An updated, massive analysis of prospective first-line HIV treatment studies found that more than 20% of participants who initiated antiretroviral therapy in this decade failed treatment within 144 weeks, a rate much higher than generally seen in randomized trials, according to findings published in AIDS.
The new analysis updates prior research by including studies conducted between 2013 and 2017; in total, the database now comprises 181 studies and 77,999 participants spanning roughly 23 years.
The current examination focused specifically on individuals who started HIV treatment through a prospective study (believed to be a more accurate indication of "real-world" efficacy than individual, randomized trials) since 2010, exploring the frequency and correlates of failure after 48 weeks, 96 weeks, and 144 weeks.
Despite the sobering finding of overall failure rates still exceeding 20% in this decade, the researchers noted that efficacy is on the rise historically, and appears to be highest among the newest medications. Integrase inhibitor-based therapy, for instance, yielded a 48-week efficacy rate of about 88%, surpassing boosted protease inhibitor-based therapy (73%) and NNRTI-based therapy (71%).
In addition, most of the reported treatment failures in analyzed studies were due to people withdrawing or being lost to follow up, not an observed lack of efficacy. There was little data on why participants dropped out. Collecting standardized socioeconomic variables in clinical trials may help elucidate these reasons, study authors noted.
Based on cumulative efficacy data, the authors recommended that zidovudine (AZT, Retrovir) and efavirenz (Sustiva, Stocrin) no longer be listed as part of preferred first-line regimens for resource-limited settings; that there be greater promotion of genotyping before starting antiretroviral therapy; and that a clinical trial be conducted comparing emtricitabine (FTC, Emtriva) to lamivudine (3TC, Epivir) when either is taken in combination with tenofovir disoproxil fumarate and efavirenz. Furthermore, phase 4 studies should include longer follow-up periods and a four-drug initial regimen should be evaluated for people starting treatment at high viral loads, they advocated.