Low incidence of adverse drug reactions associated with generic-equivalent antiretroviral product substitutions in a publicly-funded HIV treatment program


BACKGROUND: Generic antiretrovirals (ARVs) provide low-cost alternatives to brand-name products. In British Columbia Canada, persons living with HIV (PLWH) receive ARVs free-of-charge through a publicly-funded HIV Drug Treatment Program (DTP). Brand-name products are automatically switched to available generic equivalents in accordance with Health Ministry policies. We describe the incidence and type of adverse reactions attributed to generic ARVs (generic product substitution issues, 'PSIs') reported to DTP Pharmacovigilance.
METHODS: We included PLWH age '¥19 years who received '¥1 commonly used generic ARV between 01-Jun-2017 and 30-Jun-2021: abacavir-lamivudine (ABC-3TC), emtricitabine-tenofovir disoproxil fumarate (FTC-TDF), efavirenz-FTC-TDF (EFV-FTC-TDF), atazanavir or darunavir. Manufacturer-specific generics were categorized as 'generic-1' (brand-to-generic transition) and 'generic-2' (generic-1-to-2 transition). All data were extracted from DTP databases. Antiretroviral use and PSIs were summarized monthly. PSI incidence proportion (95% confidence interval, [95%CI]) and symptoms were described during the first year following each generic transition (product rollout) date. After pooling across products, a logistic regression model (using generalized estimating equations) compared PSI incidence for generic-2 versus generic-1.
RESULTS: Between 01-Jun-2017 and 30-Jun-2021, 5560/8842 (63%) of ARV-treated PLWH received generic ARVs, of whom 5421/5560 (98%) received '¥1 of the generics studied. Of N=5421, 83% were male, median age 52 (Q1-Q3=43-58) years. Overall, 27% received one, 40% two, and 33% three or more different generics.
Figure 1a-1e shows longitudinal ARV usage, PSI frequency, and first-year PSI incidence, which was <1% for most generics. Of 93 PSIs, 71/93 (76%) were reported '¤1 year post-generic transition date. Common symptoms included mild-moderate gastrointestinal, central nervous system (predominantly efavirenz-related), dermatologic, and general (unwellness/ malaise) effects.
Pooled analysis of ABC-3TC, FTC-TDF and EFV-FTC-TDF showed significantly lower first-year PSI incidence for generic-2 (0.55%, 95%CI=0.31-0.78%) versus generic-1 (0.98%, 95%CI=0.69-1.27%), p=0.029, suggesting fewer PSIs with generic-to-generic versus initial brand-to-generic transitions.

CONCLUSIONS: We report a low incidence of adverse drug reactions attributed to ARV generic product substitution.

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