Background: The slow clearance of infected, resting CD4+ T cells in chronically-infected patients poses a major obstacle to viral eradication.  This cellular reservoir of HIV is established even prior to seroconversion.  Its decay has not been previously quantified in patients initiating treatment in primary infection.  We sought to compare the reservoir size and clearance dynamics of patients initiating treatment before or after seroconversion to assess whether early treatment has any effect on viral latency.

Methods: 30 patients initiated HAART within 9 months of seroconversion and achieved plasma viral loads <50 copies/mL. Median follow-up was 12 months; 7 patients were followed for over 3 years.  Patients were stratified by the time of treatment relative to seroconversion.  Total HIV DNA in PBMC was quantified (n=23) by PCR. Quantitative terminal dilution co-cultures were performed (n=19) using PHA-activated CD8-depleted donor cells and anti-CD3/CD4-enriched cells.

Results: Both cell-associated infectivity and viral DNA were initially cleared more rapidly (p=0.04) in patients treated before seroconversion (T_1/2 = 4 months) than in patients treated after seroconversion (T_1/2 = 7 months).  This rapid clearance dissipated by the middle of the second year, after which HIV DNA was eliminated with a median half-life of 18 months. The frequency of CD4+ T cells bearing replication-competent virus after 1 year of HAART was lower in the patients treated before seroconversion.  Both groups had smaller reservoirs (median < 0.2 infectious units per million cells) than has been previously reported during chronic infection.

Conclusions: Patients initiating suppressive antiretroviral therapy before seroconversion initially clear latently-infected cells with a half-life of only 4 months.  Although the clearance of this population falls by the second year on therapy, the net size of the reservoir remains significantly smaller in patients treated earlier.  Thus early treatment may facilitate long-term control or eradication of HIV infection.