Abstract
Background. The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. Methods. We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4+ T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. Results. Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4 + T cell latent reservoir in all 5 infants. Conclusions. The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1402-1410 |
| Number of pages | 9 |
| Journal | Journal of Infectious Diseases |
| Volume | 195 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2007 |
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ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Immunology
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Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. / Persaud, Deborah; Palumbo, Paul; Ziemniak, Carrie; Chen, Jie; Ray, Stuart Campbell; Hughes, Michael; Havens, Peter; Purswani, Murli; Gaur, Aditya H.; Chadwick, Ellen Gould.
In: Journal of Infectious Diseases, Vol. 195, No. 10, 15.05.2007, p. 1402-1410.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States
AU - Persaud, Deborah
AU - Palumbo, Paul
AU - Ziemniak, Carrie
AU - Chen, Jie
AU - Ray, Stuart Campbell
AU - Hughes, Michael
AU - Havens, Peter
AU - Purswani, Murli
AU - Gaur, Aditya H.
AU - Chadwick, Ellen Gould
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Background. The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. Methods. We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4+ T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. Results. Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4 + T cell latent reservoir in all 5 infants. Conclusions. The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.
AB - Background. The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. Methods. We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4+ T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. Results. Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4 + T cell latent reservoir in all 5 infants. Conclusions. The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.
UR - http://www.scopus.com/inward/record.url?scp=34248165997&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248165997&partnerID=8YFLogxK
U2 - 10.1086/513871
DO - 10.1086/513871
M3 - Article
C2 - 17436219
AN - SCOPUS:34248165997
VL - 195
SP - 1402
EP - 1410
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 10
ER -