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Decay of cell-associated HIV-1 DNA correlates with residual replication in patients treated during acute HIV-1 infection

Yerly, Sabinea; Perneger, Thomas V.b; Vora, Samira; Hirschel, Bernardc; Perrin, Luca

Basic Science

Objectives: To evaluate the decay rate of cell-associated HIV-1 RNA and DNA and to identify factors associated with residual viral load in patients treated at the time of primary HIV-1 infection.

Patients: A group of 15 patients adherent to highly active antiretroviral therapy (HAART) with sustained undetectable HIV-1 viremia for at least 24 months.

Methods: Viremia, cell-associated HIV-1 RNA and DNA in blood and lymph node mononuclear cells were measured using ultrasensitive assays.

Results: Viremia decreased rapidly in all patients; HIV RNA remained < 3 copies/ml in nine patients and fluctuated between 3 and 50 copies/ml in five patients and between 50 and 200 copies/ml in one patient. Decay rates of cell-associated RNA and DNA presented an inflexion point at 1 and 3 months, respectively: first-phase mean half-lives were 0.15 and 0.84 months, respectively, and second-phase mean half-lives were 13.7 and 6.6 months, respectively (95% confidence interval 4.4–13.8). The second phase decay rates were markedly slower, with a DNA decay rate that was highly associated with the mean levels of cell-associated RNA measured in blood from 6 to 33 months (P = 0.001) and in lymph nodes collected at 14 months (P = 0.02).

Conclusions: The clearance of HIV-1 infected cells is correlated with the extent of viral replication as measured by cell-associated RNA levels in both blood and lymph nodes. Quantification of cell-associated RNA and DNA further defines treatment efficacy in ‘aviremic’ patients.

From the aLaboratory of Virology, the bInstitute of Social and Preventive Medicine and Quality of Care Unit and the CAIDS Unit, Division of Infectious Diseases, Geneva University Hospital, Switzerland.

Requests for reprints to Professor L. Perrin, Laboratory of Virology, Geneva University Hospital, 1211 Geneva 14, Switzerland.

Note: Presented in part at the Seventh Conference on Retroviruses and Opprtunistic Infections, San Francisco, 2000.

Received: 8 June 2000;

revised: 22 August 2000; accepted: 4 September 2000.

Sponsorship: This work was supported by the Swiss National AIDS Research Program (grant No 3200.56.059.98) and by a grant from Merck Sharp and Dohme-Chibret, Switzerland.

© 2000 Lippincott Williams & Wilkins, Inc.