Addition of 7 days of zidovudine plus lamivudine to peripartum single-dose nevirapine effectively reduces nevirapine resistance postpartum in HIV-infected mothers in Malawi

Sherry L Farr, Julie A E Nelson, Thokozani J Ng'ombe, Athena P Kourtis, Charles Chasela, Jeffrey A Johnson, Angela D M Kashuba, Gerald L Tegha, Jeffrey Wiener, Joseph J Eron, Harriet N Banda, Mwanangwa Mpaso, Jonathan Lipscomb, Chrissie Matiki, Susan A Fiscus, Denise J Jamieson, Charles van der Horst, BAN Study Team, Linda Adair, Yusuf Ahmed, Mounir Ait-Khaled, Sandra Albrecht, Shrikant Bangdiwala, Ronald Bayer, Margaret Bentley, Brian Bramson, Emily Bobrow, Nicola Boyle, Sal Butera, Charles Chasela, Charity Chavula, Joseph Chimerang'ambe, Maggie Chigwenembe, Maria Chikasema, Norah Chikhungu, David Chilongozi, Grace Chiudzu, Lenesi Chome, Anne Cole, Amanda Corbett, Amy Corneli, Ann Duerr, Henry Eliya, Sascha Ellington, Joseph Eron, Sherry Farr, Yvonne Owens Ferguson, Susan Fiscus, Shannon Galvin, Laura Guay, Chad Heilig, Irving Hoffman, Elizabeth Hooten, Mina Hosseinipour, Michael Hudgens, Stacy Hurst, Lisa Hyde, Denise Jamieson, George Joaki, David Jones, Zebrone Kacheche, Esmie Kamanga, Gift Kamanga, Coxcilly Kampani, Portia Kamthunzi, Deborah Kamwendo, Cecilia Kanyama, Angela Kashuba, Damson Kathyola, Dumbani Kayira, Peter Kazembe, Caroline King, Rodney Knight, Athena P Kourtis, Robert Krysiak, Jacob Kumwenda, Edde Loeliger, Misheck Luhanga, Victor Madhlopa, Maganizo Majawa, Alice Maida, Cheryl Marcus, Francis Martinson, Navdeep Thoofer, Chrissie Matiki, Douglas Mayers, Isabel Mayuni, Marita McDonough, Joyce Meme, Ceppie Merry, Khama Mita, Chimwemwe Mkomawanthu, Gertrude Mndala, Ibrahim Mndala, Agnes Moses, Albans Msika, Wezi Msungama, Beatrice Mtimuni, Jane Muita, Noel Mumba, Bonface Musis, Charles Mwansambo, Gerald Mwapasa, Jacqueline Nkhoma, Richard Pendame, Ellen Piwoz, Byron Raines, Zane Ramdas, John Rublein, Mairin Ryan, Ian Sanne, Christopher Sellers, Diane Shugars, Dorothy Sichali, Wendy Snowden, Alice Soko, Allison Spensley, Jean-Marc Steens, Gerald Tegha, Martin Tembo, Roshan Thomas, Hsiao-Chuan Tien, Beth Tohill, Charles van der Horst, Esther Waalberg, Jeffrey Wiener, Cathy Wilfert, Patricia Wiyo, Innocent Zgambo, Chifundo Zimba, Sherry L Farr, Julie A E Nelson, Thokozani J Ng'ombe, Athena P Kourtis, Charles Chasela, Jeffrey A Johnson, Angela D M Kashuba, Gerald L Tegha, Jeffrey Wiener, Joseph J Eron, Harriet N Banda, Mwanangwa Mpaso, Jonathan Lipscomb, Chrissie Matiki, Susan A Fiscus, Denise J Jamieson, Charles van der Horst, BAN Study Team, Linda Adair, Yusuf Ahmed, Mounir Ait-Khaled, Sandra Albrecht, Shrikant Bangdiwala, Ronald Bayer, Margaret Bentley, Brian Bramson, Emily Bobrow, Nicola Boyle, Sal Butera, Charles Chasela, Charity Chavula, Joseph Chimerang'ambe, Maggie Chigwenembe, Maria Chikasema, Norah Chikhungu, David Chilongozi, Grace Chiudzu, Lenesi Chome, Anne Cole, Amanda Corbett, Amy Corneli, Ann Duerr, Henry Eliya, Sascha Ellington, Joseph Eron, Sherry Farr, Yvonne Owens Ferguson, Susan Fiscus, Shannon Galvin, Laura Guay, Chad Heilig, Irving Hoffman, Elizabeth Hooten, Mina Hosseinipour, Michael Hudgens, Stacy Hurst, Lisa Hyde, Denise Jamieson, George Joaki, David Jones, Zebrone Kacheche, Esmie Kamanga, Gift Kamanga, Coxcilly Kampani, Portia Kamthunzi, Deborah Kamwendo, Cecilia Kanyama, Angela Kashuba, Damson Kathyola, Dumbani Kayira, Peter Kazembe, Caroline King, Rodney Knight, Athena P Kourtis, Robert Krysiak, Jacob Kumwenda, Edde Loeliger, Misheck Luhanga, Victor Madhlopa, Maganizo Majawa, Alice Maida, Cheryl Marcus, Francis Martinson, Navdeep Thoofer, Chrissie Matiki, Douglas Mayers, Isabel Mayuni, Marita McDonough, Joyce Meme, Ceppie Merry, Khama Mita, Chimwemwe Mkomawanthu, Gertrude Mndala, Ibrahim Mndala, Agnes Moses, Albans Msika, Wezi Msungama, Beatrice Mtimuni, Jane Muita, Noel Mumba, Bonface Musis, Charles Mwansambo, Gerald Mwapasa, Jacqueline Nkhoma, Richard Pendame, Ellen Piwoz, Byron Raines, Zane Ramdas, John Rublein, Mairin Ryan, Ian Sanne, Christopher Sellers, Diane Shugars, Dorothy Sichali, Wendy Snowden, Alice Soko, Allison Spensley, Jean-Marc Steens, Gerald Tegha, Martin Tembo, Roshan Thomas, Hsiao-Chuan Tien, Beth Tohill, Charles van der Horst, Esther Waalberg, Jeffrey Wiener, Cathy Wilfert, Patricia Wiyo, Innocent Zgambo, Chifundo Zimba

