A farewell to didanosine: harm reduction and cost savings by eliminating use of didanosine.

Didanosine (ddI) is a nucleoside reverse transcriptase inhibitor associated with adverse events and public health concerns which have diminished its place in HIV clinical practice, particularly in resource-rich settings. While international guidelines do not contain ddI-containing regimens in preferred first- or second-line antiretroviral therapy (ART), there is no guidance for management of patients currently on ddI. In 2012 at least 20 countries purchased a total of $1-2 million of ddI. Drug purchase data in that year show 3.2-10.3 times higher costs for ddI compared to lamivudine (3TC). Given issues of multiple toxicities, monitoring, drug interactions, inconvenience, and virologic efficacy, as well as cost and formulary concerns, national (including resource-limited setting) ART programmes should consider complete phase-out of ddI.

Optimizing antiretroviral product selection: a sample approach to improving patient outcomes, saving money, and scaling-up health services in developing countries.

Over the last decade, increased funding to support HIV treatment programs has enabled millions of new patients in developing countries to access the medications they need. Today, although demand for antiretrovirals continues to grow, the financial crisis has severely constrained funding leaving countries with difficult choices on program prioritization. Product optimization is one solution countries can pursue to continue to improve patient care while also uncovering savings that can be used for further scale up or other health system needs. Program managers can make procurement decisions that actually reduce program costs by considering additional factors beyond World Health Organization guidelines when making procurement decisions. These include in-country product availability, convenience, price, and logistics such as supply chain implications and laboratory testing requirements. Three immediate product selection opportunities in the HIV space include using boosted atazanavir in place of lopinovir for second-line therapy, lamivudine instead of emtricitabine in both first-line and second-line therapy, and tenofovir + lamivudine over abacavir + didanosine in second-line therapy. If these 3 opportunities were broadly implemented in sub-Saharan Africa and India today, approximately $300 million of savings would be realized over the next 5 years, enabling hundreds of thousands of additional patients to be treated. Although the discussion herein is specific to antriretrovirals, the principles of product selection are generalizable to diseases with multiple treatment options and fungible commodity procurement. Identifying and implementing approaches to overcome health system inefficiencies will help sustain and may expand quality care in resource-limited settings.

Didanosine, lamivudine-emtricitabine and efavirenz as initial therapy in naive patients.

There are currently several suitable and different antiretroviral regimens to start highly active antiretroviral therapy (HAART), and many clinicians and patients prefer once-daily therapy. The efficacy and potency of efavirenz (EFV) has been established in many clinical trials and cohort studies; its pharmacokinetics, allowing for a convenient once-daily administration, make EFV one of the first agents to be included in once-daily regimens in naive patients. The two nucleoside reverse transcriptase inhibitors (NRTIs) accompanying the third drug have become the central skeleton, or the 'backbone' of the therapeutic scheme. Among the different NRTI pairs, a didanosine-lamivudine (3TC) or emtricitabine backbone for combination antiretroviral therapy may be a good option compared with any current NRTI-combinations due to its security, tolerance and once-daily dose. In this article, we review the advantages and drawbacks of didanosine-XTC-EFV as the initial regimen of HAART in HIV-infected patients.

Hydroxychloroquine, hydroxycarbamide, and didanosine as economic treatment for HIV-1.

Most people who have HIV-1 and live in less-developed countries cannot afford standard combination antiretroviral therapy, and more economical approaches to treatment are therefore needed. We treated 22 patients who were infected with HIV-1 (viral load < 100000 copies/mL and CD4 count >150 cells/microL) with hydroxychloroquine (200 mg), hydroxycarbamide (hydroxyurea) (500 mg), and didanosine (125-200 mg), taken twice daily. Treatment was well tolerated, with few serious adverse events. Viral load showed a sustained decrease of 1 3 log, and CD4 count was maintained (percentage increase; 2 9%) over 48 weeks in the 16 evaluable patients. This new combination of drugs could be suitable for countries that have restricted resources, but should first be further investigated.

[Cost effectiveness analysis of highly active antiretroviral therapy in HIV asymptomatic patients]. / Análisis coste-efectividad del tratamiento antirretroviral de gran actividad en pacientes infectados por el VIH asintomáticos.

BACKGROUND: Assessment of cost and effectiveness in highly active antiretroviral therapy (HAART) in HIV asymptomatic patients. PATIENTS AND METHODS: A cohort of several asymptomatic HIV-infected patients were observed under real practice and treated with two nucleosid analogues (AN) of which therapy was modified. A protease inhibitor (PI) was added and at least one AN was changed (or not), following the current clinical recommendations (1997). Data on direct cost (drug cost, visits and clinical procedures) were then recorded both three and six months after the beginning of the study. Data on effectiveness (percentage of patients with undetectable levels of viral load) and quality of life were next measured according to the EuroQol, and recorded at the same time. All patients used a monthly diary to keep record of resource consumption and quality of life progress. RESULTS: All treatment regimens were effective in lowering the viral load and improve quality of life. The less expensive HAART was AZT + 3TC + IND (1,037,757 pesetas) and AZT + ddl + IND (1,045,339 pesetas), but both were the least effective to reduce patient's viral load to undetectable levels (52.7 and 57.7% respectively); meanwhile d4T + 3TC + IND (1,188,177 pesetas) and d4T + ddl + IND (1,212,285 pesetas) were more expensive but more effective (67.9 and 66% respectively). Cost-effectiveness ratios ranged between 9,896 and 13,122 pesetas. There was no statistically significant differences in quality of life among the different HAART regimens. CONCLUSIONS: HAART implementation is effective in reducing patients' viral load to undetectable levels and to slightly improve their quality of life after six months. Costs and effectiveness vary according to the type of HAART treatment used.

