PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Curr Opin HIV AIDS. Author manuscript; available in PMC 2011 January 1.
Published in final edited form as:
PMCID: PMC2927492
NIHMSID: NIHMS227778

Use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income countries

Abstract

Purpose of review

The purpose of the study was to review recent evidence on the use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income settings.

Recent findings

Access to antiretroviral prophylaxis strategies for HIV-infected pregnant women has increased globally, but two-thirds of women in need still do not receive even the simplest regimen for the prevention of mother-to-child transmission of HIV, and most pregnant women in need of antiretroviral treatment do not receive it. The use of combination antiretroviral treatment in pregnancy in low-resource settings is safe and effective, and increasing evidence supports starting ongoing antiretroviral treatment at a CD4 cell count below 350/μl in pregnant women. The use of appropriate short-course antiretroviral prophylactic regimens is effective for prevention of mother-to-child transmission of HIV in women with higher CD4 cell counts. New data on the use of antiretroviral prophylaxis to prevent transmission through breastfeeding demonstrate that both maternal antiretroviral treatment and extended infant prophylaxis are effective.

Summary

Antiretroviral use in pregnancy can benefit mothers in need of treatment and reduce the risk of mother-to-child transmission. Emerging evidence of the effectiveness of antiretroviral prophylaxis in preventing transmission through breastfeeding is encouraging and likely to influence practice in the future.

Keywords: antiretroviral drugs, breastfeeding, HIV, pregnancy, prevention of mother-to-child transmission

Introduction

Mother-to-child transmission of HIV (MTCT) has become a rare event in well resourced settings, with the widespread access to effective antiretroviral treatment, but around 370 000 children were newly infected with HIV in 2008, with 90% of these in sub-Saharan Africa [1••]. This represents a decrease from previous estimates [2], which may reflect the growing impact of prevention of mother-to-child transmission (PMTCT) programs. The complications of HIV infection are also major causal factors for maternal mortality in high prevalence HIV areas, especially in sub-Saharan Africa [3,4•,5,6], and it appears that increased antiretroviral treatment access has yet to result in an improvement in maternal mortality figures in high prevalence settings [7•].

Antiretroviral access

Access to antiretroviral therapy has expanded dramatically in low-resource settings in the past 3 years, rising by 42% in 2007 alone, providing treatment to more than 3 million people, but still not reaching the other two-thirds of the estimated 9.7 million people in need of treatment [1••,8••,9]. This increased access to treatment has resulted in more widespread use in pregnant women, but coverage of antiretrovirals, either as treatment or for prophylaxis remains low, despite some very successful initiatives [10•,11,12•,13]. The global coverage of PMTCT services remains suboptimal with only 18% of all pregnant women in low-income and middle-income countries (20.6 million of 115 million pregnant women) estimated to have received an HIV test in 2007, though this had increased from estimates of 16% in 2006 and 10% in 2005 [8••]. Only 33% of HIV-infected women are estimated to have received some PMTCT intervention in 2008, up from 10% previously. HIV testing is essential to identify HIV-infected women in need of antiretroviral interventions, and provider-initiated testing has been shown to dramatically increase uptake rates and facilitate access to care [1416]. In this review, recent data on aspects of the use of antiretrovirals in pregnant women and during the breastfeeding period for maternal health and for PMTCT are discussed.

Antiretroviral use during pregnancy

The role of the use of combination highly active antiretroviral therapy (HAART) both to benefit maternal health and to reduce the risk of transmission to infants is well established and acknowledged in all major international guidelines [17,18••,19••]. The availability of HAART has driven the transmission rates of HIV to below 1–2% in well resourced settings and has dramatically reduced the numbers of new cases of HIV infection in children to an estimate of less than 500 annually across the whole of the United States and Europe combined [1••]. As an example of this success, in the United Kingdom and Ireland between 2000 and 2006, the overall MTCT rate was 1.2%, and it was 0.8% for women who received at least 14 days of antiretroviral therapy [20]. Similarly, low transmission rates are reported in most well resourced countries [2124], but progress in low-resource settings has not been as dramatic.

Combination antiretroviral treatment

The WHO reports that only around 12% of HIV-infected pregnant women were assessed for their eligibility to receive antiretroviral therapy in 2007, either clinically or immunologically by CD4 cell count, demonstrating the need for urgent action to improve these services [8••]. Where HAART is available in low-resource settings, the use in pregnancy, either for ongoing treatment or as prophylaxis, has been reported to be safe and effective, in line with experience in well resourced countries, though reports of increased rates of prematurity suggest the need for further investigation of this aspect [12•,2527,28•,29•,30,31•].

Short-course antiretroviral prophylaxis for prevention of mother-to-child transmission

The use of even the most simple, single-dose nevirapine (NVP)-based PMTCT regimens has been estimated to have averted over 30 000 infections in infants in 2004 and 2005, and this figure is likely to be considerably higher with the increased access to antiretrovirals over the past 5 years [32]. The WHO guidelines for PMTCT, issued in 2006, provide a consensus approach to antiretroviral use in pregnancy for low-resource settings, which includes the provision of HAART for pregnant women who require ongoing treatment, provision of an appropriate antiretroviral prophylactic regimen for those who do not yet need treatment and appropriate adaptation of infant feeding practices [17]. Substantial data from low-resource countries have shown the efficacy of short-course antiretroviral regimens in these settings [33,34••,35,36•,37•,38]. The use of HAART regimens for prophylaxis is likely to increase in these settings as general access to antiretroviral treatment improves. Concerns remain around the development of NVP resistance in mothers and infants following the use of NVP in PMTCT short-course regimens, or as extended prophylaxis to infants, and the potential impact of this on maternal and infant treatment options [3943,44••,45].

Antiretroviral prophylaxis during breastfeeding

In well resourced settings, the complete avoidance of breastfeeding has been a major factor in reducing transmission, and breastfeeding is not recommended for HIV-infected women (including those receiving HAART) [18••,19••]. Although the use of replacement feeding has been documented to be safe and feasible in some less resourced settings, such as in Thailand, Brazil and some African urban areas, it is not a feasible option in many low-resource settings [37•,46,47•,48]. The use of exclusive breastfeeding rather than ‘mixed’ feeding has been shown to provide some protection against infection, but this does not prevent all infections, with transmission rates in exclusively breastfed infants of up to 14% at 6 weeks and 20% at 6 months even in the best managed research settings [49]. Exclusive breastfeeding is not easy to achieve, and its successful promotion relies also on providing supportive health services and in having willing mothers [47•,50••,51,52]. The WHO infant feeding guidance from 2006 reinforced the recommendation that avoidance of breastfeeding should only be recommended for HIV-infected women if affordable, feasible, acceptable, safe and sustainable (AFASS) and recommended weaning as soon as possible to reduce the ongoing risk of infections [53]. An increasing body of evidence since then from very low-resource settings has demonstrated that early weaning may reduce HIV transmission risk but is balanced by a much higher rate of morbidity and mortality in the infants [54••,5557], and that inappropriate replacement feeding use may have similar consequences [58]. These effects appear to be more severe in infants born to mothers with more advanced disease and lower CD4 cell counts, adding to the urgency to provide appropriate antiretroviral treatment for these mothers [59,60]. The need to find alternative strategies that could maintain the benefits of breastfeeding while reducing the risks of HIV transmission has led to research in two areas of antiretroviral prophylaxis through the period of breastfeeding: either the provision of HAART to mothers or extended prophylaxis to breastfed infants.

Maternal highly active antiretroviral therapy through breastfeeding

Several observational trials have reported success in reducing breast milk transmission in women receiving HAART through the period of breastfeeding [61•,62]. In the Mitra plus study, a transmission rate of 0.9% at 6 months was achieved in infants of women given a HAART regimen of zidovudine (AZT), lamivudine (3TC) and NVP, rising to 1.7% at 12 months and 1.9% at 18 months [62,63]. The Allaitement MAternal sous Tritherapie Antiretrovirale (AMATA) study, conducted in Rwanda, has also reported success of this strategy, with no transmission in women on HAART at 7 months of follow-up [64]. In Mozambique, the Drug Resource Enhancement against AIDS and Malnutrition (DREAM) program has reported a 12-month transmission rate of 1.3% through breastfeeding in infants of mothers on HAART [26] and a positive effect on infant HIV-free survival of infants at 1 year of age as a result of HAART to mothers [25]. In Kenya, the Kisumu Breastfeeding study (KIBS) [65] gave HAART (AZT and 3TC with either NVP or nelfinavir, depending on maternal CD4 cell count) and showed transmission rates of 1.5% at 6 weeks, 2.6% at 6 months and 3.5% at 12 months.

Data from two randomized trials were presented at the 5th IAS Conference, Cape Town, South Africa, 19–22 July 2009, which add important information for this field.

The Kesho Bora study [66], conducted at sites in Burkina Faso, Kenya and South Africa, randomized pregnant women with CD4 cell counts between 200 and 500 cells/μl, between 28 and 36 weeks of pregnancy, to receive either short-course AZT and single-dose NVP in labor or to maternal HAART [AZT, 3TC and lopinavir/ritonavir (LPV/r)]. Treatment was continued in the HAART group to approximately 6.5 months after delivery (or until breastfeeding cessation if this occurred earlier). All infants received single-dose NVP postpartum, and 1-week maternal ‘tail’ coverage was added to the short-course regimen and 1-week AZT for all infants, as guidelines changed during the study. The cumulative infection rate for infants whose mothers had a baseline CD4 cell count 200–350 cells/μl was significantly reduced at 5.5 vs. 10.5% at 6 months and 6.1 vs. 11.1% at 12 months in the HAART and short-course arms. However, for infants of mothers with baseline CD4 cell counts between 350 and 500 cells/μl, the rates were 4.1 vs. 5.9% at 6 months and 4.9 vs. 7.4% at 12 months, which were not significantly different (P= 0.33). The largest effects were seen between 6 weeks and 6 months [66]. These results add further weight to recommendations to start ongoing antiretroviral therapy at a CD4 cell level of 350 cells/μl or less, and as in the observational studies, provide more evidence of an effect of maternal HAART in reducing breast milk transmission compared with the current standard antepartum and intrapartum short-course regimen.

The Mma Bana study [67] is the first randomized controlled trial to compare two antiretroviral regimens in pregnancy and during breastfeeding. It was a randomized controlled trial in Botswana comparing two HAART regimens given to pregnant and breastfeeding mothers, starting between 26 and 34 weeks of pregnancy and continued until breastfeeding cessation at 6 months postpartum. Women in the trial had CD4 cell counts above 200 cells/μl and would otherwise not eligible for antiretroviral treatment according to the local guidelines. The two regimens compared were abacavir (ABC), AZT and 3TC coformulated as Trizivir, or LPV/r, AZT and 3TC given as Kaletra and Combivir. The study demonstrated excellent adherence to the treatment regimens (over 90%), with a median of 11-week antepartum treatment, high adherence to exclusive breastfeeding (93%) and to cessation of breastfeeding at 6 months, with very low loss to follow-up. The overall transmission rate in this study at 6 months was 1% [95% confidence interval (CI) 0.5–2.0] with only 0.3% of infections occurring during the 6-month period of breastfeeding. Maternal virologic suppression rates at delivery and during breastfeeding did not differ by HAART regimen. This study demonstrates excellent effectiveness of a HAART strategy through pregnancy and breastfeeding in achieving a major reduction in transmission rates.

Extended infant antiretroviral prophylaxis

Two published reports have demonstrated the effect of extended NVP prophylaxis to breastfed infants. In the Six-Week Extended Nevirapine (SWEN) study [68••], a set of comparable trials conducted in Ethiopia, India and Uganda, there was a significant difference in HIV transmission rates at 6weeks between HIV-exposed infants who received a single postpartum dose of NVP and those who received an extended regimen of daily NVP for 6 weeks, with a relative risk of 0.54 (95% CI 0.34–0.85). However, at 6 months, the difference was not significant. An extended 14-week course of NVP, with or without added AZT, commenced at birth in HIV-exposed infants decreased the risk of HIV transmission by as much as 50% at 9 months compared with the standard regimen of single-dose NVP and 1 week of AZT in the Post-Exposure Prophylaxis of Infant (PEPI) study in Malawi [69••]. There appeared to be no added protection afforded by the addition of extended AZT in addition to the NVP. This benefit was lost by 12 months when breastfeeding was prolonged. The results of these two trials suggest that transmission is not reduced after the extended NVP is stopped, and that more prolonged administration, at least to 6 months, to cover the period of exclusive breastfeeding could be needed.

Other studies on infant prophylaxis, including the Mitra and Stopping Infection from Mother-to-child via Breast-feeding in Africa (SIMBA) studies, have also shown efficacy of extended antiretroviral regimens in decreasing the risk of breast milk transmission, but the duration of breastfeeding was short and the rate of exclusive breast-feeding high in both studies [70,71]. The Mitra study was an open-label, nonrandomized, prospective cohort study in Tanzania, in which infants were treated with AZT and 3TC from birth to 1 week of age and then with 3TC alone during breastfeeding, for a maximum of 6 months. The Kaplan–Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI 0.0–2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI 5.7–11.4). The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than that in the breastfeeding population of Petra arm A (relative hazard = 2.61; P = 0.001; adjusted values) [71].

