Rapid disease progression and the rate of spread of the HIV epidemic

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Traditional HIV epidemic models suggest that rapid disease progression may lead to reduced transmission because of a decreased time for the spread of the virus. We present a transmission model structured by age and duration of infection, and propose that rapid disease progression may lead to higher viraemia at a younger age, when individuals are more sexually active. We suggest that rapid disease progression should be considered as a factor in the scale of the HIV epidemic in Africa.
The rapid spread of heterosexually acquired HIV in Africa compared with the United States has been attributed to a variety of factors. These include higher rates of sexually transmitted diseases and differences in sexual practices [1,2]. However, there is also evidence to support a more rapid rate of disease progression and more rapid increase in viraemia in Africa compared with the USA [3,4]. Traditional epidemic models suggest that rapid disease progression reduces the period for transmission of the virus, and therefore acts to slow the epidemic (intuitively, reduced survival leads to a reduced number of sexual partners and a reduced number of sexual acts during the period of infection) [5]. However, such models do not take into account the effects of age on sexual behaviour. The results of population surveys of sexual behaviour indicate that younger individuals have an increased number of sexual partners and an increased frequency of intercourse compared with older individuals [6]. In addition, recent data indicate that the risk of HIV transmission within stable HIV-discordant partnerships is also higher for young individuals [7]. The reduction in the number of sexual partners with age, coupled with the reduced risk of transmission within a partnership, lead to the conclusion that the older an infected individual, the less likely they are to transmit the virus.
After a brief initial increase in viraemia soon after infection, HIV viral load decreases to lower levels that slowly increase with the duration of infection [8]. More rapid disease progression is associated with progression to a high viraemia earlier and at a younger age. Individuals with a high level of viraemia at a young age will be more sexually active than older individuals and more infectious during the period of high viral load. The effect of age-matching in sexual partnership formation [9,10] results in younger individuals transmitting the virus to predominantly young (and therefore more sexually active) partners. A young primary infective individual is thus not only more likely to transmit the virus, but the secondary infectives of this individual are also more likely to pass it on.
Using a mathematical model of heterosexual HIV transmission structured according to age and duration of infection, it is possible to investigate the effects of increased rates of clinical and virological progression on the long-term size of the HIV epidemic. A comparison of the social, biological and behavioural characteristics of western and African populations reveals their differences, but does not allow analysis of the contribution of disease progression to the rate of HIV epidemic spread. Therefore, the model incorporates data for natural and HIV-associated mortality, changes in HIV viraemia, and sexual activity and sexual mixing derived from studies in western populations. The infected population was structured according to both age and the duration of infection, and the average mortality and viraemia for each group was obtained from empirical data [8,11]. The effects of an increased rate of disease progression were simulated by increasing the rate of progression through the different categories of duration of infection (increasing ‘p ’ in Fig. 1b).

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