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

Abstract

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.

Drug Resistance Mutations in HIV Type 1 Isolates from Patients Failing Antiretroviral Therapy in Morocco

“…28 The analysis of the frequency of DRMs by subtype revealed the global frequency of viral resistance was slightly smaller in patients infected by non-B subtypes; 50% had a resistant virus (6/12, 2 A1, 2 G, 1 C, and 1CRF02_AG) compared to 54% (18/33) for patients infected with a B strain. Mutations conferring resistance to both NRTIs and PIs were more frequently present in non-B subtype (50%) than in B strains (33%), while triple-class resistance was observed in subtype G. Interestingly, the distribution of minor resistance mutations in protease at positions 36, 69, and 89 was observed more frequently in non-B subtype (92%); the reported prevalence is similar to the prevalence reported in other studies, 29,30 This is the first study of HIV-1 resistance mutations in patients failing ARV therapy in Morocco; it will be important to collect more extensive data on resistance mutations in HIV-1 isolates from patients experiencing virological failure while receiving ART, together with surveys of DRMs in naive patients.…”

Response of Simian Immunodeficiency Virus to the Novel Nucleoside Reverse Transcriptase Inhibitor 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine In Vitro and In Vivo

“…Sixty days after the discontinuation of EFdA therapy, however, the rebound virus contained 2 significant changes, conversion of the methionine at position 184 to either valine or isoleucine (M184V and M184I, respectively; 6 of 12 clones). Although these mutations are well known for conferring resistance to other NRTIs (23,25), they did not result in a significant change in virus burden during EFdA therapy. Whether treatment with a higher dose of EFdA or a more prolonged therapy would have had a greater impact on infection and disease will require further study with a larger cohort of animals.…”

“…One potential concern is that EFdA treatment resulted in selection of RT mutations associated with high-level resistance to the widely used NRTIs lamivudine (3TC) and FTC (23,25). This finding might discourage the use of EFdA as a first-line therapy, because it might preclude 3TC and FTC from subsequent use in these patients.…”

“…This finding might discourage the use of EFdA as a first-line therapy, because it might preclude 3TC and FTC from subsequent use in these patients. However, M184I/V mutations are already prevalent in treatment-experienced patients due to the widespread use of both 3TC and FTC in HAART (20,25). Indeed, despite the appearance of M184V/I-containing variants in the rebounded virus after drug was removed, EFdA successfully controlled virus burden to undetectable levels in both blood and tissues throughout the interval of therapy.…”

Screening for and Verification of Novel Mutations Associated with Drug Resistance in the HIV Type 1subtype B′ in China

“…The prevalence of TAMs-I and TAMs-II, for example, was different between CRF02_AG and subtype F, and some differences in the resistance-associated mutations have been found among patients infected with B, C, F, and CRF02_AG subtypes. Mutations at the protease regions such as 20MRI, 36I, and 89IMT are more prevalent among non-B subtypes, but mutations 84V, 10FR, 63P, 71LTV and 77I are common in subtype B [33]. The systemic review on the distinct resistant mutations among HIV-1 was conducted by Martinez-Cajas JL and collaborators in 2009 [34], which indicated formally that the differences among known resistant-associated mutations between the subtype B and the non-B subtypes are marginal because the differences are primarily minor mutations.…”