DISCUSSION
Antiretrovirals are essential lifelong medications for managing HIV, and it’s crucial to understand the associated drug interactions (DDIs) to improve treatment outcomes and safety. Injectable antiretrovirals can reduce DDI risks by avoiding the gastrointestinal route, but caution is necessary for those metabolized by CYP3A4 in the liver(8). In our case, the patient is on injectable antiretroviral therapy containing rilpivirine and also requires medical treatment for gynecomastia. Combining drugs that induce CYP3A4 activity with antiretrovirals primarily metabolized by CYP3A4 (such as protease inhibitors (PIs) or NNRTIs like rilpivirine) can decrease their levels, potentially leading to viral failure or drug resistance.
Treatment options for gynecomastia include: reassurance or observation, discontinuation of the causative agents and addressing underlying disease. Medical therapies include: estrogen antagonists as first line and alternatively a weak androgen or an aromatase inhibitor(4,5,7). Although tamoxifen is not licensed for treatment of gynecomastia, it is widely used and recommended by several guidelines with reports of good response1. It’s use in gynecomastia among the general population and people living with HIV has been described previously(9,10). Tamoxifen is an estrogen antagonist and undergoes wide hepatic metabolism involving some isoforms of the cytochromes. It induces the activity of CYP3A4 both in vivo and in vitro(6). According to the HIV liverpool drug-drug interaction checker, when tamoxifen is taken with rilpivirine, this induction may lead to a decrease in the exposure of rilpivirine as well as other antiretrovirals primarily metabolized by CYP3A4.
The European Academy of Andrology (EAA) guidelines discourage the use of selective estrogen receptor modulators, aromatase inhibitors and dihydrotestosterone due to lack of quality data(4). However, the association of breast surgery and Nottinghamshire Area Prescribing Committee (APC) NHS permits the use of aromatase inhibitors (anastrozole) if tamoxifen is not well-tolerated or as a secondary option if anastrozole shows no response(7,11). Anastrozole is a selective non-steroidal aromatase inhibitor that hinders the activity of the enzyme CYP19A1 (aromatase), responsible for converting androgens into estrogens(12). It has been used in chemoprevention and adjuvant therapy for post-menopausal women at risk of breast cancer(13,14), with notable side effects like osteoporosis, nausea, and hot flashes(13–15) and for gynecomastia in adolescents(16,17). Despite the lack of available studies on the co-administration of anastrozole with most antiretroviral agents, the likelihood of a clinically significant interaction is low. This is primarily attributed to anastrozole’s inhibitory nature, which reduces the potential for diminishing the concentration of antiretroviral drugs(6).
Our case report offers a contribution on treatment of gynecomastia using anastrozole and explains the possible interactions with antiretrovirals. The increasing use of injectable antiretroviral therapy in the near future leads us to find an alternative to tamoxifen to avoid drug drug interactions with rilpivirine or other antiretroviral therapy as well as other antiretrovirals majorly metabolized by CYP3A4.