A 54-year-old male, diagnosed with HIV-1 infection 8 years earlier, was well controlled on Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil 245 mg) with CD4 count 370 cells/mm3 and viral load <40 copies/ml presented with fever, weight loss and shortness of breath. Chest imaging found a large left pleural effusion with left lower lobe consolidation. Fully sensitive M. tuberculosis was isolated from pleural specimens. He responded to standard anti-tuberculosis treatment (rifampicin, isoniazid, pyrazinamide and ethambutol). Atripla was continued with additional efavirenz 200 mg o.d. to overcome predicted rifampicin-efavirenz drug interaction. After 2 months, he developed marked reduction in libido with erectile dysfunction. Investigations found serum total testosterone 11 nmol/l, SHBG 170 nmol/l, calculated free testosterone 60 pmol/l, LH 14 IU/ml and FSH 15 IU/ml. Efavirenz has a direct oestrogenic effect by modulating oestrogen receptors [], and this effect may have been exacerbated by SHBG elevation (HIV infection, anti-tuberculosis treatment and ART) reducing free testosterone concentrations, despite normal total levels. After additional efavirenz was discontinued, SHBG returned to normal and his clinical symptoms fully resolved.
A 57-year-old HIV-infected man who attended for routine HIV clinical review described increased fatigue, reduced libido and erectile dysfunction unresponsive to phosphodiesterase-5 inhibitor use. He had stable type 2 diabetes mellitus (controlled by metformin 1 g b.d). He presented 2 years earlier with pulmonary tuberculosis and HIV-1 infection with nadir CD4 count 50 cells/mm3 and viral load >100,000 copies/ml. His HIV infection was well controlled (CD4 540 cells/mm3, viral load <40 copies/ml) by Maraviroc 300 mg b.d. and Kivexa (abacavir 600mg/lamivudine 300 mg o.d.). Physical and genital examination was normal. Investigations included early morning total testosterone 6.2 nmol/l (normal range 9.4–37 nmol/l), calculated free testosterone 142 pmol/l (normal range 174–729 pmol/l), LH 16 IU/ml (normal range 1–9 IU/ml), FSH 24 IU/ml (normal range 1–10 IU/ml) and SHBG 22 nmol/l (normal range 15–40 nmol/l). A diagnosis of primary hypogonadism was made. Topical testosterone treatment (Testogel, one sachet per day) was initiated with resolution of symptoms.