Increased HIV infectivity in the acute phase of infection may be a less important factor in HIV transmission than we thought

Assessing, as far as we can, the preventative impact of ART on HIV transmission dynamics is evidently very important – both to inform judgments about ART initiation (Wayal & Hart (STI); Cohen (STI)), and also, at the policy level, to be able to evaluate the possible preventative gains of ART scale-up (Shafer & White (STI); Boily & Mishra (STI)).   One important piece of the jigsaw is the impact of ART on sexual behaviour.  This has been discussed by a number of recent studies (Wayal & Hart (STI); Hogben & Ford (STI); Shafer & White (STI)).  Another piece of the jigsaw is the impact of ART on HIV infectivity.  Of particular concern here are the relatively high levels of infectivity that occur in the period immediately after infection.  In view of this, investigators have stressed the importance of the earliest possible initiation of therapy, if the full preventative benefits of ART are to be enjoyed (Cohen (STI)).

The recent study, Bellan & Meyers (B&M), addresses itself to this second, important but potentially less easily investigable piece of the jigsaw. They observe that investigators have tended to proceed on the basis of the known relationship between viral load and infectivity. Empirical evidence of relative infectivity of acute versus chronic phases of the infection is practically unobtainable, for various reasons.  For a start, newly-infected individuals are rarely diagnosed in the acute phase and, if infected by stable partners may provide no evidence on onward tradition; if susceptible non-infected partners are at risk, then, clearly, ethical guidelines dictate that further transmission be stopped – not investigated.  According to B&M, most subsequent studies have relied for direct epidemiological measurement of acute phase infectivity and duration on a retrospective cohort in Rakai, Uganda (Wawer & Quinn; Hollingsworth & Fraser). B&M reassess previous analyses of this evidence.  They find significant bias – especially in two areas.  The first has to do with the neglect of the contribution to total risk of couples who were censored from the cohort owing to couple dissolution, loss to follow-up or study termination.  The second concerns the extent to which some of the estimated difference in risk between the acute and chronic phases may reflect heterogeneity in the risk behaviour of those couples entering the study sero-discordant, as against those entering it sero-concordant negative.

The findings of B&M are intriguing. They argue that combined effect of these sources of bias in earlier analysis of the Rakai evidence has been enormously to inflate estimates of relative acute phase – relative to chronic phase – HIV infectivity. B&M estimate the relative hazard of transmission during acute phase at 5.3, the acute phase duration at 1.7 months, and the “extra-hazard months” contributed by the acute phase (a measure adopted by the authors in order to ensure comparability of study results) at 8.4. Previous estimates give levels of increased infectivity due to acute phase which are equivalent to between 31 and 141 hazard months. If the results of B&M are confirmed in subsequent studies, the preventative gains of ART scale-up could be greater than hitherto supposed.