| Summary: | The research outlined in this thesis was primarily designed to study the quantitative and qualitative variability of plasma viral RNA during the course of HIV-1 infection. The quantitative aspect involved the development of a highly sensitive and reliable RNA-based PCR method which has been used to detect and quantify HIV RNA load directly from patient materials (plasma, serum). High levels of plasma varaemia were observed during the first stage of HIV-1 infection and considerably higher than those observed in symptomatic patients. However, the high viral loads during this period are transient, and a marked drop in virus quantity was observed with the development of anti-HIV specific immune response. On average, HIV RNA was more abundant in the plasma of patients with more advanced disease compared to asymptomatics. However, the observation of persistent high levels of HIV RNA in some asymptomatic patients suggests that viral replication continues throughout the course of HIV infection and that there is no 'latent' period to correspond with that observed with clinical progression. Extensive studies of sequential variation in the HIV-1 envelope gene constitute the qualitative element of this research and have revealed that there are complex evolutionary patterns. No sequence variation was observed in the V3 and V4 regions in any of the samples collected prior to or immediately after seroconversion, although variation was present in the <i>gag</i> gene at this time. Such an observation led to the suggestion that there is a strong selection for the most rapidly replicating viral variants before the immune response is mounted. However, along with the development of specific anti-HIV immune response, the pattern and process of HIV-1 sequence variation changes. Rapid changes in the viral population were observed within weeks of seroconversion. Phylogenetic analysis of the V3 sequences from patient 82 identified several evolutionary lineages of virus variants after 3 years of infection, only two of which persisted and subsequently reached high frequency.
|
|---|
