Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.16 (HIV-1 protease)
 2,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To detect and characterize polymerase gene (pol) polymorphisms and mutation patterns in HIV-1C-infected Batswana patients treated with reverse transcriptase inhibitors, samples from AIDS patients treated with highly active antiretroviral therapy (HAART) were sequenced for the region encompassing the entire HIV-1 protease (PR) and the first 335 amino acids of reverse transcriptase (RT). Amongst the 16 patients treated with antiretroviral (ARV) drugs, eight started HAART regimens containing didanosine, stavudine and nevirapine (ddI/d4T/NVP) or efavirenz (EFV) (arm A) while the others started with zidovudine (AZT) and lamivudine (3TC) given together as combivir (CBV) with either NVP or EFV as arm B. Arm B is the first line regimen currently provided by the Botswana ARV national programme. Greater efficacy, in terms of treatment duration, was observed in patients in arm B (14 months) as compared with patients in arm A (9 months); P<0.05, n=8. Appearance of the M184V mutation in the arm B patients coincided with a rebound of viral load (VL) (4.3 +/-0.1 log10 RNA copies/ml) and a significantly improved immunological parameter (deltaCD4=207.0+/-48.1 cells/microl; P<0.05). Interestingly, patients developing the M184V mutation preferentially harboured polymorphisms Q174K and/or I178L located in close proximity to pol position 184. The M184V mutation occurred following a clear clinical benefit consisting of increased CD4 cell counts and lower plasma viral loads. Primary mutations known to be associated with NNRTI and NRTI resistance for HIV-1B were observed in 10 of the 16 treated patients.
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PMID:Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C-infected African patients. 1545 80

Unique viral variants and resistance mutations may occur in the genital tract of HIV-2 ARV-naive infected women. We sequenced and phylogenetically analyzed protease (PR), reverse transcriptase (RT), and envelope (ENV) from PBMC and genital tract samples from four ARV-naive women in Senegal. HIV-2 protease polymorphisms that predict HIV-1 protease inhibitor (PI) resistance were common. Two subjects had protease mutations (T77I and I64V) in genital tract samples that were not found in PBMCs. One subject had the HIV-2 reverse transcriptase M184I mutation in CVL DNA (but not PBMCs) that is known to confer 3TC/FTC resistance in HIV-2. In another subject, the reverse transcriptase A62V mutation was also found in CVL-RNA but not PBMCs. We found no significant difference in ENV variants between PBMCs and the genital tract. HIV-2 RT and PR mutations in the genital tract of ARV-naive females may have implications for transmitted HIV-2 resistance and ARV therapy.
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PMID:HIV type 2 protease, reverse transcriptase, and envelope viral variation in the PBMC and genital tract of ARV-naive women in Senegal. 1854 24

Genotyping reveal emergence of drug resistance (DR)-related mutations in HIV-1 protease (PR) gene in the first-line treatment failure patients as per Stanford DR database. In order to have a subtype C specific prediction model, a three dimensional structure of local wild type C variant is created and the identified mutations were introduced to assess the mutational effects on protease inhibitors (PI) in a homology model. We estimated viral load, CD4 count and conducted DR genotyping in HIV isolates from 129 therapy naive and 20 first-line treatment failure individuals. Several genotypic variations, as compared to subtype B sequence in the Stanford gene database were detected in HIV-1 subtype C isolates from treatment naive individuals. Among these, nine mutations (12S, 15V, 19I, 36I, 41K, 63P, 69K, 89M, 93L) occurred in more than 60% of the isolates and were considered as local wild type for molecular modelling studies. No major mutations were seen in the PR sequences in isolates from treatment-naive individuals, although isolates from two patients had T74S mutation, known to be associated with reduced susceptibility to nelfinavir (NFV) and a combination of M36I, H69K and L89M mutations found in isolates from 77 patients (59.7%), considered to be conferring resistance to tipranavir (TPV) according to ANRS algorithm. Among the first-line treatment failures, an isolate from one patient showed L33F, I47T, M46G, and G48E mutations conferring intermediate resistance to saquinavir (SQV) and lopinavir (LPV). Though the docking energy scores are in agreement with this interpretation for SQV, it, however, indicated these mutations to be causing intermediate to high level resistance to atazanavir (ATV) and tipranavir (TPV) but making it susceptible to LPV. The patient finally responded to a second-line regimen containing 3TC, AZT and LPV with significant viral suppression. All the DR genotyping studies analyse the results using available databases which are all based on subtype B specific sequences. The proposed homology model in this study is unique, as it may predict subtype C specific susceptibility criteria for the available PIs.
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PMID:Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from ART naive and first-line treatment failures in North India using genotypic and docking analysis. 2187 19