Abstract

Background: We assessed whether 7 days of zidovudine + lamivudine postpartum with single-dose nevirapine at labor decreases nevirapine resistance in HIV-infected women in Malawi.

Methods: HIV-infected pregnant women receiving intrapartum single-dose nevirapine and 7 days of zidovudine + lamivudine (n = 132) and women receiving intrapartum single-dose nevirapine alone (n = 66) were followed from an antenatal visit through 6 weeks postpartum. Plasma specimens at 2 and 6 weeks postpartum were tested for genotypic resistance to nevirapine by population sequencing and sensitive real-time polymerase chain reaction. Poisson regression was used to determine predictors of postpartum nevirapine resistance.

Results: Median HIV RNA was similar at entry (4.27 log vs. 4.35 log, P = 0.87), differed at 2 weeks postpartum (2.67 log vs. 3.58 log, P < 0.0001) but not at 6 weeks postpartum (4.49 log vs. 4.40 log, P = 0.79), between single-dose nevirapine/zidovudine + lamivudine and single-dose nevirapine groups, respectively. Nevirapine resistance, measured by population sequencing and sensitive real-time polymerase chain reaction, was significantly less common in those receiving single-dose nevirapine/zidovudine + lamivudine compared with single-dose nevirapine, respectively, at 2 weeks [10% (4 of 40) vs. 74% (31 of 42), P < 0.0001] and 6 weeks postpartum [10% (11 of 115) vs. 64% (41 of 64), P < 0.0001; adjusted relative risk = 0.18, 95% confidence interval (0.10 to 0.34)].

Conclusions: The significant decrease in nevirapine resistance conferred by 1 week of zidovudine + lamivudine should help policymakers optimize peripartum HIV prophylaxis recommendations.

Trial registration: ClinicalTrials.gov NCT00164762.

Figures

Figure 1. Median viral load† and percent…
Figure 1. Median viral load† and percent of women with detectable nevirapine‡ (NVP) by drug regimen among HIV-infected mothers*, Lilongwe, Malawi
*Among women with testable plasma specimens at 2 weeks (sdNVP: n=45; sdNVP/ZDV+3TC: n=53) and 6 weeks postpartum (sdNVP: n=65; sdNVP/ZDV+3TC: n=120); †Chi square p-value for viral load: antenatal: p=0.87; 2 weeks postpartum: p<0.0001, 6 weeks postpartum: p=0.79 ‡Chi square p-value for NVP concentration: delivery: p=0.47; 2 weeks postpartum: p<0.0001; 6 weeks postpartum: p=0.79
Figure 2. Prevalence of NVP resistance mutations…
Figure 2. Prevalence of NVP resistance mutations by drug regimen among HIV-infected mothers*, Lilongwe, Malawi
*Among women with testable plasma specimens at 2 weeks (sdNVP: n=45; sdNVP/ZDV+3TC: n=53) and 6 weeks postpartum (sdNVP: n=65; sdNVP/ZDV+3TC: n=120) and no NVP resistance at an antenatal visit

Source: PubMed

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