Cost-effectiveness of tenofovir instead of zidovudine for use in first-line antiretroviral therapy in settings without virological monitoring.
BACKGROUND
The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy.


METHODS
We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested.


RESULTS
In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%]) compared with first-line TDF users (31% [29%; 33%]). Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF) in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]). At the time of second-line initiation, a higher proportion (16%) of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively). In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY) was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315), which was below the WHO threshold for high cost effectiveness (US$ 2154).


CONCLUSIONS
Using TDF instead of ZDV in first-line treatment in resource-limited settings is very cost-effective and likely to better preserve future treatment options in absence of virological monitoring.
Research Department of Infection and Population Health, University College London, London, United Kingdom. viktor.vonwyl@css-institut.ch
Viktor
V
von Wyl
Valentina
V
Cambiano
Michael R
MR
Jordan
Silvia
S
Bertagnolio
Alec
A
Miners
Deenan
D
Pillay
Jens
J
Lundgren
Andrew N
AN
Phillips
D000225:Adenine / Q000031:analogs & derivatives* / Q000191:economics / Q000494:pharmacology; D000328:Adult; D017954:Africa South of the Sahara; D044966:Anti-Retroviral Agents / Q000191:economics* / Q000494:pharmacology; D003362:Cost-Benefit Analysis; D024882:Drug Resistance, Viral; D058872:Epidemics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000191:economics* / Q000494:pharmacology; D013269:Stochastic Processes; D000068698:Tenofovir; D016896:Treatment Outcome; D015215:Zidovudine / Q000191:economics* / Q000494:pharmacology
D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine