Breast enlargement or gynaecomastia has been reported since 1998 in men and women receiving antiretroviral therapy. Although case reports are rare, its prevalence has not been established, and its causes are unclear. Whilst some researchers believe it is a side-effect of antiretroviral therapy, and possibly a manifestation of lipodystrophy, others believe it has more complex causes.

Researchers from Boston and Seattle reported on the characteristics of 13 cases seen during an 18-month period at two clinics. Although nine men had developed gynaecomastia, mainly characterised by enlargement and tenderness on one side of the chest, three patients had developed lymphoma. The researchers warned that cases of breast enlargement should not be dismissed as drug side-effects, and also pointed out that gynaecomastia can also be caused by other medications. Two of the individuals who developed gynaecomastia were not receiving HIV treatment at the time of diagnosis, three were receiving treatment with drugs known to cause gynaecomastia and three were long-term users of marijuana. One case combined all three of these features. Only one out of 13 patients had low testosterone levels (hypogonadism).

A Spanish case-control study identified 40 cases of confirmed gynaecomastia and matched these individuals with randomly selected HIV-positive patients. The researchers found a prevalence of 1.8% in their cohort. Multivariate analysis found that co-infection with hepatitis C virus, low testosterone levels, fat loss, and current use of d4T or efavirenz (Sustiva) remained independently associated with gynaecomastia (Biglia 2004).

Despite these reservations, a recent observational study has identified efavirenz use as a possible cause of gynaecomastia in five patients. In all five cases, the condition regressed after discontinuation of efavirenz. The study's authors suggest that immune reconstitution or elevated levels of the female sex hormone oestradiol due to inhibition of cytochrome P450 may be the cause of the condition (Jover 2004). Similarly, a prospective case-control study of gynaecomastia in over 1300 men taking antiretroviral therapy found a significant association between breast enlargement and efavirenz or ddI (didanosine, Videx / VidexEC) use. This was correlated with low levels of testosterone (Mira 2004).

References

Biglia A et al. Gynecomastia among HIV-infected patients is associated with hypogonadism: a case-control study. Clin Infect Dis 39: 1514-1519, 2004.

Evans DL et al. Breast enlargement in 13 men who were seropositive for human immunodeficiency virus. Clinical Infectious Diseases 35: online edition, 2002.

Jover F et al. Efavirenz-associated gynecomastia: five cases and review of the literature. Breast J 10: 244-246, 2004.

Mira JA et al. Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: association with efavirenz and didanosine treatment. Antivir Ther 9: 511-517, 2004.