Cellular proviral HIV type 1 DNA load persists after long-term RT-inhibitor therapy in HIV type 1 infected persons

Abstract

In a set of 42 antiretroviral naive HIV-1 infected persons who were treated with either Zidovudine (AZT) monotherapy, or a combination of AZT + ddC (Zalcitabine) or AZT + ddI (Didanosine), the HIV-1 DNA load was measured by competitive polymerase chain reaction (PCR) and related to the HIV-1 RNA load in plasma, the CD4+ counts and to clinical markers. The question was whether a reduction in the cellular HIV-1 DNA level contributes to clinical benefit, as predicted by a lasting response in HIV-1 RNA levels in plasma. No significant decline relative to baseline in HIV-1 DNA load was found in the AZT monotherapy arm. In this arm the differences from baseline for both HIV-1 RNA load and CD4+ T cell counts were small and transient. In both combination therapy arms, the maximum mean decline in HIV-1 DNA load was 0.6 log and it never differed significantly from baseline. This is in contrast to plasma HIV-1 RNA load that declined earlier and steeper (mean of 1.5 and 1.9 log for AZT + ddC and AZT + ddI, respectively) and that remained significantly below baseline for 80 weeks. Although 9 of 42 (32%) of the patients under combination therapy had prolonged decreased plasma RNA levels, the proviral HIV-1 DNA remained present in the cells throughout the total follow-up of 144 weeks. In conclusion, combination therapy showed better laboratory parameter responses than AZT monotherapy, in agreement with the clinical data. The HIV-1 DNA sequences did not disappear in any of the patients, heralding renewed active infection after cessation of therapy.