Comparing maternal highly active antiretroviral therapy and infant prophylaxis

Direct comparison of the results of these studies to date is not possible in most cases, as duration and type of maternal treatment and antiretroviral drugs used for infant prophylaxis, duration of breastfeeding and extent of exclusive breastfeeding are different, but the data suggest that these strategies may have a place in the future [61•].

One trial, reported at the IAS 2009 conference, has compared the two strategies against a standard NVP regimen. The Breastfeeding Antiretroviral and Nutrition (BAN) study [72], in Malawi, is a randomized controlled trial of mother–infant pairs, evaluating two antiretroviral interventions over 24 weeks of exclusive breastfeeding followed by a 4-week period of weaning, among women with CD4 cell counts more than 250 cells/μl with infants uninfected at birth and weighing over 2000 g. All mothers and infants received single-dose NVP and 1-week AZT/3TC ‘tail’ coverage, and also nutritional supplementation. Mother and infants were randomized to receive either maternal HAART (AZT along with 3TC and either NVP, nelfinavir or LPV/r as guidelines for higher CD4 cell count pregnant women changed over the time of the study), or NVP infant prophylaxis or postpartum nutritional supplementation alone, as the control. In contrast to the other reported studies, maternal HAART was started after birth. Among 2637 mother–infant pairs, in-utero transmission was 4.9% (measured as HIV-1 infection at 1 week). The control arm, with no additional postpartum treatment after the standard regimen, was stopped by the Data Safety Monitoring Board (DSMB) study. The results presented show that both the infant NVP and maternal HAART regimens significantly reduced HIV transmission to the infants at 28 weeks compared with the enhanced control arm. Transmission in the infant NVP arm was 1.8 vs. 6.4% in the control arm, (P<0.0001), and in the maternal HAART arm, the transmission rate was 3.0 vs. 6.4% in the control arm (P= 0.0032). The estimated risk of HIV-1 transmission or death by 28 weeks was 7.6% in the control arm compared with 4.7% in the maternal HAART arm (P = 0.03) and 2.9% in the infant NVP arm (P<0.0001). This study was not powered for comparisons between the two intervention arms, but has shown a trend toward the infant extended prophylaxis being more effective for HIV-free survival of infants.

As with the other studies above, these data do not extend out past 6 months and longer follow-up results would be helpful for policy development. A large, multinational study is commencing in late 2009 within the International Maternal, Pediatric Adolescent AIDS Clinical trials (IMPAACT) network [the P1077 PROmoting Maternal and Infant Survival Everywhere (PROMISE) trial], which will compare maternal HAART vs. antenatal AZT and intrapartum NVP, and also maternal HAART vs. extended NVP prophylaxis to infants, with these interventions continued through the full duration of breastfeeding.

Conclusion

There have been several recent research advances in the use of antiretrovirals in pregnancy and to prevent breast milk transmission. These are likely to be reflected in new international guidelines, with revised advice to start antiretrovirals at a CD4 cell count of 350 cells/μl or less and to use some form of antiretroviral prophylaxis through breastfeeding. Ongoing research in the IMPAACT P1077 PROMISE trial will provide further information in the future as to the best of these approaches to reduce transmission through breastfeeding, and whether stopping prophylactic HAART has any long-term adverse impact on maternal health. Translation of these research findings into real impact depends on the improvement of services to reach and care for HIV-infected mothers and their children [48,7377]. Without significant efforts to improve the coverage and quality of PMTCT services and better use of these to provide access to ongoing treatment for women, we will not achieve the maximum benefit from antiretroviral use in pregnancy in low-resource settings.

Acknowledgments

James McIntyre is partly supported by the US National Institute of Allergy and Infectious Diseases (NIAID) through Grants U19 AI5321 and U01 AI068632, which facilitated work on this manuscript. The content of this publication does not necessarily reflect the views or policies of NIAID, nor does mention of trade names, commercial projects, or organizations imply endorsement by the US Government.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest

•• of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 105–106).