Modeling the use of triple combination therapy in five countries: nevirapine, Zidovudine, and Didanosine.

OBJECTIVE: In this study, we modify previously published models to estimate the short- and long-term consequences of nevirapine triple combination therapy use in five developed countries. Current pharmacoeconomic practice requires the de novo model development for each new therapy comparison. This approach is lengthy and costly, and it may yield models with very different structures. Standardized, detailed disclosure of model assumptions and parameters makes it possible to recycle published models with minor structural modifications to examine the efficiency of therapies based on new trial data. METHODS: Two well-publicized models of HIV therapy are modified to fit new trial data comparing double and triple combination therapy with nevirapine; model parameters are adjusted to represent clinical practice and cost structure in five countries. A short-term model uses trial data from advanced-stage patients to estimate first-year costs and consequences. A long-term model uses data from antiretroviral-naïve patients to estimate long-term cost-effectiveness. RESULTS: During the first year, for each 100 individuals treated with nevirapine triple combination therapy, 2.7 deaths and 30.8-31.4 opportunistic disease events would be averted compared to employing dual therapy. Additionally, 61% to 142% of the first-year costs of nevirapine therapy would be offset by other medical care costs savings [FF19,749, DM3,778, 3334 (x1000) lire, 293 (x1000) ptas, and US $3,569]. Compared to dual combination therapy, nevirapine triple combination therapy is predicted to yield incremental cost-effectiveness ratios (discounted at 3%) of FF101,057, DM30,709, 28,066 (x1000) lire, 1294 (x1000) ptas, and US $14,338. CONCLUSION: Published, well-constructed, and documented cost-effectiveness models can be reused to estimate the economic impact of therapies for HIV disease. Such models can also be used to provide insight into the factors that affect efficiency across countries. Our use of clinical trial data on nevirapine, together with published HIV economic models, provides support for the hypothesis that nevirapine is cost-effective under the cost structures of five developed countries.

Changing cost of English HIV service provision 1996-1997. NPMS Steering Group. National Prospective Monitoring System.

The objectives of this study were to provide individual and population-based unit cost estimates of HIV treatment and care by stage of HIV infection for adults in England and estimate the financial impact of the use of combination antiretroviral therapy. Individual unit cost estimates were calculated, based on 1997 activity data, and linked to the number of diagnosed HIV-infected individuals using statutory medical services by clinical stage of HIV infection in England during 1997 to obtain population-based cost estimates; these were compared with 1996 estimates. Most clinical guidelines now recommend the use of 3 antiretroviral agents, but cost estimates for mono and dual therapy were included as baseline estimates. Baseline costs for treating AIDS patients with zidovudine (AZT) monotherapy were estimated at pound sterling 16,830 (95% CI 14,633-18,985) per patient-year which was substantially lower than the 1996 estimate; costs for asymptomatic individuals and people with symptomatic non-AIDS were pound sterling 4450 (95% CI 3521-5612) and pound sterling 7289 (95% CI 6169-8386) per respective patient-year which did not differ substantially from 1996. The total annual population cost estimate for HIV service provision amounted to pound sterling 128 million (95% CI pound sterling 109m to pound sterling 147m), if all patients with HIV disease were treated with AZT monotherapy only. For all eligible patients to be treated with 2 nucleoside reverse transcriptase inhibitors (NRTI) (AZT and didanosine (ddI) or zalcitabine (ddC)), cost estimates amounted to pound sterling 161m (95% CI pound sterling 141m to pound sterling 181m), while for triple therapy, annual estimated expenditure amounted to pound sterling 185m (95% CI pound sterling 165m to pound sterling 206m) when a non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine) was included or pound sterling 205m (95% CI pound sterling 186m to pound sterling 235m) when a protease inhibitor was included. Compared with 1996 population-based cost estimates, the estimates for monotherapy decreased by 14%, by 11% for dual therapy, by 10% for triple therapy which included a NNRTI and by 9% if a protease inhibitor was used as part of a triple therapy regimen. Similarly, compared with 1996 estimates, the proportion of total costs attributable to treating asymptomatic individuals increased by 5% and 2-3% for people with symptomatic non-AIDS, while the proportion attributable for treating people with AIDS decreased by 8-9%.