Poor adherence was the single factor most likely to result in HIV being detectable in the semen of men taking anti-HIV drugs in a Brazilian study published in the April 2003 edition of the Journal of Acquired Immune Deficiency Syndromes.
The study involved 93 men, 70% of whom were gay, who were naive to anti-HIV therapy and started taking either a dual nucleoside combination (86%) or triple combination of drugs including a protease inhibitor (14%) between 1996 and 1998. Dual nucleoside therapy was, at this time, the standard of care in Brazil.
Patients visited the clinic in Rio de Janerio for follow-up visits one month after starting therapy, and then at month two, month three and month six. At each visit a physical examination was conducted and detailed questions were asked about sexual health and adherence to anti-HIV therapy. Patients who reported to taking their drugs everyday, at least 80% of the time were categorised as adherent - a measure of adherence which would be widely regarded as suboptimal. Sexual health checks were conducted, and patients with either an ulcerative infection or an infection causing discharge from the penis were excluded from the study. Other patients were asked to provide a semen sample after 48 hours with no other ejaculation.
At baseline average HIV plasma viral load was 47,000 copies/ml, with four patients having a viral load below the limit of detection (400 copies/ml). Median CD4 cell count was 269 cells/mm3. Average HIV viral load in semen was 7,800 copies/ml, with 24% of patients having an undetectable seminal viral load.
On univariate analysis, patients with lower plasma viral load, and higher CD4 and CD8 percentages at baseline, and an undetectable viral load after treatment were more likely to achieve an undetectable seminal viral load after six months of anti-HIV therapy. Although people taking triple combinations were more likely to have undetectable seminal viral load than those on dual therapy, this difference was not significant.
Seminal viral load suppression was strongly associated with reported adherence, with patients saying that they took at least 80% of their doses being twelve times more likely to achieve a viral load below 400 copies/ml in their semen than less adherent patients.
Twenty patients were found to have a persistently detectable HIV viral load after six months of treatment, with an average seminal viral load of 11,000 copies/ml and plasma viral load of 22,000 copies. All the patients achieving an undetectable seminal viral load had an undetectable plasma viral load.
In multivariate analysis, being adherent to therapy, using a triple combination, and having a higher CD4 percentage were all found to be statistically associated with achieving an undetectable seminal viral load after six months of treatment.
The investigators comment, “lack of adherence to [antiretroviral therapy] was the most important factor in this study contributing to persistent shedding in semen at 6 months.” They argue that their findings have implications not only for the clinical outcome of patients but for public health, noting “the frequency of high blood...and high seminal viral loads among persistent shedders is worrisome, because data from other settings suggest that the risk of transmission could be substantial and that the presence of drug-resistant HIV in at least some of our patients was likely.”
Most patients in this study were taking a standard of treatment which would be considered suboptimal in countries with ready access to anti-HIV therapy, and were considered adherent at a level associated with virological failure. Nevertheless the study does demonstrate a reduced risk of sexual transmission in adherent patients, and could therefore have value for the development of HIV prevention and adherence support strategies, both in settings where HAART is readily available and in resource limited setting able to offer a lesser standard of care.
Further information on this website
Gonorrhoea is STI most likely to cause HIV rebound in semen of HAART patients - News story
Adherence - Factsheet
Viral load - Overview
Viral load and CD4 - Booklet in the information for HIV-positive people series
Barroso PF et al. Adherence to antiretroviral therapy and persistence of HIV RNA in semen. JAIDS 32: 435-440, 2003.