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

BACKGROUND: Gynaecomastia 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. METHODS: We 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. RESULTS: We 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%). CONCLUSIONS: Gynaecomastia 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.

South African healthcare workers' knowledge of dolutegravir's drug-drug interactions in the first year of its rollout: a cross-sectional online survey.

INTRODUCTION: In December 2019, dolutegravir-based treatment was recommended as first-line antiretroviral therapy (ART) in South Africa. Dolutegravir has clinically significant interactions with several commonly used drugs, such as rifampicin, metformin and cation-containing medicines. National guidelines detail these interactions and how to manage them. While previous international studies have shown low healthcare worker knowledge of drug-drug interactions, there is a paucity of information on antiretroviral interaction knowledge in the South African setting, where much ART is nurse-led. The study aimed to determine this knowledge and to describe which variables were associated with gaps in knowledge. METHODS: An anonymous online survey of healthcare workers in the field of HIV was conducted in August/September 2020. The survey was designed, tested and piloted, and included sections on demographics, guideline access and training, interaction knowledge, counselling and the effect of COVID-19. Dissemination was via e-mail and social media (convenience sampling). Descriptive and inferential analysis was done using proportions and the 95% confidence interval to determine relationships between independent and dependent variables. Research ethics approval was obtained from the University of Cape Town's Human Research Ethics Committee (HREC Ref: 357/2020). RESULTS AND DISCUSSION: In total, 1950 survey responses were included in the analysis - 47.1% nurses, 35.8% doctors and 8.9% pharmacists. When asked whether they were aware that dolutegravir has interactions, 70% said yes, 13.9% said no and 16.1% did not answer. Knowledge of specific interactions and the dosing changes needed was low with a wide range between different drugs: 79.7% knew to double the dolutegravir dose with rifampicin, but with calcium, 5.1% picked both correct dosing options and 33.7% picked one of the two correct options. Access to guidelines and training were positively associated with drug interaction knowledge. CONCLUSIONS: There are gaps in the awareness and knowledge of dolutegravir interactions and how to adjust dosing among South African healthcare workers.

The impact of the National HIV Health Care Worker Hotline on patient care in South Africa.

BACKGROUND: South Africa has a huge burden of illness due to HIV infection. Many health care workers managing HIV infected patients, particularly those in rural areas and primary care health facilities, have minimal access to information resources and to advice and support from experienced clinicians. The Medicines Information Centre, based in the Division of Clinical Pharmacology at the University of Cape Town, has been running the National HIV Health Care Worker (HCW) Hotline since 2008, providing free information for HIV treatment-related queries via telephone, fax and e-mail. RESULTS: A questionnaire-based study showed that 224 (44%) of the 511 calls that were received by the hotline during the 2-month study period were patient-specific. Ninety-four completed questionnaires were included in the analysis. Of these, 72 (77%) were from doctors, 13 (14%) from pharmacists and 9 (10%) from nurses. 96% of the callers surveyed took an action based on the advice received from the National HIV HCW Hotline. The majority of actions concerned the start, dose adaption, change, or discontinuation of medicines. Less frequent actions taken were adherence and lifestyle counselling, further investigations, referring or admission of patients. CONCLUSIONS: The information provided by the National HIV HCW Hotline on patient-specific requests has a direct impact on the management of patients.

Adverse Drug Reactions Reported to a National HIV & Tuberculosis Health Care Worker Hotline in South Africa: Description and Prospective Follow-Up of Reports.

INTRODUCTION: The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. METHODS: We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. RESULTS: We received 772 ADR reports, of which 87/772 (11.3%) were classified as certain, 176/772 (22.8%) as probable, 361/772 (46.8%) as possible, and 148/772 (19.2%) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6%), 87/624 (13.9%), and 77/624 (12.3%), respectively. The ADR was severe in 27.3% of rashes, 36.4% of kidney injury reports and 88.5% of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti-tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3%) improved, 9 (2.3%) had complete resolution, 32 (8.4%) remained unchanged, 6 (1.6%) deteriorated, 10 (2.6%) died and 72 (18.8%) had unknown outcome. Advice provided was followed in 93.2% of these cases. Of 223 ADRs with preventability data, 40 (17.9%) were preventable. CONCLUSION: Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority.