Background:  Stavudine (d4T) is included in first-line antiretroviral (ARV) regimens in most developing countries and is responsible for the majority of toxicities and drug switches. Many countries are considering replacing d4T with tenofovir (TDF), which is more expensive than d4T, but causes fewer adverse events. We estimated the increase in cost to South Africa’s government if it replaced d4T with TDF, given expected savings in the cost of managing toxicities.

Methods:  We modeled the ARV and toxicity management costs of treating a hypothetical cohort of 1000 patients with the current first-line regimen of d4T-lamivudine (3TC)-efavirenz (EFV) (d4T scenario) and compared them with the ARV and toxicity management costs of a regimen of TDF-3TC-EFV (TDF scenario). For the d4T scenario, data from a public hospital in Johannesburg were used to estimate rates of toxicities and resulting drug switches and resource utilization. Corresponding rates and resource use parameters for the TDF scenario were estimated from the literature. Toxicities attributed to d4T were peripheral neuropathy, hyperlactatemia/lactic acidosis, lipodistrophy, and pancreatitis. Renal failure was the only toxicity attributed to TDF. Resources used for toxicity management included inpatient admissions, outpatient visits, laboratory tests, and drugs. We used the current public sector price for d4T ($3.15/month) and the CHAI price for TDF ($12.42/month).

Results:  In the d4T scenario, 50.5% of the cohort experienced an actual or suspected d4T-related toxicity and 16.2% were switched to a new drug (primarily zidovudine [AZT]) by the end of 2 years. Hyperlactatemia and peripheral neuropathy accounted for 64% and 26% of all toxicities, respectively. In the TDF scenario, 2.5% of the cohort experienced a TDF-related toxicity and were switched to AZT. Average toxicity management costs ranged from $45 for mild hyperlactatemia to $5506 for lactic acidosis. After 24 months, the total cost of the TDF scenario exceeded the total cost of the d4T scenario by 15%. The average increase in cost per patient treated was $89/year. Savings on toxicity management offset 41% of the higher price of TDF. Switching to TDF in the first-line regimen would be cost-neutral at a price of $5.00/month.

Conclusions:  The reduction in toxicities expected from a switch from d4T to TDF would offset some but not all of the higher cost of TDF at current drug prices. If benefits to patients of lower toxicity rates, including a potential reduction in loss to follow-up and mortality, were included, TDF may be cost-effective even at its current price.