Protease sequences from HIV-1 group M subtypes A???H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide

Schatzmayr

Mem. Inst. Oswaldo Cruz

2003

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children

Schatzmayr

Mem. Inst. Oswaldo Cruz

2003

“…Previous data have documented significantly more naturally occurring PI resistance-associated minor (secondary) substitutions that contribute to drug resistance in HIV-1 non-subtype B strains than in subtype B strains collected from patients who have never received PIs (26). Moreover, the patterns of these substitutions were found to be different in subtype B strains compared to those in strains of subtypes A, C, D, F, G, and H and CRF01-AE.…”

mentioning

confidence: 95%

Human Immunodeficiency Virus Type 1 Group M Protease in Cameroon: Genetic Diversity and Protease Inhibitor Mutational Features

Fonjungo¹,

Mpoudi²,

Torimiro³

et al. 2002

J Clin Microbiol

Self Cite

To establish a baseline for monitoring resistance to protease inhibitors (PIs) and examining the efficacy of their use among persons in Cameroon infected with human immunodeficiency virus type 1 (HIV-1), we analyzed genetic variability and PI resistance-associated substitutions in PCR-amplified protease (PR) sequences in strains isolated from 110 HIV-1-infected, drug-naïve Cameroonians. Of the 110 strains, 85 were classified into six HIV-1 PR subtypes, A (n ‫؍‬ 1), B (n ‫؍‬ 1), F (n ‫؍‬ 4), G (n ‫؍‬ 7), H (n ‫؍‬ 1), and J (n ‫؍‬ 7), and a circulating recombinant form, CRF02-AG (n ‫؍‬ 64). PR genes from the remaining 25 (23%) specimens were unclassifiable, whereas 2% (7 of 301) unclassifiable PR sequences were reported for a global collection. Two major PI resistance-associated mutations, 20M and 24I, were detected in strains from only two specimens, whereas secondary mutations were found in strains from all samples except one strain of subtype B and two strains of CRF02-AG. The secondary mutations showed the typical PI resistance-associated pattern for non-subtype B viruses in both classifiable and unclassifiable PR genes, with 36I being the predominant (99%) mutation, followed by 63P (18%), 20R (15%), 77I (13%), and 10I or 10V (11%). Of these mutations, dual and triple PI resistance-associated substitutions were found in 38% of all the Cameroonian strains. Compared with classifiable PR sequences, unclassifiable sequences had significantly more dual and triple substitutions (64% versus 30%; P ‫؍‬ 0.004). Phenotypic and clinical evaluations are needed to estimate whether PI resistance during antiretroviral drug treatment occurs more rapidly in individuals infected with HIV-1 strains harboring multiple PI resistance-associated substitutions. This information may be important for determination of appropriate drug therapies for HIV-1-infected persons in Cameroon, where more than one-third of HIV-1 strains were found to carry dual and triple minor PI resistance-associated mutations.

“…With an increase in prevalence of non-B HIV-1 subtypes in the United States and the availability of antiretroviral drugs in regions of the world where HIV-1 infections other than those of subtype B are prevalent, research on the drug resistance patterns in non-B HIV-1 subtypes and the clinical monitoring of patients having non-B HIV-1 infections is becoming increasingly important (1,9,10,17,19,21). The global deployment of U.S. military personnel has increased the incidence of infections with non-B HIV-1 subtypes in military personnel, further underscoring the need for HIV-1 resistance genotyping tests that work reliably with diverse HIV-1 subtypes (1,2,6,8,12,16,(17)(18)(19). This study assesses the ability of Visible Genetics TRUGENE HIV-1 genotyping test and Applied Biosystems ViroSeq HIV-1 genotyping system to successfully amplify HIV-1 viral RNA and produce DNA sequences for non-B HIV-1 subtypes.…”

mentioning

confidence: 99%

Performance Characteristics of Human Immunodeficiency Virus Type 1 (HIV-1) Genotyping Systems in Sequence-Based Analysis of Subtypes Other than HIV-1 Subtype B

et al. 2003

Given the diversity of human immunodeficiency virus type 1 (HIV-1) subtypes and the emergence of subtypes other than HIV-1 subtype B in the United States, genotypic assays must be capable of delivering sequence data on diverse HIV-1 subtypes. We evaluated the performance of Visible Genetics TRUGENE HIV-1 genotyping kit and Applied Biosystems ViroSeq HIV-1 genotyping system on a panel of 34 well-characterized HIV-1 viral stocks (subtypes A through H). Both assays perform well on diverse HIV-1 subtypes despite being designed for HIV-1 subtype B. The TRUGENE assay produced sequence data for 31 isolates but not for one C and two G isolates. The TRUGENE assay using prototype 1.5 RT-PCR primers and the ViroSeq assay were both successful for all variants tested, although five isolates lacked double-strand sequence coverage in the ViroSeq assay. The availability of standardized HIV-1 genotyping kits that perform reliably with all HIV subtypes will facilitate broad implementation of HIV-1 resistance testing.