Sadiq, Syed Tariq; (2005) The effects of sexually transmitted infections on the biological correlates of HIV-1 transmissions and pathogenesis in homosexual men. Doctoral thesis , UCL (University College London).

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Abstract

In men, the concentration of HIV-1 RNA in semen is an important determinant of HIV-1 infectivity. In sub-Saharan Africa, urethritis has been associated with increases in seminal plasma HIV-1 RNA load in those not receiving antiretroviral therapy. Less is known of the impact of urethritis both within the developed world and in those receiving antiretroviral therapy. In-vitro evidence also suggests that syphilis may stimulate HIV-1 replication, potentially impacting on HIV-1 disease progression as well as its transmission. In this thesis I present a series of studies that examine the effects of urethritis (due to gonorrhoea, chlamydia or NSU), early syphilis and their treatments on HIV-1 RNA loads in blood and semen in homosexual men in the UK. The impact of urethritis on the presence of drug-resistant HIV-1 mutants found in semen among those receiving antiretroviral therapy was also analysed. In addition, effects on CD4 counts were examined in those with early syphilis. Finally a study on the feasibility of research involving semen donation is presented. The research demonstrates that gonococcal and chlamydial urethritis, but not NSU, increase HFV-l RNA load in semen. In comparison with the increases previously demonstrated in Africa, the relative effects were similar but the absolute increases were smaller. Minimal effect was seen in those on suppressive antiretroviral therapy but among those on poorly suppressive antiretroviral regimes and those with gonococcal infection HIV-1 RNA loads in semen were high. In these patients multi-drug resistant HIV-1 was found in both genital and systemic compartments. The studies also demonstrate very little effect of early syphilis on either blood or semen plasma viral loads. However, early syphilis, particularly early latent syphilis, was associated with a reduction in CD4 count that was reversible on syphilis treatment. Studies involving semen donation in symptomatic homosexual men were shown to be feasible.

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