Ritonavir most strongly linked to male sexual dysfunction

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An American study has found that men treated with protease inhibitors are more likely to experience sexual dysfunction.

A retrospective examination conducted by investigators at Harvard Vanguard Medical Associates, of the medical records of 254 men treated with a protease inhibitor between 1993 and 1998, found that almost a third had reported sexual problems. The study is published in the May 2002 edition of the Journal of Acquired Immune Deficiency Syndromes.

The study sample had an average CD4 count below 200 cells/mm3 and a viral load above 10,000 copies/ml when first given a protease inhibitor. Indinavir (Crixivan) was the most commonly presecribed protease inhibitor (62% of cohort members), followed by nelfinavir (Viracept) (46%), ritonavir (Norvir) (46%) and saquinavir hard or soft gel (Invirase and Fortovase) (41%). Ritonavir and saquinavir were usually prescribed together (31% of the cohort).


statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 


A mental health problem causing long-lasting low mood that interferes with everyday life.


Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

The most frequently used NRTIs were 3TC (lamivudine, Epivir), d4T (stavudine, Zerit) and AZT (zidovudine, Retrovir). Between 1993 and 1998, NNRTIs were used less frequently than today, with 27% provided with a HAART regimen containing this class of drug.

A total of 80 patients (32%) reported at least one incident of sexual dysfunction during the period of the review. Of protease inhibitors, ritonavir was most associated with erectile dysfunction. The frequency with which sexual dysfunction occurred in people treated with indinavir, nelfinavir and saquinavir was not statistically significant.

When the association between treatment with NRTIs and sexual dysfunction was examined, only 3TC was seen to have a statistically significant relationship. No association with sexual dysfunction and NNRTIs was detected by researchers.

The results were adjusted for factors which can independently cause sexual problems, including age, a low CD4 count, depression, hypertension, alcoholism and diabetes. Nevertheless, treatment with protease inhibitors was still seen to be significantly associated with sexual dysfunction (Hazard Ratio = 2.22, p=.007).

By contrast, once these factors had been taken into account, the link between 3TC and sexual problems diminished.

When available, a comparison of testosterone and other hormonal levels between people who had reported sexual dysfunction and those with normal sexual function showed that this was not a factor. Nor was anabolic steroid use found to be significant.

The researchers conclude that their analysis shows a link between protease inhibitors, particularly ritonavir and sexual dysfunction. However, they acknowledge limitations with their study, not least that it is a retrospective analysis. The investigators called for a prospective study and further research into the association between 3TC and erectile problems.


Colson AE et al. Male sexual dysfunction associated with antiretroviral therapy. JAIDS 30 (1):27-32, 2002.