1••. UNAIDS. AIDS epidemic update 2008. Geneva: UNAIDS; 2008. Annual update on the epidemic.
2. UNAIDS. AIDS epidemic update: December 2007. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO); 2007.
3. Ziraba AK, Madise N, Mills S, et al. Maternal mortality in the informal settlements of Nairobi city: what do we know? Reprod Health. 2009;6:6. [PMC free article] [PubMed]
4•. Chersich MF, Luchters SM, Yard E, et al. Morbidity in the first year postpartum among HIV-infected women in Kenya. Int J Gynaecol Obstet. 2008;100:45–51. Impact of HIV on maternal mortality in Kenya. [PubMed]
5. Mataka E. Maternal health and HIV: bridging the gap. Lancet. 2007;370:1290–1291. [PubMed]
6. Department of Health, South Africa. The National HIV and Syphilis prevalence survey, South Africa 2007. Pretoria: Department of Health, South Africa; 2008.
7•. Black V, Brooke S, Chersich MF. Effect of human immunodeficiency virus treatment on maternal mortality at a tertiary center in South Africa: a 5-year audit. Obstet Gynecol. 2009;114(2 Pt 1):292–299. Impact of HIV on maternal mortality in South Africa, showing little effect to date of antiretroviral access on overall maternal mortality ratio in a tertiary care setting. [PubMed]
8••. World Health Organisation. Progress Report 2008. Geneva: World Health Organisation; 2008. Towards universal access. Scaling up priority HIV/AIDS interventions in the health sector. Comprehensive description of global progress on providing universal access to antiretroviral treatment.
9. UNAIDS. UNAIDS/08.36E. Geneva: UNAIDS; 2008. AIDS outlook: World AIDS Day 2008.
10•. Spensley A, Sripipatana T, Turner AN, et al. Preventing mother-to-child transmission of HIV in resource-limited settings: the Elizabeth Glaser Pediatric AIDS Foundation experience. Am J Public Health. 2009;99:631–637. Description of successful large-scale PMTCT scale-up in low-resource countries. [PubMed]
11. Potter D, Goldenberg RL, Chao A, et al. Do targeted HIV programs improve overall care for pregnant women? Antenatal syphilis management in Zambia before and after implementation of prevention of mother-to-child HIV transmission programs. J Acquir Immune Defic Syndr. 2008;47:79–85. [PMC free article] [PubMed]
12•. Tonwe-Gold B, Ekouevi DK, Bosse CA, et al. Implementing family-focused HIV care and treatment: the first 2 years’ experience of the mother-to-child transmission-plus program in Abidjan, Cote d’Ivoire. Trop Med Int Health. 2009;14:204–212. West African experience of PMTCT and treatment program. [PMC free article] [PubMed]
13. Chi BH, Chintu N, Lee A, et al. Expanded services for the prevention of mother-to-child HIV transmission: field acceptability of a pilot program in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2007;45:125–127. [PubMed]
14. World Health Organization. TB/HIV: a clinical manual. 2. Geneva: World Health Organisation; 2004.
15. Chandisarewa W, Stranix-Chibanda L, Chirapa E, et al. Routine offer of antenatal HIV testing (‘opt-out’ approach) to prevent mother-to-child transmission of HIV in urban Zimbabwe. Bull World Health Organ. 2007;85:843–850. [PubMed]
16. Creek TL, Ntumy R, Seipone K, et al. Successful introduction of routine opt-out HIV testing in antenatal care in Botswana. J Acquir Immune Defic Syndr. 2007;45:102–107. [PubMed]
17. World Health Organization. Recommendations for a Public Health Approach. 2006 version. Geneva: World Health Organization; 2006. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants in resource-limited settings: towards universal access.
18••. Perinatal HIV Guidelines Working Group, Public Health Service Task Force. Washington DC: US Public Health Service Task Force; Apr 292009. [Accessed 4 September 2009]. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. http://aidsin-fo.nih.gov/ContentFiles/PerinatalGL.pdf. Updates treatment guidelines for pregnancy in the United States.
19•• . de Ruiter A, Mercey D, Anderson J, et al. British HIV Association and Children’s HIV Association guidelines for the management of HIV infection in pregnant women (BHIVA) 2008. HIV Med. 2008;9:452–502. British HIV in pregnancy treatment guidelines. [PubMed]
20. Townsend C, Cortina-Borja M, Peckham C, Tookey P. Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990–2006. BJOG. 2008;115:1078–1086. [PubMed]
