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Abstract

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1). Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.

Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria

“…Pol gene polymorphisms usually occur in non-B HIV-1 strains as genetic fingerprints that lowers their susceptibility to ARV compounds [35][36][37]. Other mutations/polymorphisms that occurred at very high frequencies among patients in this study include; I13V/A, K20I, E35Q, M36I/L, R41K, R57K/G, L63T/P/S/Q, C67E/S, H69K/R, V82I and L89M.…”

Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance

“…However, numerous reports have also shown that intersubtype diversity can influence the effectiveness of antiviral therapy [reviewed in (Santos and Soares, 2010)]. Genetic differences between the HIV-1 subtypes can alter the response to certain antiviral drugs, the pathway and speed of acquiring resistance, the drug mutational pattern, the level of drug resistance, and the overall viral replicative capacity (Abecasis et al, 2005; Brenner et al, 2003; Brenner et al, 2006; Caride et al, 2001; Grossman et al, 2004; Holguin et al, 2006; Lai et al, 2010; Martinez-Cajas et al, 2009; Palmer et al, 1998; Soares et al, 2007). Therefore, it is important to understand the emergence of drug resistance in non-B subtypes to develop different drug strategies and better aid those patients not responding to therapy.…”

Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

“…However, fewer data are available on the genetic mechanisms of drug resistance in non-B viruses, and some in vitro and in vivo observations suggest that the various subtypes may respond differently to certain antiretroviral drugs [27,28,29,30,31,32,33,34,35]. …”