An analysis of 440 people switched to generic antiretroviral drugs at an Italian clinic and a matched cohort of patients who remained on their branded medication has found no evidence of generic drugs being less effective or causing more side-effects, Nicola Gianotti and colleagues report in an article recently published in PLOS ONE.
In many high-income countries, health services are under increasing financial pressures. At the same time, the patents on several antiretroviral drugs have expired and cheaper, generic versions of the same drugs have been made available. Doctors and pharmacists are expected to use generic drugs when possible as they generally work as well as branded drugs, and the money saved can pay for other treatments and services. (For more information on generic medicines, click here).
Nonetheless, some people question the quality and efficacy of generic drugs. Generic manufacturers must prove that their products have the same pharmacokinetic properties as the original formulation, with comparable drug levels of the active ingredients, but are not required to run clinical trials with head-to-head comparisons of generic and branded medicines. Furthermore, small differences in a medicine’s non-active ingredients and manufacturing processes could potentially have an impact for a minority of patients.
Previous studies on generic antiretrovirals have all been conducted in low or middle-income countries. Moreover, only one previous study has compared outcomes between patients prescribed branded and generic drugs – in an observational cohort of almost 15,000 Zambian patients beginning HIV treatment, half received branded zidovudine and half generic zidovudine. There were no differences in mortality, weight gain or CD4 response, but virological response was not assessed.
Switching to generics in Italy
The study comes from a single clinic in Milan, Italy. Beginning in September 2014, all patients who were stable on branded lamivudine (Epivir), zidovudine/lamivudine (Combivir) or efavirenz (Sustiva)were switched to a generic version of the same drug.
The researchers compared outcomes for this group with a matched cohort of patients at the same clinic who did not switch drugs. It is important to note that this control group is not made up of patients taking the same drugs (lamivudine, zidovudine/lamivudine or efavirenz). Those in the control group were taking other antiretrovirals which were not available in generic formulations. However, the control group was well matched in other respects, including demographics and previous experience of treatment.
Amongst the 440 switchers and 440 non-switchers, three-quarters were men, most were in their late forties or their fifties, and the median time since HIV diagnosis was 19 years. All participants had an undetectable viral load. Their median CD4 cell count was around 700, their median lowest ever CD4 cell count was a little over 200 and over a quarter had antibodies to hepatitis C.
As noted, there were differences in terms of drugs taken. Whereas 40% of switchers were taking protease inhibitor-based dual therapy, this was the case for just 8% of non-switchers. Only 60% of switchers were taking triple therapy, compared to 92% of non-switchers.
The researchers assessed outcomes after an average of 15 months of follow-up. Key outcomes were virological failure and treatment discontinuation.
Concerning virological failure (confirmed viral load over 50 copies/ml), there were four cases in switchers and ten in non-switchers. Virological failure was therefore less common in those taking generics and the difference was statistically significant.
In order to look at virological outcomes in more detail, the researchers also looked at viral blips (single viral load measures over 50 copies/ml) and time spent with residual viremia (a viral load below 50 copies/ml that remained detectable on the Abbot Real-Time PCR; this has been associated with a higher risk of subsequent virological failure). There were no statistically significant differences – viral blips occurred in 32 switchers and 33 non-switchers; time spent with residual viremia was 29% and 30% respectively.
Treatment discontinuation (any change in drug regimen) occurred in 118 (27%) of switchers and 128 (29%) of non-switchers. In both groups, the key reasons for changing drugs were side-effects, simplifying treatment and drug-drug interactions. The rate of treatment discontinuation is high but comparable to other cohorts of Italian people living with HIV.
Because of the important differences in drug regimen between the two groups, the researchers also conducted a sensitivity analysis which only included patients treated with standard triple therapy. Virological failure was less common in those switching to generics. Treatment discontinuation also appeared to be less common, but the difference was not statistically significant.
“In this observational study we compared patients switched to generic antiretrovirals with a matched population who continued taking branded drugs and we did not find evidence of reduced efficacy or increased toxicity related to switch from branded to generic antiretroviral drugs,” the authors say. Moreover, their findings on virological failure would suggest that “the virological potency of these generic formulations is at least as high as that of the patent drugs”.