Efavirenz-associated gynaecomastia reported to the national HIV and TB healthcare workers hotline in South Africa

Efavirenz-associated gynaecomastia (benign proliferation of glanular breast tissue in males) has been frequently reported to the South African national HIV and TB healthcare workers hotline. Results from a study conducted to look at this phenomenon were presented at the 2014 Southern African Clinicians Society Conference.

Christine Njuguna from the Division of Clinical Pharmacology, University of Cape Town showed data from the study, which included likely gynaecomastia cases reported to the hotline between 1 June 2013 and 31 July 2014.

Fifty-one cases were reported, which made up 11% of 469 adverse event queries during the study period. The mean age of the men and boys was 34 years (SD +/- 12); 86% were adults >18 years and the remaining 14% were adolescents aged 10-17 years. Overall, the mean baseline CD4 count was 188 cells/mm3 (SD +/-94) and 51% of the cohort was virally suppressed <50 copies/mL. Onset of gynaecomastia occurred and a median of 15 months (IQR 6-41) after ART initiation.

All cases were receiving efavirenz-based regimens. Additional other drugs were suspected in 31% of cases: isoniazid (n=12), d4T (n=5) and amlodipine (n=1).

Out of 51 cases, 35 (16%) were followed up for a median of 4 months (IQR 1-6). Testosterone was measured at follow up in 25/35 (71%) of which 19 (76%) had normal and 2 (8%) had low levels. Efavirenz was switched in 29 (82%) cases, of which 16 had normal testosterone levels. The majority (n=27) switched to nevirapine and two cases switched to lopinavir/ritonavir.

Overall outcomes in 35 men and boys with follow up were: 7 (20%) resolved, 14 (40%) improved, 3 (8%) were unchanged and 11 (31%) unknown. The median time to improvement was 3 months (IQR 2-4, range 1-8).

In conclusion Dr Njuguna noted that efavirenz-associated gynaecomastia was frequently reported to the hotline. Most cases had prolonged efavirenz exposure and normal testosterone. Seven cases were in adolescents for which data are sparse.

She suggested that prospective studies are needed to look at: incidence and risk factors, the proportion associated with hypogonadism, optimal management (continue or stop efavirenz), including in puberty.