Breast enlargement in Malawian males on the standard first line antiretroviral therapy regimen: Case reports and review of the literature

Abstract

1. A 35-year-old man was referred to Zomba Central Hospital in June 2014 from a health center with a presenting complaint of enlarged breasts. This had started gradually, approximately six months prior. He did not experience any pain or discharge from his nipples. He had no other complaints and felt generally healthy. In early 2013 he had been concomitantly diagnosed with pulmonary tuberculosis and HIV infection and was started on cotrimoxazole prophylaxis and antiretroviral therapy (ART) with tenofovir, lamivudine, and efavirenz, which is the standard first-line adult ART regimen, known in Malawi as regimen 5A. At that point, he had WHO clinical stage III HIV disease; a CD4 count was not done. There was no further relevant past medical history. He looked healthy and had normal vital signs. The rest of the physical examination was normal except for bilateral, symmetrical, elastic, and concentric swelling of the breasts, without discrete nodules, skin changes, or lymphadenopathy in the axillae and neck. There were no features of lipodystrophy and no stigmata of chronic liver disease. The genital examination was normal, without palpable abnormalities of the normal-sized testes. Upon laboratory investigation, his CD4 count was 130 cells/µL and a full blood count was normal apart from the presence of macrocytosis. Liver enzymes were unremarkable.2. In October 2014, we saw a 56-year-old male who presented with development of painless bilateral breast enlargement. This had started in May 2014, followed by spontaneous regression and then subsequent worsening from August 2014. The left breast was more conspicuously affected. He also mentioned experiencing weight loss but had no other symptoms. He was diagnosed with HIV infection in 2005 and started on ART in 2008 due to a low CD4 count of 83 cells/µL. While on his first ART regimen-stavudine, lamivudine, and nevirapine-he experienced progressive peripheral neuropathy and was eventually switched to a regimen of zidovudine, lamivudine, and nevirapine, after which his CD4 count was 409 cells/µL and plasma HIV-1 RNA was undetectable. Six months later, in January 2010, he developed severe anaemia, secondary to zidovudine, and his ART regimen was changed again, this time to tenofovir, lamivudine, and efavirenz (regimen 5A). He had no other significant past medical history and the only medications he used were cotrimoxazole prophylaxis and tenofovir, lamivudine, and efavirenz. Bilateral breast enlargement (left more than right, see Figure 1) was the only abnormality found on physical examination, with the same pertinent negative findings as in the first case presented in this report.

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

“…This finding is similar to other case series where efavirenz was discontinued [12, 13, 15], but it is noteworthy that other studies have reported improvement in patients, despite continuation of efavirenz [4, 8, 9]. Time to complete resolution was slow in our case series and was comparable to other studies that have reported a resolution time ranging from two to nine months [4, 6, 8, 12, 15].…”

“…A small case series from Nigeria reported on six patients with efavirenz-associated gynaecomastia, all of which resolved after withdrawal of efavirenz [12]. Two cases of efavirenz-associated gynaecomastia were reported from Malawi, both of which improved after switching efavirenz to nevirapine [13]. …”

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis

“…4 This case report builds upon these prior findings with the description of two additional cases of gynaecomastia from Mozambique. The two males infected with HIV were on stable ART containing EFV.…”

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

“…6 In several other studies associations between gynaecomazia and specific antiretroviral drugs, including stavudine and efavirenz, have been reported. 5 In most cases, gynaecomastia cases reported occurred after prolonged efavirenz exposure. Efavirenz is known to be associated with gynaecomazia, as when switched from efavirenz, gynaecomazia improved/resolved in the majority.…”

“…Physiological gynaecomazia is self-limiting and occurs in newborns, adolescents, and the elderly. 5 The prevalence of asymptomatic gynaecomazia is 60 to 90% in neonates, 50 to 60% in adolescents, and up to 70% in men aged 50 to 69 years. 3 It has to be distinguished from pseudogynecomastia and lipomastia, which are both forms of fat accumulation in the breasts.…”