Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons

Garcı́a-Lerma, J. Gerardo; Nidtha, Soumya; Blumoff, K; Weinstock, Hillard; Heneine, Walid

doi:10.1073/pnas.241300698

Cited by 117 publications

(103 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another individual recently infected with a drug-resistant isolate containing M41L and a mixture of T215Y/T215D/ T215S, T215D and T215S were estimated to be 10 to 25% and 1% more fit, respectively, than T215Y (71). The improved fitness of the T215D/T215S mutants relative to T215Y was also observed in another study of site-directed mutants (66).…”

Section: Mutations Conferring Resistance To Reversesupporting

confidence: 63%

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

Dykes

Demeter

2007

Clin Microbiol Rev

View full text Add to dashboard Cite

SUMMARY The relative fitness of a variant, according to population genetics theory, is that variant's relative contribution to successive generations. Most drug-resistant human immunodeficiency virus type 1 (HIV-1) variants have reduced replication fitness, but at least some of these deficits can be compensated for by the accumulation of second-site mutations. HIV-1 replication fitness also appears to influence the likelihood of a drug-resistant mutant emerging during treatment failure and is postulated to influence clinical outcomes. A variety of assays are available to measure HIV-1 replication fitness in cell culture; however, there is no agreement regarding which assays best correlate with clinical outcomes. A major limitation is that there is no high-throughput assay that incorporates an internal reference strain as a control and utilizes intact virus isolates. Some retrospective studies have demonstrated statistically significant correlations between HIV-1 replication fitness and clinical outcomes in some patient populations. However, different studies disagree as to which clinical outcomes are most closely associated with fitness. This may be in part due to assay design, sample size limitations, and differences in patient populations. In addition, the strength of the correlations between fitness and clinical outcomes is modest, suggesting that, at present, it would be difficult to utilize these assays for clinical management.

show abstract

Section: Mutations Conferring Resistance To Reversesupporting

confidence: 63%

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

Dykes

Demeter

2007

Clin Microbiol Rev

View full text Add to dashboard Cite

show abstract

“…4,6 In the RT gene, we analyzed the NNRTI mutations A98G, L100I, K101E/P, K103N/ S, V106A/M, V108I, V179D/E, Y181C/I/V, Y188C/H/L, G190A/C/E/S/Q, P225H, F227L, M230L, P236L, and K238N/T and the NRTI mutations M41L, A62V, K65R, D67N/G, D67del, T69D, T69ins, K70E/R, L74V, V75A/M/T, Y115F, Q151M, M184I/V, L210W, T215Y/F, and K219E/ Q/R; this list also includes the mutations 215C//D/E/I/ S/V that are considered revertant forms of 215F/Y. 7 The NRTI mutations (E44D, F116Y, and V118I) in the RT gene and the PI mutations (I13V, G16E, K20I/M/R/T/V, L33I/V, E34Q, E35G, M36I/L/T/V, F53L/Y, Q58E, D60E, I62V, L63P, I64L/M/V, H69K, A71I/L/T/V, T74A/P/S, V77I, V82I, N83D, I85V, N88T, L89V, and I93L/M) in the PR gene were not counted in calculating the prevalence of resistance because they confer resistance only when they occur in combination with other NRTI and PI resistance mutations, respectively. The analyzed plasma samples were 79 for RT sequences and 80 for PR sequences.…”

mentioning

confidence: 99%

Short Communication:Characterization of Drug-Resistance Mutations in HIV Type 1 Isolates from Drug-Naive and ARV-Treated Patients in Bulgaria

Santoro

Ciccozzi

Alteri

et al. 2008

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

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 ϭ 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 ϭ 0.08]. Two (9.1%) naive patients and 40 (70.1%) drugexperienced 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. 1133

show abstract

“…Continued replication in the presence of drug will select for even greater levels of resistance and typically leads to cross-resistance to drugs of the same class (17,39). Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs may compromise the efficacy of drug therapy (10).…”

mentioning

confidence: 99%

Combination of Drugs and Drug-Resistant Reverse Transcriptase Results in a Multiplicative Increase of Human Immunodeficiency Virus Type 1 Mutant Frequencies

Mansky

Pearl

Gajary

2002

J Virol

View full text Add to dashboard Cite

Replication of drug-resistant human immunodeficiency virus type 1 (HIV-1) in the presence of drug can lead to the failure of antiretroviral drug treatment. Drug failure is associated with the accumulation of drug resistance mutations. Previous studies have shown that 3-azido-3-deoxythymidine (AZT), (؊)2,3-dideoxy-3-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can increase the virus in vivo mutation rate. In this study, the combined effects of drug-resistant RT and antiretroviral drugs on the HIV-1 mutant frequency were determined. In most cases, a multiplicative effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT, 3TC, hydroxyurea, and thymidine) and led to increases in the odds of recovering virus mutants to over 20 times that of the HIV-1 mutant frequency in the absence of drug or drug-resistance mutations. This observation indicates that HIV-1 can mutate at a significantly higher rate when drug-resistant virus replicates in the presence of drug. These increased mutant frequencies could have important implications for HIV-1 population dynamics and drug therapy regimens.

show abstract

Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons

Cited by 117 publications

References 30 publications

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

Short Communication:Characterization of Drug-Resistance Mutations in HIV Type 1 Isolates from Drug-Naive and ARV-Treated Patients in Bulgaria

Combination of Drugs and Drug-Resistant Reverse Transcriptase Results in a Multiplicative Increase of Human Immunodeficiency Virus Type 1 Mutant Frequencies

Contact Info

Product

Resources

About