In conclusion, the high rates of clustering observed within our study support the assertion that PHI may be associated with an increased risk of onward transmission. The associations we found with younger age, high rates of UAI, and sexual partner change identify this as a high-risk group for HIV transmission. There was a trend towards higher rates of STI in the cluster group on a background of extremely high STI rates in the study population, supporting the argument for increased STI surveillance, particularly of high-risk groups.
The highly significant correlation with CD4 cell counts may represent the early disease stage, or rapid contact tracing and testing of sexual partners of individuals diagnosed with PHI. The plasma viral load at diagnosis was not predictive of clustering, and it is possible that the seminal viral load in men is a more consistent correlate of infectiousness, particularly in the context of genital tract inflammation, with plasma/genital tract discordance playing an important role [7–10]. The presence of the same antiretroviral resistance mutation in one cluster pair, neither of whom had received antiretroviral therapy, illustrates the potential for the secondary spread of such resistant strains, as we have previously documented [33,34]. Our results do not exclude the possibility of a common source for each cluster, rather than transmission within clusters. However, a phylogenetic tree comprising viruses from these 103 primary infections, together with more than 2000 pol sequences from prevalent infections throughout the UK only identified one further potential linkage, and that involved a primary infection case not within an existing cluster (data not shown).
Only 31 of the non-cluster group (64.6%) reported UAI, but it should be noted that this is only in the time window 3 months before diagnosis with PHI. Interestingly, routinely collected data on recent sexual contacts only confirmed three of the linkage pairs that were revealed in the phylogenetic analysis, emphasizing the high rates of anonymous sexual partners and the difficulty in obtaining a reliable sexual history.
Our results provide further evidence that the active management of primary infection will reduce HIV transmission. HIV prevention programmes have been heavily focused on protecting susceptible individuals, but accumulating biological and modelling data suggest that reducing the infectiousness of HIV-positive individuals may also be an effective strategy. A large proportion of PHI remains undiagnosed in the community [35,36], and these findings support the view that as a disease stage PHI represents a major public health threat. Efforts should be re-focused on improving rates of diagnosis of individuals during PHI, timely contact tracing, risk reduction, the management of STI, and possibly early treatment with antiretroviral agents in an effort to break transmission networks during this unique and possibly crucial stage of HIV infection . Furthermore, consideration should be given in information and awareness campaigns to highlight the possible symptoms of PHI in groups with high rates of onward transmission, to encourage such individuals to present to appropriate healthcare providers to enable the timely diagnosis and management of early infection.
M.F. and D. Pillay devised the study. D. Pao, M.F. and G.D. recruited patients for the study. D. Pao, M.F., S.H., C.S. and D. Pillay wrote the manuscript. P.A.C. undertook sequencing and curated the sequences. S.H. undertook the phylogenetic analyses. G.M. undertook the STARHS analysis. C.S. undertook statistical analyses.
The authors would like to thank the Health Protection Agency for funding, and the patients for agreeing to enter this study.
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