OBJECTIVE: To analyze the genotypic resistance profiles of HIV-infected children from rural China who were experiencing virologic failure to first-line antiretroviral therapy regimens and to evaluate 1-year regimen efficacy after switching to second-line therapy. METHODS: A prospective cohort study was performed. Seventy-six children from the first rural pilot program with HIV viral load >1000 copies per milliliter on 2 consecutive occasions were studied. We analyzed genotype results and observed second-line therapy efficacy to 12 months. RESULTS: After 33.1 (23.3, 41.1) months on first-line treatment after enrollment into national program, 98.7% of genotyped patients developed high-level resistance to nevirapine and 81.6% of patients had high-level resistance to efavirenz. High-level resistance to lamivudine was observed in 82.9%, followed by 57.9% for stavudine and 52.6% for zidovudine. In the nonnucleoside reverse transcriptase inhibitor class, the most common mutations were K103N/S at 50% and Y181C/I at 48.7%. M184V/I was the most common nucleoside reverse transcriptase inhibitor resistance mutation at 77.6%, the mutation rate for ≥3 thymidine analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. After 12 months of boosted protease inhibitor-based second-line therapy, CD4 counts had on average increased 256 cells per cubic millimeter compared with switch baseline and 83.1% of patients had undetectable viral loads (<50 copies/mL). CONCLUSIONS: HIV-1-infected children who continued their first-line regimen regardless of virologic failure harbored multiple resistance mutations. Although the extent of resistance to nucleoside reverse transcriptase inhibitor class drugs would be expected to limit subsequent treatment options, the current second-line regimen remained effective during a 1-year observational period.
OBJECTIVE: To analyze the genotypic resistance profiles of HIV-infectedchildren from rural China who were experiencing virologic failure to first-line antiretroviral therapy regimens and to evaluate 1-year regimen efficacy after switching to second-line therapy. METHODS: A prospective cohort study was performed. Seventy-six children from the first rural pilot program with HIV viral load >1000 copies per milliliter on 2 consecutive occasions were studied. We analyzed genotype results and observed second-line therapy efficacy to 12 months. RESULTS: After 33.1 (23.3, 41.1) months on first-line treatment after enrollment into national program, 98.7% of genotyped patients developed high-level resistance to nevirapine and 81.6% of patients had high-level resistance to efavirenz. High-level resistance to lamivudine was observed in 82.9%, followed by 57.9% for stavudine and 52.6% for zidovudine. In the nonnucleoside reverse transcriptase inhibitor class, the most common mutations were K103N/S at 50% and Y181C/I at 48.7%. M184V/I was the most common nucleoside reverse transcriptase inhibitor resistance mutation at 77.6%, the mutation rate for ≥3 thymidine analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. After 12 months of boosted protease inhibitor-based second-line therapy, CD4 counts had on average increased 256 cells per cubic millimeter compared with switch baseline and 83.1% of patients had undetectable viral loads (<50 copies/mL). CONCLUSIONS:HIV-1-infectedchildren who continued their first-line regimen regardless of virologic failure harbored multiple resistance mutations. Although the extent of resistance to nucleoside reverse transcriptase inhibitor class drugs would be expected to limit subsequent treatment options, the current second-line regimen remained effective during a 1-year observational period.
Authors: Benjamin P Westley; Allison K DeLong; Chhraing S Tray; Dim Sophearin; Elizabeth M Dufort; Eric Nerrienet; Leeann Schreier; Joseph I Harwell; Rami Kantor Journal: Clin Infect Dis Date: 2012-04-26 Impact factor: 9.079
Authors: Awachana Jiamsakul; Azar Kariminia; Keri N Althoff; Carina Cesar; Claudia P Cortes; Mary-Ann Davies; Viet Chau Do; Brian Eley; John Gill; Nagalingeswaran Kumarasamy; Daisy Maria Machado; Richard Moore; Hans Prozesky; Elizabeth Zaniewski; Matthew Law Journal: J Acquir Immune Defic Syndr Date: 2017-11-01 Impact factor: 3.731
Authors: Rashida A Ferrand; Datonye Briggs; Jane Ferguson; Martina Penazzato; Alice Armstrong; Peter MacPherson; David A Ross; Katharina Kranzer Journal: Trop Med Int Health Date: 2016-01-10 Impact factor: 2.622