Different resistance patterns seen with subtype C HIV in Brazil

Treatment of people infected with HIV B and non-B subtypes in southern Brazil has shown that viral subtype influences likely resistance mutations, according to a new study published in the Journal of Acquired Immune Deficiency Syndromes.

Subtype C is the most prevalent HIV-1 subtype worldwide, dominating the HIV epidemic in India, China and southern Africa. In Brazil, the initial epidemic involved subtype B but the prevalence of subtype C has steadily risen since 1990. In the southern Brazilian state of Rio Grande do Sul, subtype C accounts for 45% of infections. Subtype C is also common in the state of Parana, where it has reached 30% prevalence, and it is increasing in cities such as Rio de Janeiro and Sao Paulo.

Dr Esmeralda Soares and colleagues surveyed HIV subtype and antiretroviral resistance among 77 HIV-infected people attending the Hospital de Clinicas in the southern Brazilian city of Porto Alegre, capital of the Rio Grande Do Sul state.

The hospital treats a large number of people infected with the C subtype, and 40% of the study group were infected with subtype C. The prevalence of other subtypes was: subtype B 45%; subtype F 12%, and mosaic virus (B/F and B/D) 3%.

Just over the half of the study group were women (56%). Average CD4 cell count was 335 cells/mm³ and viral load ranged from undetectable to over one million copies/ml (average 1101 copies/ml). There were no significant differences in average viral load, CD4 count, age, and time since diagnosis by viral subtype. Gender and treatment status were also independent of subtype. However, people with subtype B had been taking anti-HIV treatments for longer than those with subtype C (average 46.6 versus 34.8 months, respectively).

Eighty percent of participants were antiretroviral treatment-experienced: seven had taken non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs), 23 had taken protease inhibitors and NRTIs, and 24 had taken all three drug classes.

Of the 58 treated people, 43% had primary resistance mutations to at least one class of antiretrovirals. Mutations in reverse transcriptase and protease were more common among people with subtype B compared with the C, F and mosaic subtypes. In subtype B, there was an average of 2.24 reverse transcriptase mutations per isolate, whereas subtype C sequences had an average of 0.80 mutations per isolate. Similarly, the average number of mutations in the protease isolate was 0.52 mutations for subtype B and 0.07 for subtype C .

In terms of protease mutations, the mutation at position V82A/F/T/S was more frequent in subtype F compared with subtype B virus (p=0.0209). This mutation occurred in 3 of 21 subtype B patients, 1 of 15 subtype C, 4 of 5 subtype F and 1 of 2 mosaic subtypes. There were no other statistically significant differences in the number of people developing specific protease mutations by subtype. However, it is worth noting that M46I/L occurred in all but the C subtype and L90M only occurred in the B subtype.

The reverse transcriptase mutation M41L was more likely to develop in subtype B than in subtype C, occurring in seven of the B subtypes and none of the non-B subtypes (B vs C p=0.0308; B vs all non-B p=0.011). Four B subtypes developed the nucleoside analogue mutation L210W compared to none of the non-B subtypes, suggesting a trend towards a higher incidence in B subtypes (p= 0.0554).

The authors acknowledge that the greater exposure to antiretroviral therapy in those infected with B subtypes may have influenced their results, and they call for further research comparing B and non-B subtype resistance patterns to confirm these findings.

The authors argue that naturally occurring genetic variations (polymorphisms) associated with non-B subtypes may impact on response to anti-HIV therapy and HIV vaccines, and that this highlights the need for comparative testing of treatments and vaccines in B and non-B subtype populations. Due to the high prevalence of subtype B and C in southern Brazil, Soares and colleagues argue that southern Brazil is an ideal setting for these trials.