Effectiveness and Safety of Combination Therapy of Zidovudine and Lamivudine for Preventing the Risk of Mother-to-Child Transmission of HIV: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Li ¹ , MAO Xiu ² , MENG Yue ² , PENG Lihua ² , SUN Xin ¹ , JING Yuanyuan ² , LIU Guanjian ¹ ,  LI Youping ¹

1.Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China2.West China Medical School, Sichuan University;

Corresponding author：

LI Youping, Email: yzmylab@hotmail.com

Keywords：

HIV; Mother-to-child transmission; Zidovudine; Lamivudine; Nevirapine; Systematic review

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To assess the effectiveness and safety of combination therapy of zidovudine and lamivudine (ZDV+3TC) for preventing mother-to-child transmission (MTCT) of HIV.
Methods 　A systematic review of randomized controlled trials (RCTs) was conducted using the methodology of The Cochrane Collaboration. PUBMED, EMBASE, CINAHL, AIDSearch, AIDSLINE, AIDSTRIALS, The Cochrane Library (Issue 2, 2007), AIDSDRUGS, AIDSinfo, CRD (Center of Review and Dissemination) databases and three Chinese Databases (CBM, CNKI, VIP) were searched from their establishment to 31 May 2007. We also searched documents of governmental and non-governmental organizations (NGOs), and the proceedings of relevant conferences, including the International AIDS Conferences, and the annual Conference on Retroviruses and Opportunistic Infections. RCTs assessing the effects of ZDV+3TC for preventing MTCT were included. Trial selection, quality assessment and data extraction were done by two reviewers independently. Different opinions were resolved by discussion with a third party. Meta-analyses were conducted using The Cochrane Collaboration’s RevMan 4.2.9 software.
Results 　Three studies in breastfeeding populations were included. One trial (PETRA, 1797 participants) found that ZDV+3TC decreased the risk of transmission by 35%-65% within 15 months compared with placebo. However, there was no evidence that ultra-short course ZDV+3TC (during labor) decreased the risk of transmission, compared with placebo. The safety of different courses of ZDV+3TC and placebo were similar (P gt;0.05). Another trial (SAINT, 1317 participants) found that short course ZDV+3TC (from 36weeks gestation to labor) did not significantly reduce HIV infection among children at 8 weeks after delivery, when compared with single dose nevirapine given to the mother and the infant (P gt;0.05). No significant difference was found in the maternal and infants mortality and side effects of two groups. One small trial (Moodley1998, 20 participants) found no infant infection in both ZDV+3TC and 3TC alone within 2 weeks after birth.
Conclusions 　Long course (from 36 weeks gestation to 1 week after delivery) and short course (from 36 weeks gestation to labor) ZDV+3TC were more effective than placebo in preventing MTCT of HIV in breastfeeding women with a similar safety profile. Short course ZDV + 3TC had similar effects to single dose nevirapine, and long course ZDV + 3TC had similar effects to lamivudine alone.

Citation： WANG Li,MAO Xiu,MENG Yue,PENG Lihua,SUN Xin,JING Yuanyuan,LIU Guanjian,LI Youping. Effectiveness and Safety of Combination Therapy of Zidovudine and Lamivudine for Preventing the Risk of Mother-to-Child Transmission of HIV: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2007, 07(7): 487-495. doi: Copy

