South African women exposed to single-dose nevirapine (Viramune) are likely to gain the most benefit from antiretroviral therapy based on ritonavir-boosted lopinavir (Kaletra) followed by a nevirapine-based combination. This is also a ‘very cost-effective’ strategy, according to the results of a study presented in the 15th June edition of Clinical Infectious Diseases.
More than 100,000 women in South Africa have taken a single dose of nevirapine during childbirth to prevent transmission of HIV to their babies. A risk of this strategy is the development of nevirapine resistance in the mother, potentially limiting her future treatment options.
To predict the efficacy and cost-effectiveness of treatment in women previously exposed to nevirapine, a team of doctors developed a mathematical model. By using data from observational studies, clinical trials and costs of medicines, laboratory analysis and clinic visits in South Africa, the doctors estimated the life expectancy of women exposed to different treatment regimens, and their relative costs.
They calculated that the life expectancy was 43.7 months from the time the model was started in women who only received co-trimoxazole (Septrin) to prevent opportunistic infections. At the start of the study, the median age of the women entering the prediction model was 25 years, with a median CD4 cell count of 200 cells/mm3.
When they predicted the effect of a combination of nevirapine, d4T (stavudine, Zerit) and 3TC (lamivudine, Epivir), the doctors found that life expectancy increased to 77.4 months. Nevirapine resistance, which was present in 39% of the women in the simulation, shortened the estimated survival time by 11.6 months.
Women receiving the alternative regimen of Kaletra, AZT (zidovudine, Retrovir) and ddI (didanosine, Videx / VidexEC) had a life expectancy of 84.5 months.
However, this combination was more expensive than the nevirapine-based regimen, with an estimated total lifetime cost of $7700. This was equivalent to a cost-effectiveness of $4400 per year of life saved, when compared to no antiretroviral treatment.
The nevirapine regimen had a lifetime cost of $5310, which was equivalent to $800 per year of life saved.
The doctors also predicted the effects of starting treatment with one of these two regimens before switching to the other after treatment failure had occurred. They found that starting with the nevirapine-based regimen produced a life expectancy of 104 months at a lifetime cost of $8580. This was equivalent to a cost effectiveness of $1400 per year of life saved when compared to the nevirapine combination alone.
In contrast, starting with the Kaletra-based regimen led to a longer life-expectancy of 105 months, which would cost $8900 over a patient’s lifetime. Using Kaletra first had a cost-effectiveness of $2300 per year of life saved, when compared to the nevirapine-first strategy.
“Both strategies including two lines of antiretroviral therapy and the strategy including a single line of nevirapine-based antiretroviral therapy had incremental cost-effectiveness ratios less than the per capita gross domestic product of South Africa ($3290) and would be considered to be ‘very cost-effective’ by the Commission on Macroeconomics in Health,” the doctors conclude.
“The sequential regimen of a Kaletra-based antiretroviral treatment regimen followed by treatment with a nevirapine-based, second-line antiretroviral treatment regimen appears to be the optimal antiretroviral treatment strategy for the clinical management of South African women in need of antiretroviral treatment,” they add.
The investigators altered some of the parameters in their calculations, to determine how robust their predictions were. They found that life expectancy was closely linked to the prevalence of nevirapine resistance and to the effectiveness of nevirapine-containing treatment in women with nevirapine resistance. Starting treatment more than six months after single-dose treatment also increased the life expectancy of patients and the cost-effectiveness of the Kaletra-first strategy.
Decreasing the efficacy of second-line regimens by 10 to 20% resulted in women taking the nevirapine-first strategy having a longer life expectancy than the Kaletra-first strategy.
However, the doctors calculated that the cost of Kaletra would have to be reduced by 80% to make the Kaletra-first strategy more cost-effective than the nevirapine-first strategy.
“Reductions in the cost of Kaletra-based antiretroviral therapy, in particular, would further reduce the overall costs of care per individual, which may be required to allow for the fullest dissemination of antiretroviral therapy in South Africa and other resource-limited areas,” the doctors conclude.
A clinical trial called the Optimal Combination Therapy After Nevirapine Exposure (OCTANE) study is currently underway in Africa. This randomised study is comparing the responses of women exposed to single-dose nevirapine to antiretroviral treatment combinations, at least in the short-term. Until the results of this and similar trials are available, the results of simulations provide the best evidence for suitable treatment strategies in these women.
Holmes CB et al. Optimizing treatment for HIV-infected South African women exposed to single-dose nevirapine: balancing efficacy and cost. Clin Infect Dis 42: 1772-1780, 2006.