HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment

Tupinambás, Unaí; Aleixo, Agdemir Waléria; Greco, Dirceu Bartolomeu

doi:10.1590/s1413-86702005000400009

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…It has been suggested that when the subtype B virus develops resistance to nelfinavir, it tends to develop mutation 30N, while non-B subtypes (specially C, F, G) are more likely to develop the 90M mutation. 5,31 Our results suggest otherwise. Among the secondary mutations to PIs, 20MIRTLV, 36ILV-TA, and 89IMT were more prevalent in non-B subtypes, while 10FR, 63P, 71ILTV, and 77I were more common in the subtype B virus, data very similar to those described in other studies.…”

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confidence: 47%

Resistance-Associated Mutation Prevalence According to Subtypes B and Non-B of HIV Type 1 in Antiretroviral-Experienced Patients in Minas Gerais, Brazil

Westin

Biscione

Fonseca

et al. 2011

AIDS Research and Human Retroviruses

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The emergence of resistance-associated mutations to the antiretroviral agents and the genetic variability of HIV-1 impose challenges to therapeutic success. We report the results of genotype testing assays performed between 2002 and 2006 in 240 antiretroviral-experienced patients followed up in an HIV reference center in Brazil. Drug resistance mutations and viral subtypes were assessed through the algorithms from the Brazilian Genotyping Network (RENAGENO-Brazil) and from Stanford University. Mutation 184VI was the most prevalent (70%) and the thymidine analogue mutations that appeared most frequently were 215FY, 41L, 67N, and 210W, in this order. Among nonnucleoside reverse transcriptase inhibitor mutations, 103NS (32.5%) stood out. HIV subtype B was identified in 184 patients (76.7%). A significant increasing trend in the prevalence of non-B subtypes was observed during the study period (p=0.004). The main differences in prevalence of mutations among HIV-1 subtypes were related to viral protease, with 20MRI, 36I, and 89IMT more prevalent among non-B subtypes, and 84V, 10FR, 63P, 71LTV, and 77I more common in subtype B (p<0.05). Most mutations to etravirine had a prevalence lower than 10%, but at least one mutation to this drug was observed in 45% of the patients. In only 11 patients (4.6%) three mutations to etravirine were verified. Regional surveillance of the resistance profile and HIV-1 subtypes is crucial in the context of public health, to prevent the transmission of resistant strains and to guide the introduction of new drugs in a specific population.

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confidence: 47%

Resistance-Associated Mutation Prevalence According to Subtypes B and Non-B of HIV Type 1 in Antiretroviral-Experienced Patients in Minas Gerais, Brazil

Westin

Biscione

Fonseca

et al. 2011

AIDS Research and Human Retroviruses

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“…The final 50 study sub-set has been tabulated (Table S2; Additional File 2) [12-61]. Although a vast majority (86%) of the studies were observational, a small proportion (4%) were randomized controlled trials.…”

Section: Resultsmentioning

confidence: 99%

Differences in resistance mutations among HIV‐1 non‐subtype B infections: a systematic review of evidence (1996–2008)

Martínez-Cajas

Pai

Klein

et al. 2009

Journal of the International AIDS Society

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Ninety percent of HIV-1-infected people worldwide harbour non-subtype B variants of HIV-1. Yet knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Although a few reviews, editorials and perspectives have been published alluding to this lack of data among non-B subtypes, no systematic review has been performed to date.With this in mind, we conducted a systematic review (1996–2008) of all published studies performed on the basis of non-subtype B HIV-1 infections treated with antiretroviral drugs that reported genotype resistance tests. Using an established search string, 50 studies were deemed relevant for this review.These studies reported genotyping data from non-B HIV-1 infections that had been treated with either reverse transcriptase inhibitors or protease inhibitors. While most major resistance mutations in subtype B were also found in non-B subtypes, a few novel mutations in non-B subtypes were recognized. The main differences are reflected in the discoveries that: (i) the non-nucleoside reverse transcriptase inhibitor resistance mutation, V106M, has been seen in subtype C and CRF01_AE, but not in subtype B, (ii) the protease inhibitor mutations L89I/V have been reported in C, F and G subtypes, but not in B, (iii) a nelfinavir selected non-D30N containing pathway predominated in CRF01_AE and CRF02_AG, while the emergence of D30N is favoured in subtypes B and D, (iv) studies on thymidine analog-treated subtype C infections from South Africa, Botswana and Malawi have reported a higher frequency of the K65R resistance mutation than that typically seen with subtype B.Additionally, some substitutions that seem to impact non-B viruses differentially are: reverse transcriptase mutations G196E, A98G/S, and V75M; and protease mutations M89I/V and I93L.Polymorphisms that were common in non-B subtypes and that may contribute to resistance tended to persist or become more frequent after drug exposure. Some, but not all, are recognized as minor resistance mutations in B subtypes. These observed differences in resistance pathways may impact cross-resistance and the selection of second-line regimens with protease inhibitors. Attention to newer drug combinations, as well as baseline genotyping of non-B isolates, in well-designed longitudinal studies with long duration of follow up are needed.

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“…Primary mutations such as D30N, V82A, and L90M occur at or close to the active site [64]. D30N is observed in patients receiving nelfinavir [66]. The predominantly mutation at codon 82, V82A/T/F/S, occurs in patients receiving treatment with indinavir and ritonavir [62].…”

Section: Mechanisms Of Resistance To Pismentioning

confidence: 99%

“…This mutation was found in approximately 1% of untreated individuals with subtype B virus and in approximately 5-10% of untreated individuals with non-B subtype virus [65]. D30N is observed in patients receiving nelfinavir [66]. Crossresistance to indinavir, ritonavir, and saquinavir has been observed in isolates that have the combined mutations N88D and L90M.…”

Section: Mechanisms Of Resistance To Pismentioning

confidence: 99%

Mechanism of HIV antiretroviral drugs progress toward drug resistance

Ammaranond

Sanguansittianan

2011

Fundamemntal Clinical Pharma

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The rapid replication rate of HIV-1 RNA and its inherent genetic variation have led to the production of many HIV-1 variants with decreased drug susceptibility. The capacity of HIV to develop drug resistance mutations is a major obstacle to long-term effective anti-HIV therapy. Incomplete suppression of viral replication with an initial drug regimen diminishes the clinical benefit to the patient and may promote the development of broader drug resistance that may cause subsequent treatment regimens to be ineffective. The increased clinical use of combination antiretroviral treatment for HIV-1 infection has led to the selection of viral strains resistant to multiple drugs, including strains resistant to all licensed nucleoside analog RT inhibitors and protease inhibitors. Therefore, it is important to understand the influence of such mutations on viral properties such as replicative fitness, fidelity, and mutation rates. Although research continues to improve our understanding of resistance, leading to refined treatment strategies and, in some cases, improved outcome, resistance to antiretroviral therapy remains a major cause of treatment failure among patients living with HIV-1.

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HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment

Cited by 5 publications

References 15 publications

Resistance-Associated Mutation Prevalence According to Subtypes B and Non-B of HIV Type 1 in Antiretroviral-Experienced Patients in Minas Gerais, Brazil

Resistance-Associated Mutation Prevalence According to Subtypes B and Non-B of HIV Type 1 in Antiretroviral-Experienced Patients in Minas Gerais, Brazil

Differences in resistance mutations among HIV‐1 non‐subtype B infections: a systematic review of evidence (1996–2008)

Mechanism of HIV antiretroviral drugs progress toward drug resistance

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