Lower dose efavirenz (EFV), dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF) are expected to make up a large chunk of the adult first-line market over the next five years, and contribute to treatment cost reductions, according to recent projections by The Clinton Health Access Initiative (CHAI).
CHAI’s ARV Market Report – now in its 6th year – provides a global perspective on the antiretroviral (ARV) marketplace in low- and middle-income countries (LMICs) each year and describes CHAI’s expectations of the market’s evolution over the subsequent five years.
By the end of 2014, 13.5 million people were receiving ART in LMICs. ART coverage grew from 15% in 2009 to 40% in 2014 (including all HIV positive people at all CD4 counts) – coverage rates that year were 29% of children and 41% of adults. CHAI notes that the pace of scale up in 2014 (another 1.8 million additional people on ART since 2013) was similar to that seen in the previous year (2 million more people on ART from 2012 to 2013). By 2018 several countries are projected to approach universal coverage, including Rwanda, Uganda and Swaziland for adults, and Vietnam for children.
The report outlines imminent World Health Organisation (WHO) guideline changes that are likely to increase the overall ARV market size. Most importantly, the adoption of test and treat, so that all 36.9 million HIV positive people will be eligible for treatment, but also the recommendation of oral PrEP for people at risk of HIV, that once implemented, will lead to more demand for tenofovir disoproxil fumarate (TDF).
Brazil announced its adoption of test and treat in 2013 and saw a 27% increase in people receiving ART in 2014 (coverage went from 39% to 48% by the end of 2014). CHAI notes that Brazil’s domestic manufacturing capacity distinguishes it from other LMICs and might allow faster ART scale up than elsewhere. Other than Brazil, Malawi and Rwanda have announced plans to adopt test and treat – both countries already have relatively high coverage of more than 50%.
CHAI says that the immediate effect of the test and treat recommendation on ART scale up is unclear but as a “conservative” projection 23 million people are likely to be on ART in LMICs by 2019 (95% adults and 5% children).
The report shows how the price of recommended generic ARVs has stabilised and well-established drugs reached the minimum prices at which they can feasibly be produced. Pipeline products are expected to drive the next major drop in ART cost.
Generic accessible (GA) LMICs can look forward to several new drugs and formulations for adults, including DTG, EFV 400 mg and TAF, which are expected to significantly reduce the cost of first-line treatment.
Several generic companies have begun developing fixed dose combinations (FDC) of TDF/3TC/EFV 400 mg and these are expected to be available in mid- to late-2016.
Aurobindo has submitted a generic single DTG to the US FDA in May 2015, which is likely to be available in mid-2016. Generic DTG-based FDCs are likely to be available from 2017.
WHO has indicated that both EFV 400 mg and DTG will be recommended as part of alternative first-line regimens with some restrictions, until there is enough evidence to use them in all populations (notably in TB coinfected people and pregnant women).
CHAI predict that EFV 400 mg and DTG will have a substantial impact on the first-line market by 2019. By this time DTG is expected to gain 37% and EFV 400 mg 19% of the adult first-line NNRTI/INSTI market – respectively 7.2 million and 3.8 million people.
TDF made up 72% of the first-line NRTI market in GA LMICs in 2014 – 8.3 million people received this drug as part of adult first-line regimens by the end of that year.
The US FDA approved TAF as part of an FDC in November 2015, and news is expected about the dual co-formulation TAF/FTC in April 2016. A generic TAF-based FDC is expected mid-2018. With the caveat that various active product ingredient (API) production steps need to be optimised by generic manufacturers, CHAI note that TAF will cost a lot less than TDF as its dose is about 10-fold lower.
Uptake of TAF is likely to begin in the latter half of 2018. In the first year that it is available, TAF is likely to capture up to 22% of the first-line NRTI market in GA LMICs. Eventually TAF is projected to almost entirely replace TDF.