RATES OF HIV DISEASE PROGRESSION
Marked individual variation in the rate of HIV disease progression occurs, and to date, a number of individuals with minimal or no disease progression over prolonged periods have been described.6-7 Multiple definitions were used in the studies cited below, but in general, the term long-term nonprogressors (LTNPs) was applied to individuals who maintain a stable CD4 T lymphocyte count >500∕mm3 for prolonged periods after infection (>10 years in most series) in the absence of antiretroviral therapy.6 These individuals remain asymptomatic, and the majority have low HIV-1 viral loads.8-10 In many cases, these individuals have stronger HIV-specific CD8 T lymphocyte responses and higher titers of neutralizing antibodies against HIV-1 than do individuals with progressive HIV disease.
More vigorous HIV-specific CD4 T lymphocyte responses are a feature of individuals who control HIV replication without antiretroviral therapy11 and may be a feature associated with LTNPs.11,12 Lymph-node architecture is less affected than in those with progressive disease. Many LTNPs do, however, demonstrate lower CD4 T lymphocyte counts than HIV- seronegative controls,6 and CD4 T lymphocyte counts may decline over longer periods of followup in association with a gradual failure in HIV-specific CD8 T lymphocyte responses.13 Thus, some LTNPs will develop progressive disease on more extended follow-up, even in the presence of attenuated virus, and are more accurately long-term survivors (LTSs) or slow progressors (SPs), not LTNPs.14 It, therefore, becomes apparent that so-called LTNPs are a heterogeneous group that represents part of a continuum of disease progression with individuals with progressive disease.15 At the other extreme, individuals who progressed to acquired immunodeficiency syndrome (AIDS) over relatively short periods (to demonstrate a distinct phenotype in comparison to individuals homozygous for the CCR5 wild-type allele.40