literature

HIV mutation literature information.

Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance.

PMID: 19812032 2009 The Journal of biological chemistry

Conclusion: Biochemical and structural data have elucidated two distinct mechanisms of NRTI resistance of 1) discrimination due to steric hindrance by M184V/I mutation to 3TC-TP and emtricitabine-TP and 2) the ATP-mediated excision of incorporated NRTIs exemplified by the TAMs, which is the primary mechanism of resistance to AZT.

RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy.

PMID: 19889213 2009 Retrovirology

Figure: Horizontal red bars show the percentage of all subpopulations with drug resistant mutations (K65R, K103N, M184I, and M184V) in the population of each week.

Discussion: By contrast, the outgrowth of a single clonal subpopulation resistant to both EFV and FTC that resulted in therapeutic failure implies that the K103N population may have been so small that the M184I variant was present at a low frequency at the time of initiation of combination therapy.

Discussion: This animal subsequently failed combination therapy, at which time the virus population was characterized by the appearance of viruses with additional mutations, initially K65R (conferring TNF resistance) followed by a clonal subpopulation containing

PMID: 19911963 2009 Clinical infectious diseases

Method: Bar graphs were used to display the accumulation of mutations (any NNRTI, M184V/I, or any TAM) at detection of viremia and at 6, 12, and 18 months of persistent viremia on first-line cART for patients with multiple resistance tests at least one of which was >=12 months after first detection of viremia.

Method: Logistic regression was used to identify variables associated with the presence of i) NNRTI resistance and ii) the M184V/I mutation at first detection of viremia and to evaluate associations with resuppression within 6 months of detecting viremia among subjects with an HIV RNA result within this time frame.

Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure.

PMID: 19949656 2009 Journal of Korean medical science

Abstract: M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%).

Result: M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (17/41, 41.5%) and M46I/L (14/41, 34.2%).

Discussion: Almost all patients were taking 3TC in our study group and most isolates of these patients revealed resistance to 3TC associated with M184V/I mutation.

The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications.

PMID: 20190870 2009 HIV therapy

Introduction: The rapid selection of K65K/R and M184M/I/V as minority species emerging on separate clones underestimated resistance to TDF, ABC and ddI in phenotypic assays.

Introduction: The replicative compromise conferred by K65R is reflected by the strong selective pressure driving its rate of disappearance/reversion upon treatment interruption - K65R (1 month) > M184I/V (3 months) > TAMs (4-6 months) and Q151-NAMs (5.6 months).

Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage.

PMID: 18218633 2008 The Journal of biological chemistry

Abstract: Finally, we compared the binary complex structures of wild-type and M184I RTs.

Abstract: First, unlike variants with wild-type M184, M184I RT variants displayed significantly reduced DNA polymerase activity at low dNTP concentrations, which is indicative of reduced dNTP binding affinity.

Abstract: Second, the M184I variant displayed a approximately 10- to 13-fold reduction in dNTP binding affinity, compared with the Met-184 variant.

Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect.

PMID: 18218634 2008 The Journal of biological chemistry

Abstract: In this study, we show that the altered properties of the M184I and M184A RT mutants that we have measured, including decreased processivity, a slower rate of primer extension, and increased strand transfer activity, can all be explained by a defect in dNTP utilization.

Abstract: The 2',3'-dideoxy-3'-thiacytidine drug-resistant M184I HIV-1 reverse transcriptase (RT) has been shown to synthesize DNA with decreased processivity compared with the wild-type RT.

Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece.

PMID: 18275347 2008 AIDS research and human retroviruses

Abstract: The most frequent ARMs of each drug category were to NRTIs at codons M184V [present in 149 tests (63.6%)], M41L [79 (33.8%)], K70R [66 (28.2%)], M184VI [58 (24.8%)], T215YF [53 (22.7%)], D67N [82 (35.0%)], T215Y [72 (30.8%)], K219Q [47 (20.1%)], K219E/Q [54 (23.1%)], and L210W [49 (20.9%)], respectively.

Entecavir exhibits inhibitory activity against human immunodeficiency virus under conditions of reduced viral challenge.

PMID: 18316521 2008 Antimicrobial agents and chemotherapy

Abstract: Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus.

Short communication: the number of HIV major NRTI mutations correlates directly with other antiretroviral-associated mutations and indirectly with replicative capacity and reduced drug susceptibility.

PMID: 18366310 2008 AIDS research and human retroviruses

Abstract: RC declined from a mean of 97.8% for samples without NRTI-DRMs to 68.9% with one NRTI-DRM, possibly due to reduced fitness conferred by K65R or M184I/V, to an RC of 43.9% for samples with seven to eight NRTI-DRMs.

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