HIV becomes integrated into resting CD4 cells much more quickly than previously assumed, presenting new obstacles for post-exposure prophylaxis, primary infection treatment and long-term treatment strategies, according to a report in the November 12 edition of Science.
Following observations of rapid SIV infection of resting CD4 cells in macaques, Dr Ashley Haase and colleagues at the University of Minnesota looked at lymph nodes provided by four individuals with acute HIV infection, and samples from individuals in later stages of HIV infection too.
They found that dissemination of HIV in the acutely infected group mirrored the pattern already seen in macaques, where SIV becomes established in resting CD4 cells at very low levels within days of infection. Once it is integrated into these cells, the virus is not detectable by immune responses and replication cannot be inhibited by most anti-retroviral drugs. This implies that post-exposure prophylaxis must begin within 24 hours of infection, and that treatment during primary infection should ideally include methods of targeting drugs to resting cells.
Previously it was thought that HIV could only replicate in activated cells, and could only infect other activated cells. These findings suggest that during the early stages of infection, the stealthy infection of resting cells allows HIV to evade early immune responses.
Reference
Haase AT et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286: 1353-57, 1999.