This study evaluates the prevalence of HIV-1 subtypes and PR and RT drug resistance mutations among HIV-1-infected immigrants living in Southern Spain. Immigration had been gradually increasing since 2000, with a peak of 22% in 2008. Since then, it has been slowly decreasing to 11.8% in 2010. The largest immigrant group was form Central-South America (47.9%) most of them infected with the HIV-1 B subtype. However, up to 25% of immigrants were from countries where HIV-1 non-B subtypes are predominant, as Sub-Saharan Africa with 79% of HIV-1 non-B subtypes (subtypes A, G, J or CRF02_AG), or Eastern Europe with 60% (subtypes A, F, CRF02_AG or CRF01_AE). This marked increase in individuals infected with non-B HIV-1 subtype in our society may have a direct impact on the spread of these subtypes among Spanish native individuals in addition to the changes in appropriate treatment regimes due to differences in genetic sequences amongst the different HIV-1 strains. These results are similar to those found in studies conducted in other regions in Spain, Madrid and Canary Islands [19, 20, 22].
Previous studies reported a high prevalence of minor resistance mutations in naïve patients infected with HIV-1 non-B subtype that could facilitate the emergence of major mutations [16, 23, 24]. However, the clinical relevance of minor mutations is unclear. Our results indicated that patients infected with HIV-1 non-B subtypes showed a high frequency of minor PR mutations (polymorphisms) as M36I, L63P, and K20R/I, in contrast to the low proportion of major resistance mutations. In fact, only one patient, subtype CRF02_AG, had L90M mutation probably as a result of receiving antiretroviral therapy during two years (1/28, 3.5%). No difference between the number of patients with major or minor RT mutations (3/28, 10.7% in both cases) was found. Nevertheless, the proportion of patients with major RT mutations was higher compared to patients with major PR mutations.
It is of note that one treatment naïve patient, with G subtype, showed major RT mutations associated with resistance to NRTI (K70R) and NNRTI (A98G). This patient might have acquired these resistance mutations at the moment of infection. One limitation of our study was the impossibility to test plasma samples of antiretroviral-experienced patients before the initiation of antiretroviral therapy to determine primary resistance mutations.
An increasing effort has been done to characterize the difference in antiretroviral therapy responses within HIV-1 non-B subtypes. Although clinical evidence remains limited, response to antiretroviral therapy does not appear to differ significantly among subtypes . In our study, 29 patients showed HIV-1 non-B subtype in PR and/or RT. Eleven of them were under antiretroviral therapy and had good virological and immunological responses. Nevertheless, larger cohorts are necessary to confirm our results. On the other hand, 14 immigrants infected by HIV-1 non-B subtype were naïve for antiretroviral therapy. Most of them with viral load around 4 log HIV-1 copies/ml, and two patients had undetectable viral load for a long period of time (one of them at least for one year). As previous studies have described the failure of laboratory techniques to detect HIV-1 non-B subtypes [25–27], however it would be interesting to establish whether the failure of the diagnosis may be due to a phenotype characteristic of viral load controller in this population.