Cellular proviral HIV type 1 DNA load persists after long-term RT-inhibitor therapy in HIV type 1 infected persons.
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.
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Clinical Viro-Immunology, Amsterdam.
S M
SM
Bruisten
P
P
Reiss
A E
AE
Loeliger
P
P
van Swieten
R
R
Schuurman
C A
CA
Boucher
G J
GJ
Weverling
J G
JG
Huisman
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis*; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load; D016047:Zalcitabine / Q000008:administration & dosage / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017931:DNA Primers; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine