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HIV Glasgow: Darunavir/Ritonavir + Lamivudine Matches Triple-Drug HIV Therapy

Simplifying antiretroviral therapy to a 2-drug combination of lamivudine plus the protease inhibitor darunavir (Prezista) boosted by ritonavir is just as effective as a 3-drug regimen in people with suppressed viral load, Spanish investigators reported at the International Congress on Drug Therapy in HIV infection (HIV Glasgow) last month in Glasgow.

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Simplifying antiretroviral therapy so that a boosted protease inhibitor or an integrase inhibitor is taken with lamivudine holds several attractions:

• The simplified regimen may reduce the risk of toxicities potentially associated with use of a second nucleoside or nucleotide analog: cardiovascular disease in the case of abacavir, and kidney injury or bone loss in the case of tenofovir. Lamivudine has few side effects and is well tolerated by the vast majority of people.
• Lamivudine does not interact with drugs used to treat other conditions, reducing the potential for problematic drug interactions between an antiretroviral regimen and other medications, which is especially important for older people with HIV.
• The simplified regimen is less costly because lamivudine is available in a cheap generic formulation.
• Virological rebound after failure of the simplified regimen will not result in cross-resistance to tenofovir, thus preserving this drug as a future option. Rebounding virus may also remain sensitive to abacavir, although this depends on previous treatment history.

Pilot studies presented at previous conferences have shown that regimens combining the boosted protease inhibitor lopinavir/ritonavir (Kaletra) or the integrase inhibitor dolutegravir (Tivicay) with lamivudine are just as effective as 3-drug regimens in previously untreated people.

Studies presented earlier in the week at HIV Glasgow showed that simplified maintenance regimens for virally suppressed patients were non-inferior to 3-drug treatment, both for those without any history of virological failure and for those already taking second-line treatment.

Previous attempts to simplify therapy using monotherapy with a single boosted protease inhibitor have shown that approach to be less durable than 3-drug treatment.

The DUAL Study

The DUAL study, conducted in Spain, tested simplification of a regimen containing darunavir/ritonavir, the only recommended boosted protease inhibitor option in European and U.S. HIV treatment guidelines.

The DUAL study randomized 249 people with undetectable viral load on a regimen of darunavir/ritonavir plus either tenofovir/emtricitabine (Truvada) or abacavir/lamivudine (Epzicom) either to continue taking their existing regimen or to switch to a simplified regimen of darunavir/ritonavir plus lamivudine alone. All regimens were dosed once daily.

The study recruited people with no evidence of resistance to darunavir or lamivudine, who had fully suppressed viral load for at least 6 months on a regimen of darunavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine. Three-quarters of participants (75%) were taking tenofovir/emtricitabine and 25% were taking abacavir/lamivudine at the time of randomization.

The study population was 83% male, 85% Caucasian, 51% men who have sex with men, 27% heterosexual, and 15% people who inject drugs. Participants had been on treatment with a fully suppressed viral load for a median of 100 weeks and the median current CD4 cell count was 589 cells/mm³ at the time of randomization.

After 48 weeks there was no significant difference in the proportion of participants in each study arm with undetectable viral load (<50 copies/mL), either in the entire study population or if those who stopped assigned treatment for reasons other than virological failure were excluded.

At 48 week 89% of those on the simplified regimen had viral load <50 copies/mL, compared to 93% in the triple-drug regimen group by intent-to-treat, missing-equals-failure analysis. More participants in the 2-drug arm had missing data at week 48 but fully suppressed viral load at their last clinic visit (5% vs 2%).

Single viral load blips were somewhat more frequent among those receiving a triple-drug regimen (13.2% vs 8.9%), but this difference was not statistically significant; 4.5% of those receiving the 2-drug regimen had 2 viral load blips compared to 2.6% of the triple-drug group.

Resistance testing of individuals who experienced virological rebound was possible in 5 cases where viral load rose above 400 copies/mL. Genotype testing failed in 2 of 5 cases. Resistance to darunavir was detectable in 1 participant who had been taking a triple-drug regimen but experienced virological rebound to 447,557 copies/mL.

There was no significant difference in serious adverse events between the dual and triple-drug study arms (4.8% vs 4.9%) or in study drug discontinuation due to adverse events (0.8% vs 1.6%). No significant improvement in kidney function was observed in those who switched to the simplified regimen, nor in total cholesterol/HDL cholesterol ratio.

Presenting the results, José Arribas of Hospital La Paz in Madrid said that results of 4 randomized trials of simplification of a boosted protease inhibitor and lamivudine presented a good opportunity for a meta-analysis to inform future treatment guidelines, although some might wish to see evidence of longer-term durability of 2-drug regimens.

11/7/16

Source

F Pulido, E Ribera, M Lagarde, J Arribas, et al. Non-inferiority of dual-therapy (DT) with darunavir/ritonavir (DRV/r) plus 3TC versus triple-therapy (TT) with DRV/r plus TDF/FTC or ABC/3TC for maintenance of viral suppression: 48-week results of the DUAL-GESIDA 8014 trial. HIV Drug Therapy 2016. Glasgow, October 23-26, 2016.AbstractO331.