Background:  Transmission is enhanced during primary HIV infection. The extent to which HIV epidemics are driven by transmission during primary infection is a vital determinant of the efficacy of ART as a means of preventing onwards transmission, and also on the potential for drug resistant mutants to spread. We propose that epidemiologically, the role of primary infection has been overstated, and consequently that the potential for antiretroviral therapy to halt the generalised spread of HIV may be greater than previously thought. Recently, several studies have elucidated the dependence of transmission on both viral load and stage of disease progression.

Methods:  We review these, and reanalyze the data based on a new mathematical model, and test our model against a variety of observations.

Results:  We estimate that relative to the asymptomatic stage, infectiousness is enhanced 26-fold in primary infection and 3.6-fold during pre-AIDS/AIDS. The enhancement of infectiousness during primary infection cannot be explained solely in terms of higher viral loads: the virus is estimated to be 8-fold more infectious at this stage. However, to estimate the total transmission potential of each stage, account must be taken of their relative duration, and we estimate that for a typical index case followed over the whole course of untreated infection, only 14% of onward transmission occurs in primary infection while 46% occurs in the asymptomatic stage and 40% occurs in pre-AIDS/AIDS. From this perspective, primary infection plays only a minor role in transmission because of its very short duration relative to the other stages. We show that the net proportion of infections attributable to primary infection is substantially greater in early epidemics and in high risk groups.

Conclusions:  Within the context of a generalized epidemic, ART may have a large effect in reducing onward transmission even if given after primary infection, but before pre-AIDS/AIDS. The transmission of drug resistant strains during the infectious pre-AIDS/AIDS stage may however be a major problem which would only become apparent very gradually, but key parameters relating to transmission fitness of resistant strains upon which this depends have not yet been adequately measured.