Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.
<h4>Background</h4>Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) o...
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Public Library of Science (PLoS)
2009-01-01
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| author | Anitha Moorthy Amita Gupta Ramesh Bhosale Srikanth Tripathy Jayagowri Sastry Smita Kulkarni Madhuri Thakar Renu Bharadwaj Anju Kagal Arvind V Bhore Sandesh Patil Vandana Kulkarni Varadharajan Venkataramani Usha Balasubramaniam Nishi Suryavanshi Carrie Ziemniak Nikhil Gupte Robert Bollinger Deborah Persaud |
| author_facet | Anitha Moorthy Amita Gupta Ramesh Bhosale Srikanth Tripathy Jayagowri Sastry Smita Kulkarni Madhuri Thakar Renu Bharadwaj Anju Kagal Arvind V Bhore Sandesh Patil Vandana Kulkarni Varadharajan Venkataramani Usha Balasubramaniam Nishi Suryavanshi Carrie Ziemniak Nikhil Gupte Robert Bollinger Deborah Persaud |
| author_sort | Anitha Moorthy |
| collection | DOAJ |
| description | <h4>Background</h4>Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.<h4>Methods/findings</h4>Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.<h4>Conclusions/significance</h4>Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.<h4>Trial registration</h4>ClinicalTrials.gov NCT00061321. |
| format | Article |
| id | doaj-art-372edef596d84d8e929a438ed6608388 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-372edef596d84d8e929a438ed66083882025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e409610.1371/journal.pone.0004096Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.Anitha MoorthyAmita GuptaRamesh BhosaleSrikanth TripathyJayagowri SastrySmita KulkarniMadhuri ThakarRenu BharadwajAnju KagalArvind V BhoreSandesh PatilVandana KulkarniVaradharajan VenkataramaniUsha BalasubramaniamNishi SuryavanshiCarrie ZiemniakNikhil GupteRobert BollingerDeborah Persaud<h4>Background</h4>Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.<h4>Methods/findings</h4>Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.<h4>Conclusions/significance</h4>Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.<h4>Trial registration</h4>ClinicalTrials.gov NCT00061321.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004096&type=printable |
| spellingShingle | Anitha Moorthy Amita Gupta Ramesh Bhosale Srikanth Tripathy Jayagowri Sastry Smita Kulkarni Madhuri Thakar Renu Bharadwaj Anju Kagal Arvind V Bhore Sandesh Patil Vandana Kulkarni Varadharajan Venkataramani Usha Balasubramaniam Nishi Suryavanshi Carrie Ziemniak Nikhil Gupte Robert Bollinger Deborah Persaud Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS ONE |
| title | Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. |
| title_full | Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. |
| title_fullStr | Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. |
| title_full_unstemmed | Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. |
| title_short | Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. |
| title_sort | nevirapine resistance and breast milk hiv transmission effects of single and extended dose nevirapine prophylaxis in subtype c hiv infected infants |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004096&type=printable |
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