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Journal of the International AIDS Society

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Open Access 01-12-2009 | Review

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

Authors: Jorge L Martinez-Cajas, Nitika P Pai, Marina B Klein, Mark A Wainberg

Published in: Journal of the International AIDS Society | Issue 1/2009

Abstract

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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Title: Differences in resistance mutations among HIV-1 non-subtype B infections: a systematic review of evidence (1996–2008)
Authors: Jorge L Martinez-Cajas
Nitika P Pai
Marina B Klein
Mark A Wainberg
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Journal of the International AIDS Society / Issue 1/2009
Electronic ISSN: 1758-2652
DOI: https://doi.org/10.1186/1758-2652-12-11

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Other articles of this Issue 1/2009

Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals recently diagnosed with HIV

Transplantation of selected or transgenic blood stem cells – a future treatment for HIV/AIDS?

Long term outcomes of antiretroviral therapy in a large HIV/AIDS care clinic in urban South Africa: a prospective cohort study

Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected patients in Botswana after failure of thymidine analogue-based regimens

Validation of AIDS-related mortality in Botswana

Keynote webinar | Spotlight on medication adherence

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At a glance: The STEP trials