Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa

Abstract

BackgroundGynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa.MethodsWe identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes.ResultsWe received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%).ConclusionsGynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.

Adult antiretroviral therapy guidelines 2017

“…Resolution of gynaecomastia is generally slow, taking months and may be incomplete in a small percentage. 67 It is, therefore, important to manage the expectations of the patient in this regard.…”

Gynaecomazia in a HIV, Hepatitis B and C affected middle aged male: a case report

“…2,3 In contrast, hypogonadism among HIV-infected adult men seems to be a condition that has been underestimated in frequency, and it was an independent factor associated with gynaecomazia. 8 In the reported case, patient was exposed to numerous risk factors like drugs, HCV infection and hypogonadism. He took anti-tubercular drugs twelve years before the onset of symptoms and taking Efavirenz based ART for seven years before he noticed breast swelling, which differs from most of the studies.…”

“…Two other hypothesized mechanisms have been suggested for ART-associated gynaecomazia are: a) immune restoration may increase breast tissue oestrogen availability, and b) efavirenz has been shown to increase the area under the curve of ethinyl oestradiol by at least 37%, thereby elevating the oestrogen-androgen ratio. 7,8 Opportunistic infection, lymphoma, Kaposi's sarcoma and pseudoangiomatous stromal hyperplasia (PASH) form part of the further differential diagnosis. 6 It was also found that gynaecomazia among HIV-infected patients is related to hypogonadism, rather than to an adverse effect of antiretroviral drugs, while other study report that lipoatrophy and chronic hepatitis C are independent factors associated with gynaecomazia.…”

Efavirinz induced gynecomastia: a case report

“…11 Two other hypothesized mechanisms have been suggested for ART-associated gynecomastia: immune restoration may increase breast tissue oestrogen availability, and efavirenz has been shown to increase the area under the curve of ethinyloestradiol by at least 37%, thereby elevating the oestrogen-androgen ratio. 12 The introduction of highly active antiretroviral therapy (HAART) in developed countries in the late 90s has been associated with a remarkable decrease in AIDS-related mortality. This decrease in mortality has changed the perspective of HIV infection from that of a rapidly fatal to a chronic manageable infection.…”