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Two-drug HIV therapy just as effective as three-drug therapy
Keith Alcorn, 2016-10-25 09:30:00

Simplification of an antiretroviral treatment to a boosted protease inhibitor and the nucleoside analogue lamivudine (a dual regimen) is highly effective in people switching from a stable three-drug regimen, researchers reported on Monday at the International Congress on Drug Therapy in HIV Infection in Glasgow.

Boosted protease inhibitors combined with lamivudine have the potential to realty reduce the cost of long-term treatment as boosted protease inhibitors come off patent over the next two years in higher-income countries. These regimens may also reduce the risk of any long-term side-effects associated with triple-drug therapy, most notably the bone and kidney toxicities caused by tenofovir.

The ATLAS-M study was a multi-centre, open-label randomised study conducted in Italy lasting 96 weeks. It was designed to explore the non-inferiority of a simplified regimen of atazanavir/ritonavir plus lamivudine compared to atazanavir/ritonavir plus two nucleoside reverse transcriptase inhibitors. To be eligible for recruitment, patients were required to taking stable ART with a viral load below 50 copies/ml for at least three months and a CD4 count above 200 cells/mm3 for a minimum of six months.

The study population comprised 266 people with a median age of 44 years. The two study arms were evenly matched in baseline characteristics, with median CD4 cell count of approximately 620 cells/mm3, a median of 23 months of prior treatment with viral load suppressed below 50 copies/ml, 84% male in the dual-regimen arm and 75% male in the triple-regimen arm. 78% in the dual-regimen arm and 83.5% in the triple-regimen arm were taking tenofovir prior to randomization.

At baseline, participants were randomised to atazanavir/ritonavir with lamivudine (dual therapy) or to continue the baseline three-drug regimen. The primary outcome measured in the study was treatment failure at 96 weeks, with participants defined as a case of treatment failure if they had stopped treatment for any reason.

After 48 weeks, patients taking dual therapy had a lower rate of treatment failure compared to individuals who remained on triple therapy (89.5% vs 79.7%) and this difference persisted at week 96 (77.4% vs 65.4%). The study found that the dual regimen was statistically superior to the triple regimen, and that this difference was driven largely by a difference in virological failure rates between the two arms (although that difference in itself was not statistically significant) (1.2% in the dual arm vs 6.8% in the triple arm, p =0.060). Potentially treatment-related adverse events were also somewhat more frequent in the triple-regimen arm, and this difference appeared to have been driven by five treatment discontinuations due to renal colic, probably attributable to atazanavir, in the triple regimen arm, compared with two in the dual therapy arm.

Renal colic, urinary tract and bone adverse events were more frequent in the triple-regimen arm, while respiratory tract and skin adverse events were more frequent in the dual-regimen arm, but overall the rate of clinical adverse events was similar between the two study arms.

Modest but statistically significant increases in LDL and HDL cholesterol and triglycerides occurred by week 96 in the dual-regimen arm (treatment with tenofovir is associated with lower cholesterol levels) but the overall ratio of HDL to total cholesterol did not change significantly. Patients taking the simplified combination had a higher frequency of elevated triglycerides (8% vs. 2%, p = 0.027), hyperbilirubinemia (60% vs. 36%, p = 0.001), as well as a greater increase in total cholesterol (+15 vs. +0mg/dl, p = 0.005) and HDL cholesterol (+5 vs + 0mg/dl, p = 0.002).

Kidney function improved modestly in the dual-regimen arm by week 96, as measured by eGFR (+5 ml/min/1.73m2), and declined in the triple-regimen arm before returning almost to baseline by week 96 in the triple-regimen arm.