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The present study was aimed at describing the effect of highly active antiretroviral therapy (HAART) in 10 patients with primary HIV infection (PHI). Clearance rates of HIV RNA and HIV DNA in peripheral blood as well as the preexistence and the emergence of drug-resistant strains of HIV were determined over 52 weeks of treatment. The data indicate that HAART is able to induce a suppression of plasma viral load together with a significant decrease, but not a suppression, of peripheral blood mononuclear cell-associated proviral DNA in PHI subjects. Analysis of drug-resistant strains revealed that three PHI patients, showing a complete virologic response, developed mutations in the pol gene, thus suggesting that a persistent residual virus replication exists despite a sustained suppression of plasma viremia.

Twenty years after it was first recognized, the HIVAIDS epidemic continues to expand, but its impact varies greatly in different parts of the World. The worst of the epidemic is now centered in developing countries, especially sub-Saharan Africa, and areas such as Eastern Europe, which was only marginally involved a few years ago but has recently experienced the largest growth in the epidemic. In industrialized countries Highly Active Antiretroviral Therapy (HAART) has changed the natural history of HIVAIDS, causing a reduction in mortality and morbidity due to HIVAIDS and related diseases. Many interlocking factors determine the impact of HAART at the population level, including reduction of morbidity and mortality, changes in the natural history of HIVAIDS and associated illnesses, and the effects of HAART on HIV transmission. To fully appreciate the potential benefits of HAART, the epidemic should continue to be monitored in the future, and the effects of HAART on reducing HIV transmission should also be evaluated. Interventions addressed to encourage the adoption of safer sex practices are badly needed, since a "rebound" in risky sexual behaviors was recently reported among high risk groups, which is, at least in part, attributable to the optimism about new treatments.

Our objective was to describe morphologic and metabolic disorders in patients treated with highly active antiretroviral therapy (HAART) since primary HIV infection (PHI). Our method was prospective evaluation of patients with PHI initiating HAART at the time of diagnosis. Outcome measures were: development of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and of body shape abnormalities indicative of lipodystrophy, assessed through self-reported questionnaires and physical examination. Results:From May 1997 to April 2001, 41 patients (35 males) with PHI presented at the National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy. A protease inhibitor-including regimen was started in 30 patients, and a nonnucleoside reverse transcriptase-inhibitor in 11. Median interval between enrollment and treatment initiation was 30 days (mean 39, range 10-150). Median HAART duration was 19 months (mean 21.2, range 3-47). Thirty-eight patients had undetectable (less than 80 cpmL) HIV RNA after a median of 3 months (mean 4.1, range 1-15). Mean CD4 cells count increased from 632mmc at baseline to 936mmc at the last follow up. No cases of hyperglycemia (glucose level greater than 110 mgdL) were observed. After a median of 6 months on HAART, 10 patients developed beyond grade 2 (greater than 240 mgdL) hypercholesterolemia, 5 developed beyond grade 2 (greater than 400 mgdL) hypertrygliceridemia, and two developed both. Body mass index did not change significantly. Five patients (12.2) developed lipodystrophy after a median of 14.5 months (mean 15.3, range 2-30), with an incidence of 7.3 per 100 patient-years. Conclusions:Dyslipidemia and lipodystrophy can occur in patients treated with HAART since PHI. This risk of should be taken into account when considering this early antiretroviral treatment of HIV infection.

During HIV disease an increased in vitroapoptosis of peripheral blood mononuclear cells has been demonstrated. This can be reversed in vitroby interleukin (IL)-2. Recent trials with highly active antiretroviral therapy (HAART) and IL-2 in HIV-1-infected patients showed promising immunological and clinical results. Here we investigated the effects of subcutaneous low-dose IL-2 administration in combination with HAART on in vitroapoptosis and the relationship between apoptosis, CD4+counts, and HIV replication. Twenty-two asymptomatic HIV patients were randomized for HAART (arm I) and HAART plus IL-2 (arm II). Spontaneous apoptosis was decreased in both arms after 28 weeks of therapy but the reduction was highly significant only in arm II (P= 0.05 vs P= 0.001). As the percentage of apoptosis decreased, there was a significantly higher increase of both CD4+and CD4+naive T cells in arm II vs arm I. HIV plasma viremia was reduced in all patients after therapy. Our data suggest that intermittent therapy with low-dose subcutaneous IL-2 in addition to HAART induces a positive immunomodulation in asymptomatic HIV-infected patients.