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

Martinez-Cajas JL, Pai NP, Klein MB, Wainberg MA - J Int AIDS Soc (2009)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada. mark.wainberg@mcgill.ca.

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.

No MeSH data available.


Related in: MedlinePlus

Flow diagramme for study selection.
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Figure 1: Flow diagramme for study selection.

Mentions: The study selection methodology is shown in Figure 1. We searched 11 electronic databases of full-text articles and conference abstracts, i.e., PUBMED (1996–2008), Web of Science (1996–2008), EMBASE (1996–2008), BIOSIS (1996–2008), AIDSLINE (1996–2005), OVID (1996–2008), Psychinfor (1996–2008), Cochrane controlled trials register (1996–2008), DARE (1996–2008), COCHRANE (1996–2008), and ILLUMINA (1996–2007). A total of 5892 references were identified from these 11 databases. After excluding duplicates (the same reference found by two database engines), 3691 citations were considered relevant after the first screen.


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

Martinez-Cajas JL, Pai NP, Klein MB, Wainberg MA - J Int AIDS Soc (2009)

Flow diagramme for study selection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713201&req=5

Figure 1: Flow diagramme for study selection.
Mentions: The study selection methodology is shown in Figure 1. We searched 11 electronic databases of full-text articles and conference abstracts, i.e., PUBMED (1996–2008), Web of Science (1996–2008), EMBASE (1996–2008), BIOSIS (1996–2008), AIDSLINE (1996–2005), OVID (1996–2008), Psychinfor (1996–2008), Cochrane controlled trials register (1996–2008), DARE (1996–2008), COCHRANE (1996–2008), and ILLUMINA (1996–2007). A total of 5892 references were identified from these 11 databases. After excluding duplicates (the same reference found by two database engines), 3691 citations were considered relevant after the first screen.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada. mark.wainberg@mcgill.ca.

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.

No MeSH data available.


Related in: MedlinePlus