Two-drug ART with dolutegravir-lamivudine would be cost-effective and achieve substantial cash savings

Virologically suppressive first-line antiretroviral treatment with a two-drug regimen of dolutegravir (Tivicay) and lamivudine would be highly cost effective and could save US health systems approximately $500 million over five years, according to the results of a mathematical model published in the online edition of Clinical Infectious Diseases. Switching a quarter of currently suppressed patients to the two-drug combination could achieve five-year savings of $3 billion.

“We demonstrate that an induction-maintenance strategy of three-drug initial therapy with DTG/ABC/3TC [dolutegravir/abacavir/lamivudine] followed by DTG+3TC maintenance would be cost-effective in the US under plausible virologic efficacy assumptions; DTG+3TC as initial therapy could be even more cost effective,” comment the researchers. “We find that the induction-maintenance and two-drug strategies, if adopted, could save over $500 million or $800 million, respectively, in HIV therapy costs in the first five years compared to the current standard of care.”

The study’s findings are described as “important” by the authors of an accompanying editorial, who suggest that cost savings achieved with effective two-drug therapy could be used to improve rates of engagement and retention in care, both key to controlling the HIV epidemic in the US.

First-line HIV therapy normally consists of three drugs from two separate antiretroviral classes. This treatment usually costs upwards of $30,000 per patient, per year.

Results of a pilot study presented to the 15th European AIDS Conference this year showed that first-line treatment with two just two drugs – the potent integrase inhibitor dolutegravir with lamivudine – had excellent virological efficacy over 48 weeks, with a favourable safely/toxicity profile. Full results will be published in 2016.

Investigators wanted to see if this two-drug combination would be cost effective and estimate the potential savings that would be achieved if it were used in first-line treatment strategies.

They constructed a model involving four treatment strategies for treatment-naïve patients in the US.

• No treatment – for modelling comparison.
• Initial treatment with dolutegravir and lamivudine.
• Induction and maintenance therapy – an initial three-drug regimen of dolutegravir/abacavir/lamivudine, followed by maintenance therapy with dolutegravir-lamivudine for patients with virological suppression after 48 weeks of induction therapy.
• Standard of care - three-drug therapy with dolutegravir/abacavir/lamivudine.

The authors calculated the incremental cost-effectiveness ratios (ICERs) for each strategy compared to the next least expensive strategy. A strategy was regarded as cost-effective if its ICER was below the accepted threshold of $100,000 per quality-adjusted life year (QALY). A quality-adjusted life year in health economic terms is a year of perfect health and the ICER is the extra cost of buying a year of perfect health with a new intervention compared to the existing standard of care.

It was estimated that 93% of patients would have virological suppression after 48 weeks of three-drug treatment. The investigators adopted a cautious approach to the efficacy of two-drug therapy, assuming that 87% of patients would have a viral load below 50 copies/ml after starting treatment with this combination. They also assumed a virological failure rate of 0.6% per month for patients taking two-drug maintenance therapy; this compared to a monthly failure rate of just 0.1% for patients receiving the standard of care.

After applying discounts, the cost of annual treatment with dolutegravir/abacavir/lamivudine was input at $24,500, and annual treatment with dolutegravir-lamivudine was calculated as costing $15,200.

The five-year survival rate was 90% for standard of care, induction and maintenance therapy and two-drug treatment. The proportion of patients remaining on first-line treatment at year five ranged from 97% for patients receiving standard of care to 89% for patients who received initial two-drug therapy.

Compared to no treatment, the ICER for induction and maintenance therapy was $22,500/QALY. Compared to induction and maintenance therapy, the ICER for standard of care was over $500,000/QALY and was not cost effective. The clinical and economic outcomes of two-drug treatment were almost identical to those for induction and maintenance therapy (ICER compared to no therapy, $26,000/QALY).

A 50% uptake by patients starting ART of either induction-maintenance therapy or two-drug therapy was calculated to achieve five-year cost savings of $550 million and $800 million, respectively. Savings reached $3 billion if 25% of currently suppressed patients switched to dolutegravir-lamivudine.

“Given this substantial potential economic benefit alongside excellent clinical outcomes, if upcoming pilot data are promising, a fully-powered clinical trial to evaluate the non-inferiority of these strategies should be conducted,” conclude the investigators.

The study’s findings are described as “novel and compelling” in the accompanying editorial, the authors commenting, “two-drug strategies offer real potential to reduce HIV treatment costs, not only in the United States but in other countries as well.”

Girouard MP et al. The cost-effectiveness and budget impact of two-drug dolutegravir-lamivudine regimens for the treatment of HIV infection in the United States. Clin Infect Dis, online edition, 2015.

Koenig SP et al. Stemming the tide: can new approaches to HIV treatment reverse the trend of rising drug prices in the United States? Clin Infect Dis, online edition, 2015.