HIV subtype A6 with the L74I polymorphism, which increases the risk of cabotegravir/rilpivirine treatment failure, causes more and more infections in Poland. In this multicenter, observational, cross-sectional study (2023–2024), we analyzed viral subtypes and drug-resistance mutations to drugs used for long-acting injectable antiretroviral treatment and pre-exposure prophylaxis. Among 357 people with HIV, 247 (69%) were Polish nationals, and 102 (29%) were from former Soviet Union countries. Of the 357 people included, 159 (45%) had subtype B, and 177 (50%) had subtype A6 infections, with 165 (87%) of the latter characterized by the L74I polymorphism. Subtype A6 was more frequent in women (66% vs. 46% in men, p < 0.05) and among people from former Soviet countries (77% vs. 39% in Polish nationals, p < 0.05). About 40% of people had either drug-resistance mutations for cabotegravir/rilpivirine or HIV A6 subtype with the L74I polymorphism; 4.5% had both of these conditions. Compared to subtype B infections, subtype A6 infections were characterized by more frequent major transmitted drug-resistance mutations for non-nucleoside reverse transcriptase inhibitors (8.5% vs. 1.9%, p = 0.007) and rilpivirine (5.1% vs. 0.6%, p = 0.016). Due to the frequent occurrence of the L74I polymorphism and drug-resistance mutations in HIV A6 subtype infection, about 40% of people with HIV in Poland may be at risk of long-acting injectable treatment failure.

Some people with Human Immunodeficiency Virus (HIV) on effective antiretroviral therapy have persistent low lymphocyte CD4 counts and remain at an increased risk of Acquired Immunodeficiency Syndrome (AIDS). We investigated whether primary drug resistance mutations (DRMs) and HIV-1 subtype could be related to immunologic reconstitution in these people. In a multicenter, observational cohort study among treatment-naïve patients, we analyzed HIV-1 subtype, primary drug resistance mutations, CD4 counts, and CD4:CD8 ratios during effective antiretroviral therapy. We compared these variables between patients with different HIV subtypes and between those with or without drug-resistance mutations up to 48 weeks post-baseline. In 156 patients, CD4 count normalization (≥500 cells/µL) was observed in 39% of patients, while CD4:CD8 ratio ≥ 1 in 27% after treatment implementation. HIV-1 subtype B was present in 75% of the patients and subtype A in 22%. Primary resistance mutations were found in 57% of the individuals. The percentage of immunological nonrespondents did not differ significantly between those with different HIV subtypes or between those with or without primary resistance mutations (p > 0.05). In conclusion, there was no significant coincidence between the HIV subtype and primary drug resistance mutations with immunological reconstitution in patients receiving effective antiretroviral therapy.