Are African HIV epidemics sustained by exogenous introduction of infection?

What is the relative importance of exogenous and endogenous transmission in sustaining HIV epidemics?  In a study of HIV sub-type distribution in the Middle East, Mumtaz & Abu Raddad (STIs) stress the role of multiple exogenous introductions, as evidenced in the wide diversity of genetic sub-types present in most countries.  At a more local level, the answer to our question will, of course, depend on how “exogenous” and “endogenous” are defined – and may have little meaning where we are concerned with the  HIV transmission networks in gay communities that are the object of a number of studies featured in STIs (Potterat & Muth (STIs); Drumright & Frost (STIs)).  Yet, the situation is surely very different when it comes to the kind of geographical communities that are constituted by the studies designed to evaluate the local epidemiological effect of ART deployment – such as HPTN 071 study in Zambian and South Africa.  Here, the location of the communities targeted by the trial establishes a clear boundary, and gives meaning and importance to our question.  How far are the preventative effects of ART coverage within the community likely to be neutralized by introductions that are exogenous to it?

Grabowski & Ray, in recent analysis of data deriving from the Rakai Community Cohort Study, Round 13 (2008-9), has sought to give some insight into the spatial dynamics of HIV transmission, through investigating a cohort of 14,594 individuals in 46/50 communities in the Rakai region of Uganda.  Its goal: to determine the relative epidemiological importance, in this particular context, of transmissions within the household, across the boundary of the household but within the community, and across boundary of the community.  A difficulty foreseen by the study is that transmissions from outside tend to be less easily traced.  The researchers have therefore adopted a multi-faceted approach:  an analysis of the spatial clustering (1) and a phylogenetic analysis (2) are complemented by an analysis of individual partnerships on the basis of data supplied at interview (3).  The phylogenetic analysis investigated the relationship of phylogenetic clustering (in terms of genetic closeness in the gag and env genes) to geographical location.

The findings of the study suggest the relative importance of repeated introductions of HIV across the community, and indeed, regional boundary, as against the importance of onward transmission through intra-community networks (other than those within the household).  The spatial clustering analysis shows very strong household clustering (RR of HIV+ person, as opposed to non-HIV+ person, being in the same household as another HIV+ person 3.2, and RR 10.8 for incident cases), but practically no clustering outside the household.  The phylogenetic analysis identified 95 clusters, of which 53 (55.8%) spanned households; of these 53, 38 (71.7%) crossed community boundaries; of the 38, 18 (47.4%) spanned geographic regions.  The individual transmission analysis shows 39.5% of new cases from extra-household partners; of these, 62.1% were from partners outside the community; of these (where location of partner was known) 50% outside Rakai district, and geographically dispersed throughout Uganda.

Taken together, the three analyses seem to offer a consistent picture. The surprise is the importance of more exogenous, as against more endogenous, transmissions, with intra-community transmission (excepting within the household) not playing the role that might have been expected.  Of course, these findings may not be generalizable to other sub-Saharan, still less non-African, settings.  But they do raise pertinent questions  to any attempts to evaluate the preventative possibilities of localized ART interventions.