Treating HIV primary infection may have only a limited impact on reducing the spread of HIV because most people are infected by people with chronic HIV infection, according to a Dutch study presented at the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris on July 14th.
Although the effect of treatment during primary infection on the later course of HIV disease has yet to be established, epidemiologists have often suggested that as people newly infected with HIV have very high viral loads, and are consequently very infectious, treatment during primary infection might present an opportunity to slow the spread of HIV.
This theory was tested by investigators in the Netherlands who developed a mathematical model of HIV spread amongst gay men in Amsterdam who were unaware of their HIV status.
In the model men with primary HIV infection were considered 20 times more infectious than men with chronic HIV infection. Primary infection was considered to be the first three months after infection with HIV.
The Dutch investigators also designed their model to assess the extent to which HIV was being spread in two relationship categories: steady relationships lasting an average of 18 months, and casual sexual encounters. These categories were not mutually exclusive.
Sexual behaviour patterns were obtained from the ongoing Amsterdam Cohort Study of HIV risk behaviour and prevalence amongst young gay men'. On the basis of data from this cohort, investigators included in their model had an average of 30 acts of unprotected anal sex between steady partners a year, and two acts of unprotected sex a year for men reporting only casual sexual encounters.
HIV incidence amongst gay men in the Amsterdam cohort is 1% a year. The investigators’ model suggested that treatment during primary infection would make little impact on the growth of the HIV epidemic amongst Amsterdam's gay men as 89% of new infections were the result of onward HIV transmission from men with chronic HIV infection.
In addition, a clear majority of new infections would occur as a result of unprotected sex during casual sex, with 43% of new infections occurring in the context of steady relationships.
However, the investigators also modelled for a sexual environment where men were engaged in higher rates of partner exchange, and were having more unprotected anal sex resulting in an annual HIV incidence rate of 5%. In this model, the number of new HIV infections occurring during primary infection increased to 28%, with 86% of new infections happening as a consequence of casual sexual encounters.
The investigators therefore concluded that most new HIV infections in Amsterdam were currently due to men with chronic HIV infection, and that treating primary infection would have only a limited impact on the spread of HIV in the city. However, should the sexual behaviour patterns of gay men change, then substantially more new infections would be due to men with primary infection and early treatment could have a major impact on this.
It will be important to replicate this type of study in a high prevelance heterosexual population in order to determine the potential impact of introducing antiretroviral therapy on transmission. Data from Uganda have shown that HIV transmission is strongly associated with high viral load (>100,000 copies/ml), whilst other data show a greater risk of transmission from individuals with CD4 cell counts below 200 cells/mm3.
However, as programmes scale up treatment, they will treat those who are symptomatic first of all. This group may not contribute a large proportion of new infections to ongoing incidence, given their poor state of health. Also, if treatment programmes are unable to accomodate all who are in the highest risk group for transmission, the impact of treatment on onward transmission may appear disappointing. Models will need to take these factors into account.
Xiridou M et al. HIV transmission during primary versus secondary HIV infection. Antiviral Therapy 8 (suppl. 1), abstract 82, 206, 2003.