1.	Wang L, MengY, Mao X, et al. Effectiveness and Safety of Zidovudine for Preventing the Risk of Mother-to-Child Transmission of HIV: A Systematic Review. Chinese Journal of Evidence-based Medicine, 2007, 7(5): 367-384.
2.	Li TS, et al. the AIDS guideline group of Chinese Medical Associate. Guideline of AIDS diagnosis and therapy. http://www.moh.gov.cn/newshtml/9266.htm.
3.	Nation group of Handbook for the free antiretroviral therapy of HIV. Nation Free medical Information Handbook for the antiretroviral therapy of HIV. 2004. 12.
4.	Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. New Engl J Med, 1994, 331: 1173-1180.
5.	Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet, 1999, 354(9181): 795-802.
6.	Brocklehurst P, Volmink J. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD003510. DOI: 10. 1002/14651858.CD003510.
7.	Brocklehurst, P. and Volmink, J. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. The Cochrane Library. 2006 Issue 1. CD003510.
8.	王莉, 孟月, 毛秀, 等. 齐多夫定单用预防HIV母婴传播有效性和安全性的系统评价. 中国循证医学杂志, 2007, 7(5): 367-384.
9.	Culnane M, Fowler MG, Lee S, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected childen born to HIV-infected women. JAMA, 1991, 281: 151-157.
10.	Allen UD, Conway B, Lapointe N, et al. Zidovudine resistance and associated factors among HIV-infected Canadian children. Int Conf AIDS, 996, 11: 311 (abstract no. Th.B.4353).
11.	Delvaux, Therese. Nevirapine sustains reduction of mother-to-child HIV transmission at 18 months. Evidence-Based Healthcare, 2004, 8(2): 87-88.
12.	Arrive E, Newell ML, Ekouevi DK, et al. Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis. Int J Epidemiol: dym104v1-13. 2007 May 28.
13.	The PETRA Study Team. Efficacy of three shortcourse regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (PETRA study): a randomized, double-blind, placebo-controlled trial. Lancet, 2002, 359: 1178-1186.
14.	Moodley D, McIntyre J. Evaluation of safety and efficacy of two simple regimens for the prevention of mother to child transmission(MTCT) of HIV-infection: nevirapine vs. lamivudine and zidovudine used in a randomized clinical trial (the SAINT study). XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract TuOrB356.
15.	Dorenbaum A, Cunningham CK, Gelber RD, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission. JAMA, 2002, 288(2): 189-198.
16.	World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants.Guidelines on care, treatment and support for women living with HIV/AIDS and their children in resource-constrained settings. Geneva, 2004 (http://www.who.int/hiv/pub/mtct/guidelines/en/, accessed 19 June 2006).
17.	李太生, 等（中华医学会艾滋病指南撰写组）. 艾滋病诊疗指南. 中国卫生部网站http://www.moh.gov.cn/newshtml/9266.htm.
18.	国家免费艾滋病抗病毒药物治疗手册编写组. 国家免费艾滋病抗病毒药物治疗手册. 2004. 12.
19.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
20.	Giuliano M, Palmisano L, Galluzzo CM, et al. Selection of resistance mutations in pregnant women receiving zidovudine and lamivudine to prevent HIV perinatal transmission. AIDS, 2003, 17(10): 1570-1572.
21.	Saba J. Interim analysis of early efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1: the PETRA trial. 6th Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4; 212: abstract no. S7.
22.	Saba J. The results of the PETRA intervention trial to prevent perinatal transmission in sub-Saharan Africa. Chicago: Foundation for Retrovirology and Human Health,, 1999. (See http://www.retroconference.org/99/lect_symposia/sym_session8.htm.) (See NAPS document no. 05531 for 19 pages, c/o Microfiche Publications, 248 Hempstead Tpke, West Hempstead, NY 11552.).
23.	Mcintyre JA, Gray GE. The Effect of Mode of Delivery and Other Variables on the Early Efficacy of Three Short ZDV/3TC Combination Regimens to Prevent Mother-to-Child Transmission of HIV-1: the PETRA Trial. Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 478; abstract no. 585.
24.	Gray G. The PETRA study: early and late efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1. Int Conf AIDS 2000 Jul 9-14; 13:17; abstract no. LbOr5.
25.	Giuliano M, Galluzzo T, Amici R, et al. Selection of Resistance Mutations in Pregnant Women Receiving Short-Course Antiretroviral Regimens with ZDV and 3TC to Prevent Perinatal Transmission (PETRA Study). 9th Conference on Retroviruses and Opportunistic Infections. 2002 Feb 24-28, 9: abstract no. 802-W.
26.	Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. Journal of Infectious Diseases, 2003, 187(5): 725-735.
27.	McIntyre J. Evaluation of safety of two simple regimens for prevention of mother to child transmission (MTCT) of HIV infection ’Nevirapine (NVP) vs lamivudine (3TC)+zidovudine (ZDV)’ used in a randomized clinical trial (The SAINT Study).International Conference on AIDS, South Africa 2000 Jul 9-14; 13: abstract no. TuOrB356.
28.	Moodley D, McIntyre J. Evaluation of safety and efficacy of two simple regimens for the prevention of mother to child transmission (MTCT) of HIV infection: nevirapine vs lamivudine and zidovudine used in a randomised clinical trial (SAINT). XIII International AIDS Conference, Durban. 2000; Vol. Abstract TuOrB356.
29.	Moodley J, Moodley D, Pillay K, et al. Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministeredwith zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring. Journal of Infectious Diseases, 1998, 178(5): 1327-1333.
30.	Elliot Marseille, James G. Kahn, Joseph Saba. Cost-effectiveness of antiviral drug therapy to reduce mother-to-child HIV transmission in sub-Saharan Africa. AIDS, 1998, 12: 939-948.

