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 51-year-old male with stable HIV infection (current CD4 350 cells/mm3, viral load <40 copies/ml) managed on Triumeq (dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg) had been diagnosed 9 years earlier when presenting with disseminated tuberculosis (sites of involvement: pulmonary, renal, meningeal). He also had sero-positive rheumatoid arthritis. He described ongoing lethargy, fatigue and loss of muscle strength. Serum total testosterone was 2.1 nmol/l, calculated free testosterone 46.1 pmol/l, LH 5 IU/l, FSH 10 IU/l, SHBG 21 nmol/l, thyroxine 13 pmol/l (normal range 9–25 pmol/l), cortisol 394 nmol/l (normal range 138–620 nmol/l) and prolactin 74 mIU/l (normal range 50–400 mIU/l). Magnetic resonance imaging (MRI) of the pituitary found a low volume pituitary gland with hypointense parenchyma consistent with healed granulomatous lesion (Fig. ). Symptoms resolved following intramuscular testosterone replacement.