21. Townsend CL, Cortina-Borja M, Peckham CS, et al. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000–2006. AIDS. 2008;22:973–981. [PubMed]
22. Townsend C, Cortina-Borja M, Peckham C, et al. Very low risk of mother-to-child transmission in women on HAART who achieve viral suppression: the UK and Ireland, 2000 to 2006 [abstract 653]. 15th Conference on Retroviruses and Opportunistic Infections; 3–6 February 2008; Boston, MA. 2008.
23. Fowler MG, Lampe MA, Jamieson DJ, et al. Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions. Am J Obstet Gynecol. 2007;197 (3 Suppl):S3–S9. [PubMed]
24. European Collaborative study. The mother-to-child HIV transmission epidemic in Europe: evolving in the East and established in the West. AIDS. 2006;20:1419–1427. [PubMed]
25. Marazzi MC, Nielsen-Saines K, Buonomo E, et al. Increased infant human immunodeficiency virus-type one free survival at one year of age in sub-Saharan Africa with maternal use of highly active antiretroviral therapy during breast-feeding. Pediatr Infect Dis J. 2009;28:483–487. [PubMed]
26. Palombi L, Marazzi MC, Voetberg A, Magid NA. Treatment acceleration program and the experience of the DREAM program in prevention of mother-to-child transmission of HIV. AIDS. 2007;21 (Suppl 4):S65–S71. [PubMed]
27. Giuliano M, Guidotti G, Andreotti M, et al. Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load: a study within the Drug Resource Enhancement Against AIDS and Malnutrition Program. J Acquir Immune Defic Syndr. 2007;44:286–291. [PubMed]
28•. Areechokchai D, Bowonwatanuwong C, Phonrat B, et al. Pregnancy outcomes among HIV-infected women undergoing antiretroviral therapy. Open AIDS J. 2009;3:8–13. HIV and pregnancy outcomes in Thailand. [PMC free article] [PubMed]
29•. Machado ES, Hofer CB, Costa TT, et al. Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus after conception. Sex Transm Infect. 2009;85:82–87. HIV and pregnancy outcomes in Brazil. [PMC free article] [PubMed]
30. Ono E, Dos Santos AM, Machado DM, et al. Immunologic features of HIV-1-infected women on HAART at delivery. Cytometry B Clin Cytom. 2008;74:236–243. [PubMed]
31•. Ekouevi DK, Coffie PA, Becquet R, et al. Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Cote d’Ivoire. AIDS. 2008;22:1815–1820. HIV and pregnancy outcomes in Côte d’Ivoire. [PubMed]
32. Boeke CE, Jackson JB. Estimate of infant HIV-free survival at 6 to 8 weeks of age due to maternal antiretroviral prophylaxis in sub-Saharan Africa, 2004–2005. J Int Assoc Physicians AIDS Care (Chic Ill) 2008;7:133–140. [PubMed]
33. Suksomboon N, Poolsup N, Ket-Aim S. Systematic review of the efficacy of antiretroviral therapies for reducing the risk of mother-to-child transmission of HIV infection. J Clin Pharm Ther. 2007;32:293–311. [PubMed]
34••. Arrive E, Dabis F. Prophylactic antiretroviral regimens for prevention of mother-to-child transmission of HIV in resource limited settings. Curr Opin HIV AIDS. 2008;3:161–165. Review of PMTCT trial results in low resource settings. [PMC free article] [PubMed]
35. van Zyl GU, Claassen M, Engelbrecht S, et al. Zidovudine with nevirapine for the prevention of HIV mother-to-child transmission reduces nevirapine resistance in mothers from the Western Cape, South Africa. J Med Virol. 2008;80:942–946. [PubMed]
36•. Chigwedere P, Seage GR, Lee TH, Essex M. Efficacy of antiretroviral drugs in reducing mother-to-child transmission of HIV in Africa: a meta-analysis of published clinical trials. AIDS Res Hum Retroviruses. 2008;24:827–837. Meta-analysis of African studies demonstrating the efficacy of antiretroviral prophylaxis for PMTCT. [PubMed]
37•. Leroy V, Ekouevi DK, Becquet R, et al. 18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission. PLoS One. 2008;3:e1645. West African experience of antiretroviral prophylaxis. [PMC free article] [PubMed]
38. Martinson NA, Morris L, Johnson J, et al. Women exposed to single-dose nevirapine in successive pregnancies: effectiveness and nonnucleoside reverse transcriptase inhibitor resistance. AIDS. 2009;27:809–816. [PubMed]
39. Lehman DA, Chung MH, Mabuka JM, et al. Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. J Acquir Immune Defic Syndr. 2009;51:522–529. [PMC free article] [PubMed]
40. Lockman S, McIntyre JA. Reduction of HIV-1 drug resistance after intrapartum single-dose nevirapine. Lancet. 2007;370:1668–1670. [PubMed]
41. Walter J, Kuhn L, Kankasa C, et al. Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: a cohort study. BMC Infect Dis. 2008;8:172. [PMC free article] [PubMed]
42. Wind-Rotolo M, Durand C, Cranmer L, et al. Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. J Infect Dis. 2009;199:1301–1309. [PMC free article] [PubMed]
43. Han J, Wang L, Jiang Y, et al. Resistance mutations in HIV-1 infected pregnant women and their infants receiving antiretrovirals to prevent HIV-1 vertical transmission in China. Int J STD AIDS. 2009;20:249–254. [PubMed]
44••. Moorthy A, Gupta A, Bhosale R, et al. Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS One. 2009;4:e4096. Resistance in all infants infected despite extended NVP prophylaxis. [PMC free article] [PubMed]
45. Coovadia A, Hunt G, Abrams EJ, et al. Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Clin Infect Dis. 2009;48:462–472. [PMC free article] [PubMed]
46. Jackson DJ, Chopra M, Doherty TM, et al. Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-1. AIDS. 2007;21:509–516. [PubMed]
47•. Goga AE, Van Wyk B, Doherty T, et al. Operational effectiveness of guidelines on complete breast-feeding cessation to reduce mother-to-child transmission of HIV: results from a prospective observational cohort study at routine prevention of mother-to-child transmission sites, South Africa. J Acquir Immune Defic Syndr. 2009;50:521–528. Demonstration of the importance of programmatic issues affecting PMTCT outcomes. [PubMed]
48. McIntyre J, Lallemant M. The prevention of mother-to-child transmission of HIV: are we translating scientific success into programmatic failure? Curr Opin HIV AIDS. 2008;3:139–145. [PubMed]
49. Coovadia HM, Rollins NC, Bland RM, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet. 2007;369:1107–1116. [PubMed]
50••. Kuhn L, Reitz C, Abrams EJ. Breastfeeding and AIDS in the developing world. Curr Opin Pediatr. 2009;21:83–93. Extensive review of breastfeeding issues. [PubMed]
51. Rollins NC, Becquet R, Bland RM, et al. Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes. AIDS. 2008;22:2349–2357. [PMC free article] [PubMed]
52. Becquet R, Bland R, Leroy V, et al. Duration and pattern of breastfeeding and postnatal transmission of HIV: pooled analysis of individual data from a West and South African Cohort study [abstract 46]. 15th Conference on Retroviruses and Opportunistic Infections; 3–6 February 2008; Boston, MA. 2008.
53. World Health Organization. WHO HIV and Infant Feeding Technical Consultation. Held on behalf of the Inter-agency Task Team (IATT) on Prevention of HIV Infections in Pregnant Women, Mothers and their Infants; 25–27 October 2006; Geneva. [Accessed 3 January 2008]. Consensus Statement [Web Page]. http://www.who.int/reproductive-health/stis/mtct/infantfeedingconsensusstatement.pdf.
54••. Arpadi S, Fawzy A, Aldrovandi GM, et al. Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia. Am J Clin Nutr. 2009;90:344–353. Adverse effect of early cessation of breastfeeding in a very low-resource setting. [PubMed]
55. Kafulafula G, Thigpen M, Hoover D, et al. Postweaning gastroenteritis and mortality in HIV-uninfected African infants receiving antiretroviral prophylaxis to prevent MTCT of HIV-1 [abstract 773]. 14th Conference on Retroviruses and Opportunistic Infections; 25–28 February 2007; Los Angeles, California.
56. Kuhn L, Aldrovandi GM, Sinkala M, et al. Effects of early, abrupt weaning on HIV-free survival of children in Zambia. N Engl J Med. 2008;359:130–141. [PMC free article] [PubMed]
57. Fox MP, Brooks D, Kuhn L, et al. Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia. J Acquir Immune Defic Syndr. 2008;48:90–96. [PMC free article] [PubMed]
58. Creek T, Arvelo W, Kim W, et al. A large outbreak of diarrhea with high mortality among nonbreastfed children in Botswana, 2006 – implications for HIV prevention strategies and child health. 14th Conference on Retroviruses and Opportunistic Infections; 25–28 February 2007; Los Angeles, CA, USA. [Accessed 2 May 2009]. http://www.retroconference.org/2007/Abstracts/30582.htm.
59. Kuhn L, Aldrovandi GM, Sinkala M, et al. Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease. PLoS One. 2009;4:e6059. [PMC free article] [PubMed]
60. Fox MP, Brooks DR, Kuhn L, et al. Role of breastfeeding cessation in mediating the relationship between maternal HIV disease stage and increased child mortality among HIV-exposed uninfected children. Int J Epidemiol. 2009;38:569–576. [PMC free article] [PubMed]