1. Wang L, MengY, Mao X, et al. Effectiveness and Safety of Zidovudine for Preventing the Risk of Mother-to-Child Transmission of HIV: A Systematic Review. Chinese Journal of Evidence-based Medicine, 2007, 7(5): 367-384.
2. Li TS, et al. the AIDS guideline group of Chinese Medical Associate. Guideline of AIDS diagnosis and therapy. http://www.moh.gov.cn/newshtml/9266.htm.
3. Nation group of Handbook for the free antiretroviral therapy of HIV. Nation Free medical Information Handbook for the antiretroviral therapy of HIV. 2004. 12.
4. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. New Engl J Med, 1994, 331: 1173-1180.
5. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet, 1999, 354(9181): 795-802.
6. Brocklehurst P, Volmink J. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD003510. DOI: 10. 1002/14651858.CD003510.
7. Brocklehurst, P. and Volmink, J. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. The Cochrane Library. 2006 Issue 1. CD003510.
8. 王莉, 孟月, 毛秀, 等. 齐多夫定单用预防HIV母婴传播有效性和安全性的系统评价. 中国循证医学杂志, 2007, 7(5): 367-384.
9. Culnane M, Fowler MG, Lee S, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected childen born to HIV-infected women. JAMA, 1991, 281: 151-157.
10. Allen UD, Conway B, Lapointe N, et al. Zidovudine resistance and associated factors among HIV-infected Canadian children. Int Conf AIDS, 996, 11: 311 (abstract no. Th.B.4353).
11. Delvaux, Therese. Nevirapine sustains reduction of mother-to-child HIV transmission at 18 months. Evidence-Based Healthcare, 2004, 8(2): 87-88.
12. Arrive E, Newell ML, Ekouevi DK, et al. Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis. Int J Epidemiol: dym104v1-13. 2007 May 28.
13. The PETRA Study Team. Efficacy of three shortcourse regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (PETRA study): a randomized, double-blind, placebo-controlled trial. Lancet, 2002, 359: 1178-1186.
14. Moodley D, McIntyre J. Evaluation of safety and efficacy of two simple regimens for the prevention of mother to child transmission(MTCT) of HIV-infection: nevirapine vs. lamivudine and zidovudine used in a randomized clinical trial (the SAINT study). XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract TuOrB356.
15. Dorenbaum A, Cunningham CK, Gelber RD, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission. JAMA, 2002, 288(2): 189-198.
16. World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants.Guidelines on care, treatment and support for women living with HIV/AIDS and their children in resource-constrained settings. Geneva, 2004 (http://www.who.int/hiv/pub/mtct/guidelines/en/, accessed 19 June 2006).
17. 李太生, 等（中华医学会艾滋病指南撰写组）. 艾滋病诊疗指南. 中国卫生部网站http://www.moh.gov.cn/newshtml/9266.htm.
18. 国家免费艾滋病抗病毒药物治疗手册编写组. 国家免费艾滋病抗病毒药物治疗手册. 2004. 12.
19. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
20. Giuliano M, Palmisano L, Galluzzo CM, et al. Selection of resistance mutations in pregnant women receiving zidovudine and lamivudine to prevent HIV perinatal transmission. AIDS, 2003, 17(10): 1570-1572.
21. Saba J. Interim analysis of early efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1: the PETRA trial. 6th Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4; 212: abstract no. S7.
22. Saba J. The results of the PETRA intervention trial to prevent perinatal transmission in sub-Saharan Africa. Chicago: Foundation for Retrovirology and Human Health,, 1999. (See http://www.retroconference.org/99/lect_symposia/sym_session8.htm.) (See NAPS document no. 05531 for 19 pages, c/o Microfiche Publications, 248 Hempstead Tpke, West Hempstead, NY 11552.).
23. Mcintyre JA, Gray GE. The Effect of Mode of Delivery and Other Variables on the Early Efficacy of Three Short ZDV/3TC Combination Regimens to Prevent Mother-to-Child Transmission of HIV-1: the PETRA Trial. Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 478; abstract no. 585.
24. Gray G. The PETRA study: early and late efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1. Int Conf AIDS 2000 Jul 9-14; 13:17; abstract no. LbOr5.
25. Giuliano M, Galluzzo T, Amici R, et al. Selection of Resistance Mutations in Pregnant Women Receiving Short-Course Antiretroviral Regimens with ZDV and 3TC to Prevent Perinatal Transmission (PETRA Study). 9th Conference on Retroviruses and Opportunistic Infections. 2002 Feb 24-28, 9: abstract no. 802-W.
26. Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. Journal of Infectious Diseases, 2003, 187(5): 725-735.
27. McIntyre J. Evaluation of safety of two simple regimens for prevention of mother to child transmission (MTCT) of HIV infection ’Nevirapine (NVP) vs lamivudine (3TC)+zidovudine (ZDV)’ used in a randomized clinical trial (The SAINT Study).International Conference on AIDS, South Africa 2000 Jul 9-14; 13: abstract no. TuOrB356.
28. Moodley D, McIntyre J. Evaluation of safety and efficacy of two simple regimens for the prevention of mother to child transmission (MTCT) of HIV infection: nevirapine vs lamivudine and zidovudine used in a randomised clinical trial (SAINT). XIII International AIDS Conference, Durban. 2000; Vol. Abstract TuOrB356.
29. Moodley J, Moodley D, Pillay K, et al. Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministeredwith zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring. Journal of Infectious Diseases, 1998, 178(5): 1327-1333.
30. Elliot Marseille, James G. Kahn, Joseph Saba. Cost-effectiveness of antiviral drug therapy to reduce mother-to-child HIV transmission in sub-Saharan Africa. AIDS, 1998, 12: 939-948.

Chinese Journal of Evidence-Based Medicine

Effectiveness and Safety of Combination Therapy of Zidovudine and Lamivudine for Preventing the Risk of Mother-to-Child Transmission of HIV: A Systematic Review

Abstract Full text Figures/Tables Video References Cited by

Format

Content