Laboratory monitoring of ART could be cost-effective for many countries

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Laboratory monitoring to determine when to switch to second-line treatment may be cost-effective for many countries and could substantially improve life expectancy, April Kimmel and colleagues reported in a modelling study using 1999 to 2008 data from the Ivory Coast (Côte d’Ivoire) published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Using laboratory monitoring to guide when to switch to second-line antiretroviral treatment improved survival; viral load and CD4 cell count monitoring increased life expectancy by 61% and 46%, respectively compared to first-line therapy only

The cost-effectiveness of laboratory monitoring is particularly dependent on the costs of second-line therapy, how resistance affects the benefits of second-line ART as well as the length of time on second-line ART after failure on first-line, the authors noted. Identifying treatment failure earlier will lead to switches to more costly drugs, but might reduce the transmission of drug-resistant virus.

Glossary

second-line treatment

The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs.

cost-effective

Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

first-line therapy

The regimen used when starting treatment for the first time.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

natural history

The natural development of a disease or condition over time, in the absence of treatment.

Immunological and virological monitoring is standard clinical practice in resource-rich settings. In resource-poor settings the role of monitoring in the management of antiretroviral treatment remains a subject of debate.

Effective budget planning requires an understanding of the clinical and economic benefits of laboratory monitoring for HIV management in resource-poor settings to assure the best available treatment options with limited resources.

The authors looked at the clinical benefits, cost and cost-effectiveness of CD4 count and/or viral load monitoring to guide switching to second-line treatment in West Africa’s Ivory Coast, a low-income country with an HIV prevalence of 3.9%.

Using a simulation model (the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Model) of the natural history and treatment of HIV disease, the authors analysed data from trials and studies, and used fee scales and cost databases to project life expectancy and the costs of the different strategies in switching.

Estimated direct medical costs for HIV-related care included inpatient care, outpatient visits, treatment of acute clinical events, other routine care, medications and laboratory costs.

Average first-line ART costs estimated at $121 were based upon a Médecins sans Frontières pricing guide and the different regimens used in a cohort of 10,000 (53% of whom were taking stavudine, lamivudine and nevirapine at a cost of $100 per year; 22% stavudine, lamivudine and efavirenz at a cost of $120 annually; 20% zidovudine, lamivudine and efavirenz at a cost of $177 annually; and 6% taking other regimens at a cost of $120 per year).

Second-line ART costs assumed the use of tenofovir/emtricitabine ($199 annually) plus lopinavir/ritonavir ($550) for a total of $749 each year. All costs were adjusted to 2006 price levels.

Outcomes were then compared using the incremental cost-effectiveness (ICER) ratio. Each outcome was expressed in 2006 United States dollars for each year of life gained (YLS). That is the additional costs of each strategy divided by its additional clinical benefit compared to the next less expensive strategy. Patient time and transportation costs were not included.

Earlier detection through CD4 cell count monitoring or viral load monitoring of first line ART failure meant higher CD4 cell counts when failure was detected, at a mean of 189 cells/mm³ and 467 cells/mm³, respectively. Thus a shorter time was spent on a failed regimen with earlier switching to second-line.

When compared to first-line ART only, a switch to second-line treatment resulted in varying increases in life expectancy according to the monitoring method used to determine when to switch.The greatest gain in life expectancy was seen iwhen virological testing was used to determine the switching time, (61% gain in life expectancy compared to 46% gain with CD4 monitoring and 24% with clinical monitoring.)

When compared to first-line treatment the incremental cost-effective ratio of switching for clinical monitoring and twice yearly CD4 cell count monitoring was $1679 and $2120 per year of life gained, respectively. The cost-effective ratio of twice yearly viral load testing ranged from $2920 at $87 for each test to $1990 at $25 per test for each year of life gained.

According to criteria developed by the WHO Commission on Macroeconomics and Health, interventions can be judged very cost-effective for a national health system if the incremental cost-effectivness ratio is no greater than a country’s GDP per capita, and cost-effective if the ICER is no more than three times a country’s per capita GDP.

The authors suggest a reduction in second-line costs and less time spent on second-line ART after failure will support the cost-effectiveness of viral load monitoring.

The authors note that in a clinic of 10,000 patients with a similar profile to that used in their analysis 66% of patients with CD4 guided switching would be alive at 10 years compared to 60% without. The resulting increase from $5040 to $6120 in total care costs for each person is a direct consequence of earlier switching to the more expensive second-line treatment.

The authors note that their findings are in line with other studies that have also tried to address the debate on laboratory monitoring to guide HIV treatment management in resource-poor settings.

Differences, they stress, include a focus only on switching as well as a healthier cohort. So the benefits from earlier switching guided by monitoring are greater and lead to lower cost-effective ratios for all monitoring tests.

Limitations, note the authors, include an assumption that monitoring tests provided a true reading of the underlying disease status and that laboratories used provide accurate and consistent results.

The different monitoring test technologies were not assessed. The authors note that while information on specific drug and/or regimen mutations exists, there is little on regimen-specific mutations on subsequent ART. So they suggest the method chosen to describe resistance “as a function of time on virologically failed ART most accurately reflects the evidence-base.”

They did not take into account that a decline in CD4 count might not correspond to virological failure and would mean that some are switched unnecessarily. This, they argue, further supports viral load monitoring.

They also did not include in their analysis the potential population-level benefits of decreased HIV transmission of resistant virus because of earlier switching. Again, if included, they suggest this would favour viral load monitoring.

And, in conclusion the authors note their findings “support the value of investing in low-cost viral load tests, reducing prices for second-line ART, and developing a better understanding of the relationships among delayed switching, development of resistance mutations, and subsequent antiretroviral efficacy.”

References

Kimmel AD et al. Laboratory monitoring to guide switching antiretroviral therapy in resource-limited settings: clinical benefits and cost-effectiveness. J Acquir Immune Defic Syndr, advance online publication. May 2010.