Dataset Information

Characterization of drug-resistance mutations in HIV type 1 isolates from drug-naive and ARV-treated patients in Bulgaria.

ABSTRACT: Little information is available about the prevalence of resistance mutations to reverse transcriptase (RT) and protease (PR) inhibitors of HIV-1, after the introduction of antiretroviral treatment in Bulgaria. To fill this gap, we analyzed 80 plasma samples from HIV-1-infected Bulgarian patients, 22 naive at antiretroviral treatment (ARV) and 58 ARV experienced. The subtypes B and A resulted in the two most prevalent (41 patients and 18 patients, respectively). The proportion of subtype B among naive and treated patients was similar in each group (57% vs. 47%, p = 0.62), while a major proportion of subtypes A was present in drug-naive patients rather than in treated patients [8/22 (36.4%) vs. 10/58 (17.2%), p = 0.08]. Two (9.1%) naive patients and 40 (70.1%) drug-experienced patients had viruses carrying at least one mutation conferring resistance to ARV drugs. Of 57 patients having experience with nucleoside reverse transcriptase inhibitors (NRTI), 32 (56.1%) had NRTI resistance mutations; 8/14 (57.2%) patients having experience with non-NRTI (NNRTI) had viruses carrying NNRTI resistance mutations; and 21/46 (45.7%) patients having experience with protease inhibitors (PI) had PI resistance mutations. The commonest resistance mutations resulted in the NRTI mutation M184V (42.1%) and the PI mutation L90M (24.1%). In conclusion, due to the detection of the substantial transmission of resistant variants to newly infected individuals, continuous surveillance is required, since greater access to highly active antiretroviral therapy (HAART) will be expected in Bulgaria. Furthermore, surveillance of PR and RT sequences is also convenient to monitor the introduction of nonsubtype B HIV-1 strains in Bulgaria.

SUBMITTER: Santoro MM

PROVIDER: S-EPMC2928031 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Characterization of drug-resistance mutations in HIV type 1 isolates from drug-naive and ARV-treated patients in Bulgaria.

Santoro Maria Mercedes MM Ciccozzi Massimo M Alteri Claudia C Montieri Stefania S Alexiev Ivailo I Dimova Iordanka I Ceccherini-Silberstein Francesca F Beshkov Danail D Rezza Giovanni G Perno Carlo Federico CF

AIDS research and human retroviruses 20080901 9

Little information is available about the prevalence of resistance mutations to reverse transcriptase (RT) and protease (PR) inhibitors of HIV-1, after the introduction of antiretroviral treatment in Bulgaria. To fill this gap, we analyzed 80 plasma samples from HIV-1-infected Bulgarian patients, 22 naive at antiretroviral treatment (ARV) and 58 ARV experienced. The subtypes B and A resulted in the two most prevalent (41 patients and 18 patients, respectively). The proportion of subtype B among ...[more]

PMID: 18788909

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Project description:ObjectivesSurveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs.DesignThis is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients.MethodsThe prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility.ResultsPrevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90?M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads.ConclusionThe significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.

Project description:BACKGROUND:Access to antiretroviral therapy (ART) has increased dramatically in Sub-Saharan Africa. In Kenya, 560,000 people had access to ART by the end of 2011. This scaling up of ART has raised challenges to the Kenyan health system due to emergence of drug resistant viruses among those on treatment and possible onward transmission. To counter this, and come up with an effective treatment strategy, it has become vital to determine baseline mutations associated with drug resistance among the circulating strains of HIV-1 in Kenya. METHODS:The prevalence of mutations associated with drug resistance in HIV-1 protease (PR) and reverse transcriptase (RT) regions from 188 HIV-1 infected treatment-naïve pregnant women was investigated in Kapsabet, Nandi Hills and Kitale district hospitals of Kenya. Blood samples were collected between April 2005 and June 2006. The HIV-1 pol gene was amplified using primers for HIV-1 PR and RT and sequenced using the BigDye chemistry. The mutations were analyzed based on the IAS algorithm as well as the Stanford University HIV Drug Resistance Database. RESULTS:Based on the PR and RT sequences, HIV-1 subtypes A1 (n=117, 62.2%), A2 (n=2, 1.1%), D (n=27, 14.4%), C (n=13, 6.9%), G (n=3, 1.6%), and possible recombinants (n=26, 13.8%) were detected. Mutations associated with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside RTI (NNRTI)-resistance were detected in 1.6% (3 of 188) and 1.1% (2 of 188), respectively. Mutations associated with PI resistance were detected in 0.5% (1 of 188) of the study population. CONCLUSION:The prevalence of drug resistance among drug-naïve pregnant women in rural North Rift, Kenya in 2006 was 3.2%. Major drug resistance mutations associated with PIs, NRTIs and NNRTIs do exist among treatment-naïve pregnant women in North Rift, Kenya. There is a need for consistent follow-up of drug-naïve individuals in this region to determine the impact of mutations on treatment outcomes.

Dataset Information

Characterization of drug-resistance mutations in HIV type 1 isolates from drug-naive and ARV-treated patients in Bulgaria.

Publications

Characterization of drug-resistance mutations in HIV type 1 isolates from drug-naive and ARV-treated patients in Bulgaria.

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