12 research outputs found
Recommended from our members
Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria
Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access
Technology in Massachusetts Schools, 2004-2005
BACKGROUND:ATCC HIV-1 drug resistance test kit was designed to detect HIV-1 drug resistance (HIVDR) mutations in the protease and reverse transcriptase genes for all HIV-1 group M subtypes and circulating recombinant forms. The test has been validated for both plasma and dried blood spot specimen types with viral load (VL) of ≥1000 copies/ml. We performed an in-country assessment on the kit to determine the genotyping sensitivity and its accuracy in detecting HIVDR mutations using plasma samples stored under suboptimal conditions. METHODS:Among 572 samples with VL ≥1000 copies/ml that had been genotyped by ViroSeq assay, 183 were randomly selected, including 85 successful genotyped and 98 unsuccessful genotyped samples. They were tested with ATCC kits following the manufacturer's instructions. Sequence identity and HIVDR patterns were analysed with Stanford University HIV Drug Resistance HIVdb program. RESULTS:Of the 183 samples, 127 (69.4%) were successfully genotyped by either method. While ViroSeq system genotyped 85/183 (46.5%) with median VL of 32,971 (IQR: 11,150-96,506) copies/ml, ATCC genotyped 115/183 (62.8%) samples with median VL of 23,068 (IQR: 7,397-86,086) copies/ml. Of the 98 unsuccessful genotyped samples with ViroSeq assay, 42 (42.9%) samples with lower median VL of 13,906 (IQR: 6,122-72,329) copies/ml were successfully genotyped using ATCC. Sequence identity analysis revealed that the sequences generated by both methods were >98% identical and yielded similar HIVDR profiles at individual patient level. CONCLUSION:This study confirms that ATCC kit showed greater sensitivity in genotyping plasma samples stored in suboptimal conditions experiencing frequent and prolonged power outage. Thus, it is more sensitive particularly for subtypes A and A/G HIV-1 in resource-limited settings
Patient Characteristics by Duration of Second-Line Treatment Failure.
a<p>Time from 2 L initiation, or last suppressed VL on 2 L, to genotype sample.</p>b<p>Numbers represent: Median (IQR) unless otherwise indicated.</p>c<p>Time from 2 L initiation to genotype sample.</p
Characteristics for Patients who Initiated Third-Line ART.
c<p>Results represent median (IQR) except where indicated.</p>d<p>Time from 2 L initiation, or last suppressed VL on 2 L, to genotype sample.</p
Prevalence of reverse transcriptase mutations.
<p>(A) NRTI resistance mutations; thymidine analog mutations (TAMs) are in light grey. (B) NNRTI resistance mutations; minor mutations indicated by light grey.</p
Accumulation of Protease Mutations According to Duration of Second-Line Treatment Failure.
<p>Accumulation of Protease Mutations According to Duration of Second-Line Treatment Failure.</p
HIV-1 Drug Resistance mutations against nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) identified by the ATCC assay versus the ViroSeq assay for those individual patients harbouring drug resistance mutations.
<p>HIV-1 Drug Resistance mutations against nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) identified by the ATCC assay versus the ViroSeq assay for those individual patients harbouring drug resistance mutations.</p
Distribution of genotyped samples by assay used, duration of sample storage and median viral load levels.
<p>Distribution of genotyped samples by assay used, duration of sample storage and median viral load levels.</p
Distribution of HIV-1 subtypes and recombinants in samples with ATCC and viroseq discordant genotyping successes.
<p>Distribution of HIV-1 subtypes and recombinants in samples with ATCC and viroseq discordant genotyping successes.</p