Two research teams have reached similar conclusions about the cost-effectiveness of various first-line ART regimens in resource-limited settings. Less toxic drugs may prove cost-effective for many low- and middle-income countries as they consider how to phase out the cheapest and most toxic regimen based on stavudine (d4T), the Eighteenth International AIDS Conference heard on Monday July 19th.
Newly published guidance from the World Health Organization (WHO) recommends that stavudine (d4T) should be phased out wherever possible due to the high rate of possibly irreversible toxicities associated with the drug, such as peripheral neuropathy (nerve damage in the feet and limbs) and lipoatrophy (fat loss in the limbs and face), and the life-threatening toxicity lactic acidosis.
However, countries face a dilemma because d4T-based treatment is markedly cheaper than regimens based on zidovudine (AZT) or tenofovir.
As earlier treatment is now recommended, particularly for pregnant women and people with TB, there is also a need to look for regimens that do not contain nevirapine (NVP), due to the higher risk of liver toxicity in women with CD4 counts above 250 and because of the potential for a negative interaction between nevirapine and the TB drug rifampicin.
Severe toxicity requires switches to more expensive drugs, and may also lead to treatment failure if patients stop taking their drugs due to unacceptable side-effects. There is also some evidence that tenofovir-based regimens are more likely to control HIV in the long term, reducing the risk of virological failure of treatment and the subsequent need to switch to a second-line regimen that may cost up to three times more than first-line treatment.
For all these reasons, WHO now recommends that the preferred regimen is a fixed-dose combination of tenofovir, efavirenz and either 3TC or FTC. This regimen remains substantially more expensive than d4T-based ART, and is likely to remain so due to more complex manufacturing processes.
The Clinton HIV/AIDS Initiative projects that if orders for the combination increase, it will be possible to drive down the price from around US$210 in 2010 to $160 by 2012, but it will be difficult to achieve further reductions after that point.
In comparison, d4T-based treatment costs as little as $84 a year, while AZT-based treatment costs around US$120 to 140 a year.
In order to assess the likely resource needs as a result of the new guidelines, UNAIDS conducted a cost-effectiveness analysis of various ART regimens, using data from Africa in order to look at the relative costs of various regimens.
UNAIDS modeled the cost-effectiveness of various regimens in a cohort of 10,000 notional patients over ten years, using data from existing African cohorts to inform estimates of effectiveness and retention, with conservative assumptions about survival after starting ART ((5.3 to 8.7 years).
The UNAIDS researchers noted that the discounted cost per quality-adjusted life year gained (QALY) for all three of their regimens – US$618 for d4T/3TC/NVP, US$641 for AZT/3TC/NVP and US$727 for TDF/3TC/NVP – were well below sub-Saharan Africa’s US$1695 GDP per capita, and therefore very affordable under WHO criteria for cost-effectiveness.
They highlighted the cost-effectiveness of nevirapine/zidovudine/lamivudine (NVP/AZT/3TC) and nevirapine/tenofovir/lamivudine (NVP/TDF/3TC) compared to nevirapine/stavudine/lamivudine (NVP/d4T/3TC). The two superior regimens had incremental cost-effectiveness ratios of US$1170 and US$1520, respectively. (The incremental cost-effectiveness ratio indicates the additional amount of money needed to buy the same outcome in terms of quality-adjusted years of life.)
They also observed that even small reductions in the prices of some drugs would facilitate the use of more effective ART regimens.
Another group of researchers from Stanford University, assessing treatment in South Africa, performed cost-effectiveness analyses of those three regimens along with efavirenz/zidovudine/lamivudine (EFV/AZT/3TC) and efavirenz/tenofovir/lamivudine (EFV/TDF/3TC).
They concluded that NVP/d4T/3TC, the most commonly dispensed regimen in South Africa, is distinctly inferior to NVP/AZT/3TC from a cost-effectiveness standpoint.
In the South African study, NVP/TDF/3TC was associated with considerably better health outcomes at a cost of US$1045 per quality-adjusted life year (QALY) gained in relation to NVP/AZT/3TC.
The South African study indicated that EFV/TDF/3TC, which was associated with the best survival, fewest opportunistic diseases and least regimen-switching, had an incremental cost-effectiveness ratio of US$5950 per QALY gained in comparison to NVP/TDF/3TC. Lowering the cost of EFV to $67 annually, the researchers suggested, would make EFV/TDF/3TC a cost-saving option.
Grujovic A et al. Cost-effectiveness analysis of first-line ART regimens for the treatment of HIV-infected patients in resource-limited settings. 18th International AIDS Conference, Vienna, abstract MOAE0404, 2010.
Eran Bendavid's presentation and abstract are available on the official conference website.
Bendavid et al. Cost-effectiveness of World Health Organization first-line HIV treatment guidelines in Africa. 18th International AIDS Conference, Vienna, abstract MOAE0403, 2010.