If people with viral loads above 1000 copies/ml on an existing first-line regimen and women intending to have children were excluded from dolutegravir treatment, only 43% of adults living with HIV would receive dolutegravir over a 20-year period. If only women intending to have children were excluded from dolutegravir treatment, 54% would receive the drug.
Over 20 years, the most restrictive dolutegravir prescribing guidelines would result in 4% fewer people having a viral load below 1000 copies/ml than with a universal dolutegravir policy, but the death rate in people on ART would be almost twice as high (1.25 deaths per 100 person-years vs 0.72 per 100 person-years).
Looking at adverse birth outcomes, the modelling found that neural tube defects would occur in 0.6% of births under a policy of universal dolutegravir prescribing, compared to 0.03% of births if women intending to have children were excluded from receiving dolutegravir. But because of the greater potency of dolutegravir and better viral suppression, the rate of mother-to-child transmission would be lower under a universal dolutegravir policy than if all restrictions applied (2.8% versus 3.9%).
Looking at the development of dolutegravir resistance – the rationale for the policy of restricting first-line switches to those with a viral load below 1000 copies/ml – the modelling showed that 6.7% of people over a 20-year period would have dolutegravir resistance (transmitted or acquired) under a universal policy. In comparison, 4.4% would have resistance under the policy of restricting first-line switches.
The universal dolutegravir regimen averted the largest number of disability-adjusted life years (DALYs) per year (58,200), compared to 22,300 for the most restrictive policy. DALYs measure the amount of life lost in a population as a result of premature death or disability.
For a country of 10 million people, all the dolutegravir regimens would save between $ 5 million and $ 10 million a year, with the greatest saving associated with the universal dolutegravir regimen.
The universal dolutegravir policy showed an incremental cost-effectiveness ratio of $ 44 compared to tenofovir, lamivudine and dolutegravir when restricted to people with viral load below 1000 copies/ml. All other policies showed fewer DALYs averted and higher cost and were therefore dominated.
The researchers say that the findings can be used to inform the development of national policies on dolutegravir use and that the views of people living with HIV on the risks and benefits identified in this analysis should also be sought as part of the national policy development process.