January 31, 2000
Slide 211 looked at the immunologic impact of several HAART regimens, which were started in infants less than three months of age. 17 children were studied using four different regimens. Regimens included ZDV/ddI/NVP; ZDV/3TC/NVP; ZDV/3TC/NVP/ABC; and d4T/3TC/NVP/NFV. Mean baseline viral load was >100,000/ml. All infants were able to achieve undetectable (<50 copies/ml) within the first year. CD4 counts normalized to normal levels appropriate for age. Immune function tests were also performed. Lymphocyte proliferation assays (LPA) and cytoxic T-cell (CTL) assays could not detect any HIV specific immune responses after one year. These data demonstrate that HAART therapy is highly effective in reducing viral load and infectious virus in babies. The authors concluded that given the normalization of T-cell numbers and lack of HIV specific immune responses, early HAART treatment might impact HIV's ability to establish infection.
Slide 212 looked at the question of whether patients with primary HIV infection are epidemiologically linked. 36 patients from several locations in the US were studied. Several of these patients were previously found to have mutations and evidence of phenotypic resistance to protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Each patient's viral strain was analyzed by population based sequencing and phenotypic resistance testing. There did not appear to be any geographic clustering of viral strains when the sequences were analyzed for their degree of relatedness. Three patient pairs were found that had a high degree of relatedness when their sequences were analyzed. One pair of patients was separated by over two years of time between infections. In two pairs, both patients exhibited evidence of NNRTI resistance, while in the third pair only one of two did. The authors concluded that the observation of NNRTI resistance in newly infected and previously untreated patients is not related to transmission of a particular strain of resistant virus. Rather these low-level resistant viruses are probably naturally occurring, related to the ongoing replication and evolution of virus in untreated patients.