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IDWeek 2013: Long-acting Antiretrovirals May Improve Survival for HIV+ People with Poor Adherence

Published on Thursday, 03 October 2013 00:00

Written by Liz Highleyman

Long-acting antiretroviral formulations taken once-monthly or less have the potential to improve survival and quality of life for people with HIV, especially those who have difficulty achieving good adherence, but cost may be a barrier, according to a presentation at the Second IDWeek conference taking place this week in San Francisco.

Long-acting antiretroviral therapy (ART) administered as monthly or quarterly injections may be a more convenient way for some people to receive treatment, which could lead to improved adherence and in turn better viral suppression.

Two such formulations, a long-acting version of rilpivirine known as TMC278-LA and the experimental HIV integrase inhibitor GSK1265744, have showing promising pharmacokinetics, safety, and antiviral activity in early studies.

Eric Ross from Massachusetts General Hospital in Bostonand colleagues used mathematical modeling to predict the impact of long-acting ART on survival and cost-effectiveness for treatment-naive individuals under 4 scenarios:

Current standard of care using daily oral antiretrovirals, starting with a NNRTI-based regimen, moving on to protease inhibitors, and finally to integrase inhibitors and salvage regimens;

  • Late long-acting ART starting after multiple treatment failures;
  • Second-line long-acting ART start after first-line NNRTI failure;
  • First-line long-acting ART used as an initial regimen.

The model assumed a hypothetical cohort of previously untreated people with HIV based on demographic, CD4 T-cell count, and adherence data from published studies. Most (84%) were men, the mean age was 43 years, the baseline CD4 count was 320 cells/mm3, and they maintained 89% adherence on average. The analysis assumed that viral suppression rose linearly with increasing adherence when using daily ART group, but that both adherence and suppression remained consistently high when using long-acting injections.

The researchers projected changes in CD4 count, viral load, and retention in care over a lifetime. They looked at life expectancy, quality-adjusted life years (QALYs), and cost estimates based on 2012 U.S. price data:

  • Average first-line regimen: $24,000/year;
  • Boosted protease inhibitor regimen: $28,000/year;
  • Integrase inhibitor regimen: $39,000/year;
  • Integrase inhibitor salvage regimen: $40,000/year;
  • Long-acting ART regimen: $53,000/year

Importantly, they estimated that long-acting ART would cost 85% more than boosted protease inhibitor regimens, based on historical informationabout relative costs of novel long-acting formulations of drugs for other diseases.

Cost-effectiveness was determined by calculating whether the incremental cost per QALY gained was above or below $100,000, a commonly used threshold in the U.S.


  • Compared with a life expectancy of 23 years after ART initiation for people on daily therapy, the model predicted that those using long-acting formulations would increase their survival by several months:

o   23.5 years with late long-acting ART;

o   23.6 with second-line ling-acting ART;

o   23.7 with first-line long-acting ART.

  • Lifetime costs for long-acting ART under the late, second-line, and first-line scenarios were $420,000, $490,000, and $670,000, respectively, compared with USD$400,000 for current daily regimens.
  • Late long-acting ART after multiple treatment failures was cost-effective, coming in under the threshold at $90,000 per QALY.
  • Second-line long-acting ART was 10-fold more expensive, at %980,000 per QALY.
  • Starting long-acting ART as first-line therapy cost a whopping $6,190,000 per QALY.
  • However, the cost picture improved when the model took adherence into account.
  • Among individuals with very high adherence to daily regimens (as seen in some clinical trial populations), long-acting ART did not significantly improve survival, so it was not cost-effective under any scenario.
  • People with poor adherence to daily therapy, however, could see enough improvement in life expectancy that long-acting ART became feasible.
  • The researchers calculated that the cost of long-actingART would have to drop into the $27,000 to $34,000 per year range to become cost-effective for second-line therapy — close to the current price of boosted protease inhibitor regimens.

“Long-acting ART has the potential to improve survival of HIV patients, especially those with barriers to adherence,” the investigators concluded. “With a high cost, long-acting ART will be a good value when used selectively in poorly-adherent patients with multiple failures. With a cost near that of currently available regimens, long-acting ART could be cost-effective as second-line therapy.

The researchers stressed that because survival benefits of long-acting ART could be negligible for highly adherent patient groups, studies of this strategy “may underestimate its value” if they do not include individuals with barriers to adherence.

They also noted that this model did not incorporate the potential effect of long-acting ART on reducing the risk of HIV transmission, which would likely improve its value. Some experts have suggested that long-acting antiretrovirals may be ideal for pre-exposure prophylaxis, or PrEP, which depends on excellent adherence.

The historical 85% cost increase for novel long-acting drug formulations is perhaps the most flexible factor in this model. If advocates succeed in demanding lower prices, or if national health programs or private insurers refuse to pay such a high premium, long-acting ART could become cost-effective for more people.



E Ross, M Weinstein, B Schackman, et al. The clinical role and cost-effectiveness of long-acting antiretroviral formulations. 2nd ID Week Conference (IDWeek 2013). San Francisco. October 2-6, 2013. Abstract 78.