Virus burden in lymph nodes and blood of subjects with primary human immunodeficiency virus type 1 infection on bitherapy

At present, it is not known whether undetectable plasma viremia corresponds to an absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid tissues. This issue has been explored in 11 subjects with primary HIV-1 infection treated with zidovudine plus didanosine by evaluating virologic markers in blood and lymphoid tissues 9-18 months after initiation of treatment. These markers include plasma viremia, measured with a sensitive assay with a detection limit of 20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node mononuclear cells, and HIV-1 RNA in lymphoid tissue. Five subjects had plasma viremia <20 copies/mL and showed no evidence of viral replication in lymphoid tissue. Six subjects had both detectable plasma viremia and evidence of HIV-1 RNA in lymphoid tissue. The results indicate that absence of detectable HIV RNA in lymphoid tissue is associated with viremia levels of HIV-1 RNA <20 copies/mL

Zidovudine plus didanosine in primary HIV-1 infection

Viraemia levels in the months following primary HIV-1 infection (PHI) predict the subsequent course of the infection. Inhibition of viral replication in PHI patients might improve their clinical prognosis. In this study, we evaluated the antiviral efficacy of the association of two reverse transcriptase inhibitors--zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12 patients treated for at least 6 months (median 10 months, range 6-15 months). We compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients with two historical control groups consisting of 16 untreated patients and 15 patients on zidovudine therapy. Significantly lower viraemia was observed between 3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine-didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12 months. Only one of the 31 historical control patients had undetectable viraemia. For proviral DNA, smaller differences between groups were observed, although with time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four patients from the zidovudine-didanosine group versus one in the control groups. Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine group and none of the patients in this group developed HIV-1-associated clinical complications. These data suggest a higher efficacy of combined therapy compared with zidovudine monotherapy in PHI patients and indicate that control of viraemia for at least 1 year is achievable in PHI patients