Incidence and impact of resistance against approved antiretroviral drugs

Abstract

More than 15 antiretroviral drugs are now available for clinical use, and have led to signi®cant reductions in morbidity and mortality for HIV infected individuals. Nevertheless, antiviral drug resistance emerges to all these drugs, which limits their bene®t. This review addresses the biological basis of antiretroviral drug resistance, and the prevalence of speci®c drug resistance associated mutations in patients treated with the three currently available classes of agents, namely nucleoside analogue reverse transcriptase inhibitors, non nucleoside reverse transcriptase inhibitors and protease inhibitors. In addition, data on prevalence of HIV drug resistance in untreated individuals published to date are summarised, and the implications of potential transmission of drug resistant HIV is discussed.

Transmission of HIV-1 drug resistance

“…(NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (Pillay et al, 2000). Resistance-associated mutations in the viral reverse-transcriptase (RT) and protease (P) genes are classed as primary if their presence alone confers resistance to a particular drug.…”

Conflicting interpretations of the prevalence of mutations associated with drug resistance in antiviral naı̈ve HIV-1 patients with acute and chronic infection

“…On the other hand, some mutations were correlated to possible resistance against reverse transcriptase inhibitors in two never treated patients with long-lasting infection. In the absence of drug selection, the wild type virus did not re-emerge as expected though several published reports suggested that, in the absence of drug selection, mutations initially present might revert over time to wild type because of its better replicative capacity [4,14,18,[26][27][28][29].…”

“…In addition, several codon substitutions not correlated to key mutations and probably occurring as spontaneous genetic polymorphisms [18,30,31], were detected in several patients belonging to both groups. The overall frequency of secondary mutations in the protease gene was significantly greater than that observed in reverse transcriptase, probably due to the polymorphic nature of the protease gene that may lead to a heterogeneous response to protease inhibitors.…”

“…Sequences were aligned and compared with a lymphadenopathy-associated virus type 1 (HIV-B-LAV1) consensus sequence using Visible Genetics Librarian software. We focused on mutations at positions in the pol gene known to be associated with the most commonly used drugs against HIV-1 [18,[21][22][23].…”

“…In particular, several cross-sectional surveys to detect primary infection involving drug resistant virus have shown a variable prevalence (ranging from 0 to 10%) of primary mutations conferring resistance to reverse transcriptase and protease inhibitors [9,10,12,17] . The detection of drug resistant virus in patients with established HIV infection before starting therapy, might have a highly positive impact on the choice and outcome of therapy even though factors such as viral load and CD4+ T cell count had been taken into account [2,[18][19][20].…”