AIDS Drug Regimens That Are Worth Their Costs

The American public is justifiably celebrating the recent good news that opportunistic illnesses and deaths related to acquired immunodeficiency syndrome (AIDS) declined nationwide in 1996 for the first time since the pandemic began more than 15 years ago.¹ These trends reflect advances in opportunistic infection prophylaxis and highly active antiretroviral therapy and interventions to prevent transmission of human immunodeficiency virus (HIV) infection. Published guidelines have provided thoughtful distillations of complex research results for widespread clinical use.^{2 - 6} Despite this, some population groups have not benefited from the new therapies. In fact, increased incidences of AIDS-related opportunistic illnesses in 1996 were experienced by black and Hispanic men and women with heterosexual exposures.¹ The disparity in opportunistic infection trends between population groups most likely reflects differences in access to the full range of new therapies now available.⁷ Barriers to access are depriving many patients with HIV infection of life-extending health care.

If treatment of HIV and opportunistic infections can extend life, why are some patients still not benefiting from these therapies? Included among the reasons are that many HIV-infected persons are hesitant to be tested, are unable or unwilling to get timely and expert clinical care, or do not fully adhere to the difficult treatment regimens. The large and increasing costs of AIDS drugs also contribute to the access gap. Just 2 years ago, basic HIV therapy generally included zidovudine and trimethoprim-sulfamethoxazole as prophylaxis for Pneumocystis carinii pneumonia (PCP), at an annual cost of $3000.⁸ Today basic therapy involves 4 or 5 drugs, at an annual cost of more than $12000.^{3 ,5 - 6 ,8} Funding for AIDS Drug Assistance Programs (ADAPs), created to help uninsured and underinsured patients purchase medicine, has not kept up with the new demands. Many ADAPs have had to cap enrollment, restrict access to medications, or delay or suspend coverage of new therapies.⁹

To confront the issue of access to the expensive new AIDS therapies, we must be able to demonstrate that they are worth the cost. In this issue of THE JOURNAL, Freedberg and colleagues¹⁰ help place the cost of opportunistic infection prophylaxis in perspective. They performed a cost-effectiveness analysis of 6 antimicrobial agents alone and in combination and determined optimal strategies to maximize life expectancy and quality of life while minimizing cost. Their results confirm previous studies that found trimethoprim-sulfamethoxazole is highly cost-effective in preventing PCP and that oral ganciclovir is not cost-effective in preventing cytomegalovirus disease.^{11 - 12} Their more surprising finding is that Mycobacterium avium complex (MAC) prophylactic regimens, which cost up to $2900 each year,^{5 ,8} are reasonably cost-effective. However, their most important finding is that some combination regimens are reasonably cost-effective. Using the standard measurement of cost per quality-adjusted life year (QALY),¹³ Freedberg and colleagues determined that the combination of trimethoprim-sulfamethoxazole and azithromycin costs $29000 to extend life expectancy by 1 QALY.

Is $29000 per QALY a bargain or an extravagance? Most people may have a good sense of the worth of commonly purchased commodities, but few have a feel for what constitutes a reasonable cost for an intervention that extends life by 1 QALY. In a review of 310 medical interventions that save lives, Tengs and colleagues¹⁴ found that the median cost per life-year saved for preventing disease is $23000 and for preventing disability is $22000. Examples of widely accepted medical interventions include $15000 for hypertensive drug therapy, $22000 for breast cancer treatment, $26000 for coronary artery bypass graft surgery, $46000 for renal dialysis, and $154000 for hypercholesterolemia treatment.¹⁴ If these costs were adjusted for quality of life, they surely would be even higher. Nonetheless, these standard therapies are considered to be worth their costs.

Several of the prophylaxis regimens studied by Freedberg and colleagues¹⁰ fall into the cost range of these widely accepted therapies. Three of these strategies also were found to "dominate" the others. That is, they both extend life and save money relative to the competition.¹⁵ Trimethoprim-sulfamethoxazole alone is cost-effective in preventing both PCP and toxoplasmosis. Even more effective is the combination of trimethoprim-sulfamethoxazole with a macrolide to also prevent disseminated MAC disease. This combination is also recommended in the 1997 US Public Health Service–Infectious Diseases Society of America guidelines on preventing opportunistic infections.^{5 - 6} Freedberg and colleagues found that this combination plus fluconazole, added to prevent invasive fungal infections, is also reasonably cost-effective.¹⁰ Nevertheless, fluconazole as primary prophylaxis is not usually recommended because of concerns about toxicity, drug interactions, and the potential development of fungal resistance.^{5 - 6} In a sensitivity analysis, Freedberg and colleagues even factored in the costs and effects of triple antiretroviral therapy regimens containing a protease inhibitor. Although the data are too speculative to provide firm conclusions, the authors found that adding these very expensive drugs to prophylactic regimens also may result in cost-effectiveness ratios that are within the range of other widely accepted medical therapies.

For the first time in the history of the AIDS epidemic, HIV therapies are effective enough to reduce opportunistic infection and death rates on a nationwide scale. Although these new drug regimens may seem expensive, Freedberg and colleagues¹⁰ demonstrate that the costs of several regimens, relative to the benefit of extending quality life, fall within the widely accepted range of other medical care. The most highly recommended and effective regimens are worth their costs. Providing timely access to these cost-effective AIDS drugs to all patients with HIV infection can add quality years to their lives.