral prophylaxis regimens from 14 weeks of pregnancy until 1 week after breastfeeding ends, with infants receiving nevirapine until 6 weeks of age. Breastfeeding provides optimal nutrition and protects against pneumonia and diarrhoea – now antiretroviral drugs make it safer for babies exposed to HIV.

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January
29
2011

Preventing mother-to-child (vertical) transmission

What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs

Mahy M, Stover J, Kiragu K, Hayashi C, Akwara P, Luo C, Stanecki K, Ekpini R, Shaffer N. Sex Transm Infect. 2010 Dec;86 Suppl 2:ii48-55

The number of HIV-positive pregnant women receiving antiretroviral drugs to prevent mother-to-child transmission of HIV has increased rapidly. The objectives of this study were to estimate the reduction in new child HIV infections resulting from prevention of mother-to-child transmission over the past decade, to project the potential impact of implementing the new WHO PMTCT guidelines between 2010 and 2015, and to consider the efforts required to virtually eliminate mother-to-child transmission, defined as <5% transmission of HIV from mother to child, or 90% reduction of infections among young children by 2015. Data from 25 countries with the largest numbers of HIV-positive pregnant women were used to create five scenarios to evaluate different prevention of mother-to-child transmission interventions. A demographic model, Spectrum, was used to estimate new child HIV infections as a measure of the impact of interventions. Between 2000 and 2009 there was a 24% reduction in the estimated annual number of new child infections in the 25 countries, of which about one-third occurred in 2009 alone. If these countries implement the new WHO prevention of mother-to-child transmission recommendations between 2010 and 2015, and provide more effective antiretroviral prophylaxis or treatment to 90% of HIV-positive pregnant women, 1 million new child infections could be averted by 2015. Reducing HIV incidence in reproductive age women, eliminating the current unmet need for family planning and limiting the duration of breastfeeding to 12 months (with antiretroviral prophylaxis) could avert an additional 264 000 infections, resulting in a total reduction of 79% of annual new child infections between 2009 and 2015, approaching but still missing the goal of virtual elimination of mother-to-child transmission. To achieve virtual elimination of new child infections prevention of mother-to-child transmission programmes must achieve high coverage of more effective antiretroviral interventions and safer infant feeding practices. In addition, a comprehensive approach including meeting unmet family planning needs and reducing new HIV infections among reproductive age women will be required.

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Editors’ note: The 25 high-burden countries included in this analysis of what it will take to meet the targets to virtually eliminate vertical HIV transmission account for 91% of HIV-positive pregnant women in lower- and middle-income countries. The most striking finding of this modelling of five possible scenarios is that an exclusive focus on ensuring that 90% of pregnant women are either on antiretroviral treatment or on highly active antiretroviral prophylaxis from 14 weeks of pregnancy through breastfeeding (known as Prong 3 of the strategy) will not get us there – it would reduce the number of new child infections by 60%, well short of the 90% by 2015 target. Halving HIV incidence in women (Prong 1) and reducing unmet need for family planning (Prong 2), neither of which would affect HIV transmission rate (the goal is less than 5% by 2015), would reduce new child infections further (to 73%). Adding the effects of restricting breastfeeding under antiretroviral cover of mother or infant to 12 months achieves a 79% reduction. Each of the 25 countries has its own situation to address, whether high HIV incidence in Lesotho, unmet need for family planning in Uganda, poor antenatal service coverage in Ethiopia, or prolonged breastfeeding in many countries. However, this modelling demonstrates that countries are more likely to reach virtual elimination if they create demand for and provide contraceptive services to prevent unplanned pregnancy.

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