Model predicts benefit of dolutegravir for all in sub-Saharan Africa outweighs risk

21 January 2019. Related: Treatment access.

Polly Clayden, HIV i-Base

A policy where a regimen tenofovir, lamivudine, and dolutegravir is given to all adults on ART, regardless of viral load suppression and intention to have children, provided better health outcomes than policies restricting its use.

These findings, from a modelling study, authored by Andrew Phillips from University College London and colleagues were published online 29 November in the Lancet HIV.

The study used an existing individual-based model of HIV transmission progression and the effect of ART. The model is based on sub-Saharan Africa. The aim was to help inform policy makers on approaches to dolutegravir (DTG) provision that are likely to lead to the greatest health gains at a population level.

For each scenario, the authors considered the situation in 2018 and compared outcomes with potential ART regimen policies over a 20-year time frame.

The different regimen policies included in the model were:

Tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV) for all
TDF, 3TC and DTG dependent on viral suppression and intention to have (more) children
TDF, 3TC and DTG dependent on intention to have children
TDF, 3TC and DTG dependent on viral suppression only

TDF, 3TC and DTG for all

The authors assumed a rate of reaching a point of intention to have no more children to be 0.005 per 3 months from 25 years. This resulted in 16% of women aged 15–55 years not intending to have children.

They also assumed that women who do not intend to have more children are able to access contraception and its efficacy is 80% (50% in sensitivity analysis).

For acquisition of resistance they assumed a 13 times lower rate of resistance to DTG than to EFV.

They assumed double the risk of neurological toxicity with EFV versus DTG and 1.5 higher potency for DTG versus EFV.

Excess risk of neural tube defects in infants born to women receiving DTG was assumed to be 0.58% (4/596, 0.67% minus 0.09% background rate in HIV negative women).

They also considered different rates of viral load implementation and regimen switch after viral load failure.

Health outcomes were measured in disability adjusted life-years (DALYs). Although these were modelled in adults only, the authors considered DALY effects of neural tube defects and vertical transmission of HIV.

The model revealed, a mean of 98% of people receiving ART over 20 years would be expected to receive DTG with a policy of TDF, 3TC and DTG for all, versus 43% if people with viral load greater than 1000 copies/mL on previous first-line and women who intended to have children were not included in the policy. With policies dependent on intention to have more children and viral suppression only, the respective proportions receiving DTG would be 54% and 85%.

With TDF, 3TC and DTG for all, DTG-related neural tube defects would occur in 0.6%, compared to 0.2%, 0.3% and 0.52% where policies depend on viral suppression and intention to have children, intention to have children only, and viral suppression only, respectively. But vertical transmission risk would be lower with TDF, 3TC and DTG for all, occurring in 2.8%, compared to 3.9%, 3.8%, 2.9% with the respective restrictions.

Providing TDF, 3TC and DTG for all was predicted to lead to more DTG resistance compared with restriction dependent on viral load suppression: 6.7% vs 4.4%. By the end of the 20-year time frame these proportions were: 9.4% vs 7.6%.

The number of deaths due to AIDS among people receiving ART declined with increased use of TDF, 3TC and DTG. Use of TDF, 3TC and DTG for all was predicted to lead to the most DALYs averted, 58,200 vs 22,300 for a scenario with DTG restriction dependent on viral suppression and intention to have more children.

Providing TDF, 3TC and DTG for all was also the most cost effective and would be cost saving over a 20 year horizon.

The authors concluded that using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to TDF, 3TC, and DTG for all substantially outweighed the risks.

Polly Clayden is also a co-author on this paper.

comment

These modelled projections are updated as more data from sub-Saharan Africa becomes available – for example this includes information from the NAMSAL study, conducted in Cameroon.

More data from trials conducted in the region, as well as more on the risk of neural tube defects will become available this year.

Reference

Phillips AN et al. Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study. Published online 29 November 29, 2018.
https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(18)30317-5/fulltext