Maternal or infant antiretroviral drugs to reduce HIV-1 transmission

Charles S Chasela, Michael G Hudgens, Denise J Jamieson, Dumbani Kayira, Mina C Hosseinipour, Athena P Kourtis, Francis Martinson, Gerald Tegha, Rodney J Knight, Yusuf I Ahmed, Deborah D Kamwendo, Irving F Hoffman, Sascha R Ellington, Zebrone Kacheche, Alice Soko, Jeffrey B Wiener, Susan A Fiscus, Peter Kazembe, Innocent A Mofolo, Maggie Chigwenembe, Dorothy S Sichali, Charles M van der Horst, BAN Study Group, L Adair, Y Ahmed, M Ait-Khaled, S Albrecht, S Bangdiwala, R Bayer, M Bentley, B Bramson, E Bobrow, N Boyle, S Butera, C Chasela, C Chavula, J Chimerang'ambe, M Chigwenembe, M Chikasema, N Chikhungu, D Chilongozi, G Chiudzu, L Chome, A Cole, A Corbett, A Corneli, A Cross, A Duerr, H Eliya, S Ellington, J Eron, S Farr, Y Owens Ferguson, S Fiscus, S Galvin, L Guay, C Heilig, I Hoffman, E Hooten, M Hosseinipour, M Hudgens, S Hurst, L Hyde, D Jamieson, G Joaki, D Jones, Z Kacheche, E Kamanga, G Kamanga, C Kampani, P Kamthunzi, D Kamwendo, C Kanyama, A Kashuba, D Kathyola, D Kayira, P Kazembe, C King, R Knight, A Kourtis, R Krysiak, J Kumwenda, E Loeliger, D Long, M Luhanga, V Madhlopa, M Majawa, A Maida, C Marcus, F Martinson, C Matiki, D Mayers, I Mayuni, M McDonough, J Meme, C Merry, K Mita, C Mkomawanthu, G Mndala, I Mndala, A Moses, A Msika, W Msungama, B Mtimuni, J Muita, N Mumba, B Musis, C Mwansambo, G Mwapasa, J Nkhoma, R Pendame, E Piwoz, B Raines, Z Ramdas, J Rublein, M Ryan, I Sanne, C Sellers, D Shugars, D Sichali, S-B Smith, W Snowden, A Soko, A Spensley, J-M Steens, G Tegha, M Tembo, R Thomas, N Thoofer, H-C Tien, B Tohill, C van der Horst, E Waalberg, J Wiener, C Wilfert, P Wiyo, I Zgambo, C Zimba, Charles S Chasela, Michael G Hudgens, Denise J Jamieson, Dumbani Kayira, Mina C Hosseinipour, Athena P Kourtis, Francis Martinson, Gerald Tegha, Rodney J Knight, Yusuf I Ahmed, Deborah D Kamwendo, Irving F Hoffman, Sascha R Ellington, Zebrone Kacheche, Alice Soko, Jeffrey B Wiener, Susan A Fiscus, Peter Kazembe, Innocent A Mofolo, Maggie Chigwenembe, Dorothy S Sichali, Charles M van der Horst, BAN Study Group, L Adair, Y Ahmed, M Ait-Khaled, S Albrecht, S Bangdiwala, R Bayer, M Bentley, B Bramson, E Bobrow, N Boyle, S Butera, C Chasela, C Chavula, J Chimerang'ambe, M Chigwenembe, M Chikasema, N Chikhungu, D Chilongozi, G Chiudzu, L Chome, A Cole, A Corbett, A Corneli, A Cross, A Duerr, H Eliya, S Ellington, J Eron, S Farr, Y Owens Ferguson, S Fiscus, S Galvin, L Guay, C Heilig, I Hoffman, E Hooten, M Hosseinipour, M Hudgens, S Hurst, L Hyde, D Jamieson, G Joaki, D Jones, Z Kacheche, E Kamanga, G Kamanga, C Kampani, P Kamthunzi, D Kamwendo, C Kanyama, A Kashuba, D Kathyola, D Kayira, P Kazembe, C King, R Knight, A Kourtis, R Krysiak, J Kumwenda, E Loeliger, D Long, M Luhanga, V Madhlopa, M Majawa, A Maida, C Marcus, F Martinson, C Matiki, D Mayers, I Mayuni, M McDonough, J Meme, C Merry, K Mita, C Mkomawanthu, G Mndala, I Mndala, A Moses, A Msika, W Msungama, B Mtimuni, J Muita, N Mumba, B Musis, C Mwansambo, G Mwapasa, J Nkhoma, R Pendame, E Piwoz, B Raines, Z Ramdas, J Rublein, M Ryan, I Sanne, C Sellers, D Shugars, D Sichali, S-B Smith, W Snowden, A Soko, A Spensley, J-M Steens, G Tegha, M Tembo, R Thomas, N Thoofer, H-C Tien, B Tohill, C van der Horst, E Waalberg, J Wiener, C Wilfert, P Wiyo, I Zgambo, C Zimba

Abstract

Background: We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi.

Methods: We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test.

Results: Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction.

Conclusions: The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)

Conflict of interest statement

No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

2010 Massachusetts Medical Society

Figures

Figure 1. Enrollment and Outcomes
Figure 1. Enrollment and Outcomes
On March 26, 2008, the data and safety monitoring board stopped enrollment in the control group after 668 of the planned 806 mother–infant pairs had been assigned to that group. Hence, the numbers of patients who were enrolled in the three study groups were uneven. Of the 29 infants who died during the study from non–HIV-1 causes, each had had a negative test for HIV-1 before death.
Figure 2. Kaplan–Meier Estimates of the Cumulative…
Figure 2. Kaplan–Meier Estimates of the Cumulative Risk of Infant HIV-1 Infection or a Composite of HIV-1 Infection or Death by 28 Weeks
Shown is the probability of HIV-1 infection or a composite of HIV-1 infection or death among infants who tested negative for HIV-1 infection at 2 weeks (Panels A and B) and among all infants who underwent randomization (Panels C and D) in three groups of mother–infants pairs: women who received an antiretroviral (ARV) regimen, infants who received nevirapine (NVP) prophylaxis, and control subjects. Rates were compared with the use of the log-rank test.

Source: PubMed

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