61•. Mofenson LM. Antiretroviral prophylaxis to reduce breast milk transmission of HIV type 1: new data but still questions. J Acquir Immune Defic Syndr. 2008;48:237–240. Commentary on antiretroviral prophylaxis for breast milk transmission. [PubMed]
62. World Health Organization. WHO Expert Consultation on new and emerging evidence on the use of antiretroviral drugs for the prevention of mother-to-child transmission of HIV; 17–19 November 2008; Geneva. [Accessed 4 September 2009]. http://www.who.int/hiv/topics/mtct/mtct_conclusions_consult.pdf.
63. Kilewo C, Karlsson K, Ngarina M, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra plus study. J Acquir Immune Defic Syndr. 2009 doi: 10.1097/QAI.0b013e3181b323ff. Epub ahead of print. [PubMed] [Cross Ref]
64. Peltier CA, Ndayisaba GF, Lepage P, et al. Breastfeeding with maternal antiretroviral therapy or formula feeding to prevent HIV postnatal mother-to-child transmission in Rwanda. AIDS. 2009 doi: 10.1097/QAD.0b013e32832ec20d. Epub ahead of print. [PMC free article] [PubMed] [Cross Ref]
65. Thomas T, Masaba R, Ndivo R, et al. Prevention of mother-to-child transmission of HIV-1 among breastfeeding mothers using HAART: the Kisumu Breastfeeding study, Kisumu, Kenya, 2003–2007 [abstract 45aLB]. 15th Conference on Retroviruses and Opportunistic Infections; 3–6 February 2008; Boston, MA.
66. de Vincenzi I. Kesho Bora Study Group. Triple-antiretroviral (ARV) prophylaxis during pregnancy and breastfeeding compared to short-ARV prophylaxis to prevent mother-to-child transmission of HIV-1 (MTCT): the Kesho Bora randomized controlled clinical trial in five sites in Burkina Faso, Kenya [abstract LBPEC01]. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 19–22 July 2009; Cape Town, South Africa.
67. Shapiro R, Hughes M, Ogwu A, et al. A randomized trial comparing highly active antiretroviral therapy regimens for virologic efficacy and the prevention of mother-to-child HIV transmission among breastfeeding women in Botswana (The Mma Bana study) [abstract WELB101]. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 19–22 July 2009; Cape Town, South Africa.
68••. Bedri A, Gudetta B, Isehak A, et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008;372:300–313. Results from the SWEN study of extended nevirapine prophylaxis. [PubMed]
69••. Kumwenda NI, Hoover DR, Mofenson LM, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008;359:119–129. Results from the PEPI Malawi extended NVP infant prophylaxis study. [PubMed]
70. Vyankandondera J, Luchters S, Hassink E, et al. Reducing risk of HIV-1 transmission from mother to infant through breastfeeding using antiretroviral prophylaxis in infants (SIMBA study) [abstract No. LB7]. 2nd IAS Conference on HIV Pathogenesis and Treatment; 13–16 July 2003.
71. Kilewo C, Karlsson K, Massawe A, et al. Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra study. J Acquir Immune Defic Syndr. 2008;48:315–323. [PubMed]
72. Chasela C, Hudgens M, Jamieson D, et al. Both maternal HAART and daily infant nevirapine (NVP) are effective in reducing HIV-1 transmission during breastfeeding in a randomized trial in Malawi: 28 week results of the Breastfeeding, Antiretroviral and Nutrition (BAN) study [abstract WELBC103]. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 19–22 July 2009; Cape Town, South Africa.
73. Mazia G, Narayanan I, Warren C, et al. Integrating quality postnatal care into PMTCT in Swaziland. Glob Public Health. 2009;4:253–270. [PubMed]
74. Mate KS, Bennett B, Mphatswe W, et al. Challenges for routine health system data management in a large public programme to prevent mother-to-child HIV transmission in South Africa. PLoS One. 2009;4:e5483. [PMC free article] [PubMed]
75. Paintsil E, Andiman WA. Update on successes and challenges regarding mother-to-child transmission of HIV. Curr Opin Pediatr. 2009;21:94–101. [PMC free article] [PubMed]
76. Coovadia H. Current issues in prevention of mother-to-child transmission of HIV-1. Curr Opin HIV AIDS. 2009;4:319–324. [PubMed]
77. Abrams EJ, Myer L, Rosenfield A, El-Sadr WM. Prevention of mother-to-child transmission services as a gateway to family-based human immunodeficiency virus care and treatment in resource-limited settings: rationale and international experiences. Am J Obstet Gynecol. 2007;197 (3 Suppl):S101–S106. [PubMed]