Failing treatment boosts transmission risk from urethritis

People with HIV who acquire a sexually transmitted infection whilst their viral load is above the limit of detection are much more likely to transmit HIV infection, according to the findings of a UK study published today in the journal AIDS.

“This is obviously of concern, particularly with the new impetus to provide affordable antiretrovirals in the developing world, where the overlap between HIV infection and sexually transmitted infections is so large” said Dr Tariq Sadiq, Clinical Reseach Fellow in the Department of Sexually Transmitted Diseases, London.

Twenty four men newly diagnosed with urethritis who had been taking antiretrovirals for at least three months were recruited at Mortimer Market Clinic in London and by Dr Steven Taylor at Heartlands Hospital in Birmingham. Sixteen men on antiretroviral therapy without urethritis were also recruited as a control group.

Eighteen men with urethritis had plasma viral load below 50 copies/ml before being diagnosed with urethritis, and only two had detectable viral load in semen after a urethritis diagnosis, with no apparent difference between chlamydial, gonococcal or non-gonococcal urethritis. In cases where virus was detectable in semen, the viral load did not rise above 6,000 copies/ml.

In seven men with detectable plasma viral load before urethritis was diagnosed, virus levels in semen were much higher. Four men had detectable virus in semen, and it remained detectable at the third clinic visit, despite treatment for urethritis. In one case, a patient with a plasma viral load of 5,300 copies/ml prior to diagnosis of urethritis was found to have seminal viral load of 100,000 copies/ml. Following treatment for urethritis, seminal viral load fell below 5,000 copies despite a 1 log increase in plasma viremia. In the three remaining cases, there was little change in seminal viral load after treatment, suggesting that seminal viremia may have been influenced by other factors. In each case, plasma viremia also remained detectable throughout the study period.

The authors speculate that anti-HIV treatment may still have been sufficiently effective to limit the effects of urethritis on virus production, or that the effect of urethritis might be too small to be detectable in patients with high seminal viremia. In the absence of semen samples that pre-date the diagnosis of urethritis, this question remains unanswerable.

Amongst the control group, seminal HIV RNA was detectable in three patients, one of whom had viral load below 50 copies at baseline and then subsequently experienced a viral load increase above 1,000 copies. Another patient with slowly rising plasma viral load (from 200 to 1300 copies during the study) also maintained detectable seminal viremia during throughout the study.

A larger study to examine the effects of urethritis on seminal viremia in people on HAART is now being organized in the UK. Called the ESCAPE study, it is recruiting patients at the Mortimer Market Centre in London and Heartlands Hospital in Birmingham, and will start recruiting patients at Brighton’s Royal Sussex County Hospital in April.