Effect of Treatment, during Primary Infection, on Establishment and Clearance of Cellular Reservoirs of HIV-1

• Published in: The Journal of infectious diseases Vol. 191; no. 9; pp. 1410 - 1418
• Main Authors: Strain, Matthew C., Little, Susan J., Daar, Eric S., Havlir, Diane V., Günthard, Huldrych F., Lam, Ruby Y., Daly, Otto A., Nguyen, Juin, Ignacio, Caroline C., Spina, Celsa A., Richman, Douglas D., Wong, Joseph K.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: United States The University of Chicago Press 01-05-2005; University of Chicago Press; Oxford University Press
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - virology; Antiretroviral Therapy, Highly Active; Antiretrovirals; Disease reservoirs; DNA; DNA, Viral - blood; DNA, Viral - genetics; Half lives; Highly active antiretroviral therapy; HIV; HIV 1; HIV Seropositivity; HIV-1 - drug effects; HIV-1 - isolation & purification; HIV/AIDS; Human immunodeficiency virus 1; Humans; Infections; Kinetics; T lymphocytes; Time Factors; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/428777

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3–6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment