Prevalence of X4 tropic viruses in patients recently infected with HIV-1 and lack of association with transmission of drug resistance

Abstract

HIV-1 co-receptor usage may play a critical role in AIDS pathogenesis. Information on viral tropism in HIV-1 seroconverters is scarce, as is the relationship with transmission of drug-resistant viruses. All consecutive HIV-1 seroconverters seen between January 1997 and December 2005 in 17 Spanish hospitals were retrospectively analysed. V3 loop amino acid sequences derived from plasma RNA at the time of initial diagnosis were used to predict co-receptor usage. Major drug resistance mutations, plasma HIV RNA, CD4 counts and HIV subtype were considered for subsequent analyses. A total of 296 HIV-1 seroconverters were identified (84% male; median age 30 years; 61% homosexual men). Median estimated time from infection was 7 months (interquartile range, 3-11). Primary drug resistance mutations were seen in 12.5%, being 9.5% for nucleoside reverse transcriptase inhibitors (NRTI), 4.4% for non-NRTI (NNRTI) and 3% for protease inhibitors (PI). Twenty-four (8.1%) carried non-B subtypes. HIV tropism could be characterized in 203 seroconverters (69%). X4 viruses (either pure or dual/mixed R5/X4) were recognized in 35 (17.2%). There was no association between HIV tropism and mean plasma HIV RNA (4.5 versus 4.4 log copies/mL in R5 versus X4, respectively; P = 0.45) or mean CD4 counts (594 versus 554 cells/mm(3), respectively; P = 0.48). The proportion of X4 viruses did not differ in patients infected with wild-type or drug-resistant viruses (17% versus 18%, P = 1). Intravenous drug users tended to show X4 viruses more frequently than individuals infected by sexual relationships (35.7% versus 16.5%, respectively; P = 0.073). After 12 months of follow-up in 78 seroconverters who did not start antiretroviral therapy, more pronounced increases in plasma HIV RNA (+5056 versus -3430) and declines in CD4 cell counts (-126 versus -60) were seen in X4 compared with R5 carriers. A significant proportion of recent HIV-1 seroconverters harbour X4 viruses (17.2%), without any evidence of association between co-receptor usage, transmission of drug-resistant viruses and HIV subtype.