Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy

Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations

“…It has been shown by several groups that D30N is selected at higher rates in subtype B than in other subtypes under NFV exposure. Non-B subtypes, including subtype C, rarely develop D30N [9][10][11][12], but do select for L90 M, a mutation conferring low-level cross-resistance to several PI [42]. Possible explanations for the low occurrence of D30N in subtype C are related to a more drastic impact on viral fitness [13].…”

“…It confers reduced susceptibility of viruses to that drug per se, constituting a well established primary resistance mutation. Previous studies conducted in patients infected with distinct HIV-1 non-B subtypes have shown that these patients rarely develop the mutation compared with patients infected with subtype B [9][10][11][12]. The low frequency of D30N in subtype C has been associated with a more dramatic reduction in viral replicative capacity (RC) compared with subtype B counterparts carrying the same mutation [13].…”

“…The low frequency of D30N in subtype C has been associated with a more dramatic reduction in viral replicative capacity (RC) compared with subtype B counterparts carrying the same mutation [13]. Moreover, the occurrence of D30N in subtype C has been strongly associated with the compensatory mutations N88D and N83T in vivo and in vitro, respectively [12,13]. However, the structural hindrances governing the differences in replicative fitness and the requirement for those compensatory mutations are yet to be determined.…”

Integrating HIV-1 Pharmacogenomics into the Universal Coverage Health- Care System in Thailand: From Scientific Evidence to Policy

“…Since then, drug resistance rates have been increased [75][76][77][78]. Consequently, without good strategies to reduce the cost of medical expenditure, Thailand would soon face an additional financial burden on their universal health-care coverage system.…”

Differential Evolution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Genes Between HAART-Failing and Naive- Treated Individuals

“…However, the activity of antiretroviral (ARV) drugs and host immune system create an environment that positively selects mutations that permit HIV-1 to replicate and perhaps compensate deleterious mutations in essential functional regions in the viral genome [10,11], partially reestablishing *Address correspondence to this author at the Laboratório de Infectologia e Parasitologia Molecular (LIPAM), Hospital Universitário Clementino Fraga Filho, Rua Professor Rodolpho Paulo Rocco, nº 255, Cidade Universitária -Ilha do Fundão -RJ, Brazil; Tel: 55 21 25622617; E-mail: rafael_varella@hotmail.com viral fitness [12]. Resistance to ARV drugs frequently involves mutations in well characterized sites of HIV-1 protease (PR) and reverse transcriptase (RT) genes [13], which are related to fundamental enzymatic functions [14,15].…”