Primary HIV infection: molecular approaches in diagnosis and monitoring

The aim of this study was to evaluate, in patients with primary HIV infection (PHI), the modification of HIV molecular parameters (HIV, RNA, and DNA) induced by highly active antiretroviral therapy (HAART) in peripheral blood mononuclear cells (PBMC) and in lymphoid tissue (LNMC).

Nineteen patients with primary HIV infection, 4 women and 15 men with an average age of 35 years (range 27-62), were included in this study. Ten patients received 4 drugs: zidovudine plus lamivudine plus saquinavir plus ritonavir, 7 patients received 3 drugs: zidovudine plus lamivudine plus saquinavir and 2 patients received a different combination of 3 drugs: zidovudine plus lamivudine plus indinavir. As control group we included 8 patients who had been enrolled in a placebo-controlled trial of zidovudine between 1991 and 1995: four received placebo and 4 were treated with zidovudine alone. Peripheral blood samples and lymphoid tissue obtained by echo-driven fine needle biopsies were drawn to monitor molecular HIV parameters. A quantitative in house PCR method in the HIV gag region was used to monitor viral DNA burden and the NASBA system for viremia.

A certain heterogeneity in the baseline values of HIV, DNA, and RNA was observed. Early HAART determined a rapid recovery of the CD4 cell number with normalisation of the CD4/CD8 ratio in most patients. HIV-RNA levels dropped to undetectable levels after a few months of therapy and HIV-DNA was consistently reduced although it never reached undetectable levels. Lymph-node biopsies were well tolerated due to the non-invasive sampling, however an optimisation of the method is needed to improve cell recovery. In the valuable samples the amount of HIV DNA recovered is comparable to that from peripheral blood samples, both at baseline and at follow-up.