Abstract
Several AIDS cohort studies observe that the incubation period between HIV infection and AIDS onset can be shorter than 3 years in about 10% seropositive individuals, or longer than 10 years in about 10-15% individuals. On the other hand, many individuals remain seronegative even after multiple exposures to HIV. These distinct outcomes have recently been correlated with some mutant genes in HIV co-receptors (e.g., CCR5,CCR2 and CXCR4). For instance, the mutant alleles △32 and m303 of CCR5 may provide full protection against HIV infection in homozygotes and partial protection in heterozygotes; moreover, infected heterozygotes may progress more slowly than individuals who have no mutant alleles. Frequencies of these mutant alleles are not very low in Caucasian populations, therefore, their effects may not be insignificant. Based on available data, we propose a one-sex model with susceptibles classified as having no, partial or full natural resistance to HIV infection, and infecteds classified as rapid, normal or slow progressors. Our goals are to investigate the impact of such heterogeneity on the spread of HIV and to identify key parameters. The basic reproductive numberR0is derived from a simplified model. The relative contributions toR0from the three groups of infecteds are investigated. We present a rough estimating procedure making use of limited data to estimate some new parameters specific to our model. Finally the rough estimating procedure is applied to an example focusing on CCR5-△32 in San Francisco gay men. The relative contributions toR0among the three infected groups are compared using two different classifying criteria for infecteds. Under given assumptions, we conclude that, without any intervention, HIV infection will continue to spread in this population and the epidemic is mainly driven by the normal progressors. The transmission rates from infecteds are identified as key parameters.
Highlights
The studies of Sheppard, Lang and Ascher (1993) and Phair (1994) find that about 10- 15% of HIV infected individuals remain AIDS free for 10 years or longer, while another 10%progress within the first 2-3 years
As the first step in our efforts to incorporate genetic heterogeneity in epidemiological models, we focus on the simplest possible scenario, i.e., a homosexually-active homogeneously-mixing population, to investigate the role of differential susceptibility and pathogenesis in HIV infected populations
Most individuals do not know their genotypes at loci related to HIV susceptibility orland AIDS pathogenesis, it is reasonable to assume that genetic heterogeneity does not influence pairing behavior
Summary
The studies of Sheppard, Lang and Ascher (1993) and Phair (1994) find that about 10- 15% of HIV infected individuals remain AIDS free for 10 years or longer (non-progressors), while another 10%progress within the first 2-3 years (rapid progressors). In a cohort of HIV-1 infected Caucasian patients, the heterozygote frequency is 35% lower than in the general population and no homozygotes with two A32 alleles are found These observations suggest A32 may provide, at least partial, resistance to HIV-1 infection. (1997) describe a mutation, 641, which occurs at an allele frequency of 10- 15% among Caucasians and African Americans This mutant gene dose not seem to provide protection against HIV-1 infection, it does indicate a 2-4 years delay of progression among infecteds. All the information above clearly indicates the existence of genetic heterogeneity with respect to susceptibility to HIV infection and to rate of AIDS progression in general populations. Such kind of heterogeneity has not been studied in the modeling literature.
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