Other subtypes

There is also evidence of resistance-related polymorphisms in other HIV subtypes. For example, two reverse transcriptase mutations (A98S and R211S) and two protease inhibitor-related mutations (M46L and 19P) have been identified in subtype G virus among a Spanish cohort.

In a study comparing resistance mutations that developed during treatment with nelfinavir, I54V/L, a mutation not selected in subtype B was seen in subtype G isolates. The L90M mutation had a greater effect on subtype B than it it did on subtype G and while L90M reduced susceptibility to saquinavir in subtype B, it did not do the same in subtype G. I54V/L-L90M reduced the susceptibility of subtype B to indinavir and saquinavir and again, this did not happen in subtype G.

Additionally, the M46I/L, I84V, and V82A/F/T mutations associated with indinavir developed earlier in subtype B than in subtype G isolates. The mutation M89I was seen in subtype G infection and not in subtype B.1

In subtype B, 66% of virus showed the D30N mutation (strongly associated with N88D), 28% had the L90M and 6% had N88S. In contrast, 74% of subtype G virus showed the L90M mutation, 12% D30N, 10% N88S, 5% I54V/L and 2% L46I.2

There is also evidence of a difference in the 82 mutation in subtypes B and G seen during tipranavir therapy. Mutation 82A was more common in subtype B but 82T and 82S predominate in subtype G.2

Analysis of subtype CRF02_AG in Ghana found no key PI resistance mutation but phenotypic testing showed that the virus was much less susceptible to nelfinavir and lopinavir and moderately less susceptible to indinavir and saquinavir than B subtypes.3 In patients failing nelfinavir therapy, the D30N mutation was seen in subtype B and not in CRF02_AG, in which the 88S mutation emerged.4

HIV subtype D in infants exposed to nevirapine displayed a high level of resistance. Interestingly, the resistance profile was I135L, T139V and V245T. This is quite distinct from the usual NNRTI resistance mutations of Y181C, K103N and G190A.5

In NRTI-resistant isolates from subtype F samples in Brazil, mutations occurred more commonly at position 211 rather than 210.6 

Quite a number of studies have documented the importance of the V106M mutation in non-B subtype resistance to efavirenz and nevirapine.7 

References

  1. Santos AF et al. Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. J Antimicrob Chemother 63(3): 593-599., 2009
  2. Camacho R et al. Different substitutions under drug pressure at protease codon 82 in HIV-1 subtype G compared to subtype B infected individuals including a novel I82M resistance mutation. Antivir Ther 10: S151, 2005
  3. Kinmoto M et al. HIV-1 proteases from drug-naive West African patients are differentially less susceptible to protease inhibitors. Clin Infect Dis 41: 243-251, 2005
  4. Ariyoshi K et al. Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection. J Acquir Immune Defic Syndr 33:336-342., 2003
  5. Baird H et al. Novel mechanisms involved in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance of both the subtype D HIV-1 isolate and reverse transcriptase derived from a drug-naïve Ugandan. Antivir Ther 9: S35, 2004
  6. Calvacanti AM et al. Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil. Mem Inst Oswaldo Cruz 102:785-792, 2007
  7. Martinez-Cajas J et al. Differences in resistance mutations among HIV-1 non-subtype B infections: a systematic review of evidence (1996-2008). J Int AIDS Soc 12(1): 11, 2009
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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