Cost-effectiveness of post-exposure prophylaxis following sexual exposure to HIV

OBJECTIVES: To assess the cost-effectiveness, relative to other health-related interventions in the U.S., of post-exposure prophylaxis (PEP) following potential HIV exposure through sexual contact with a partner who may or may not be infected, and to compare the relative cost-effectiveness of dual- and triple-combination PEP. METHODS: Standard techniques of cost-utility analysis were used to assess the cost-effectiveness of PEP with a four-week regimen of zidovudine and lamivudine, or zidovudine, lamivudine, and indinavir. Due to a lack of empirical data on the effectiveness of PEP with combination drug regimens, the analysis assumed that combination PEP was no more effective than PEP with zidovudine alone. The main outcome variable is the cost per quality-adjusted life year (QALY) saved by the program. RESULTS: Providing PEP to a cohort of 10,000 patients who report receptive anal intercourse with a partner of unknown HIV status (who is assumed to be infected with probability equal to 0.18) would prevent about 20 infections, at an average net cost of about US$ 70,000 per infection averted. The cost-utility ratio, US$ 6316 per QALY saved, indicates that PEP is highly cost-effective in this instance. Moreover, triple-combination PEP would need to be about 9% more effective than dual-combination PEP for the addition of indinavir to the regimen to be considered cost-effective. Prophylaxis following receptive vaginal exposure is cost-effective only when it is nearly certain that the partner is infected; PEP for insertive anal and vaginal intercourse does not appear to be cost-effective. CONCLUSIONS: From a purely economic standpoint, PEP should be restricted to partners of infected persons (e.g., serodiscordant couples), to patients reporting unprotected receptive anal intercourse (including condom breakage), and possibly to cases where there is a substantial likelihood that the partner is infected. Providing PEP to all who request it does not appear to be an economically efficient use of limited HIV prevention and treatment resources.     

Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. The Osservatorio SIFO sui Farmaci

OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost-effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost-utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost-effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93,000 (discounted) per individual, the absolute ratio of cost-effectiveness for zidovudine monotherapy was $36,980 per life-year, while the absolute cost-utility ratio was $47,112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an "average" cost-effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost-effectiveness and cost-utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.     

Occupational exposure to HIV: experience at a tertiary care center

We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers.     

Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention

OBJECTIVE: To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. METHOD: The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. RESULTS: Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. CONCLUSION: Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.     

Antiretroviral drugs as a public health intervention for pregnant HIV-infected women in rural South Africa: an issue of cost-effectiveness and capacity

OBJECTIVE: To estimate cost-effectiveness and capacity requirements for providing antiretroviral drugs to pregnant HIV-infected women in rural South Africa. SETTING: Hlabisa health district, where HIV prevalence among pregnant women was 26.0% in 1997. METHODS: Calculation of the number of paediatric HIV infections averted under three scenarios, and their cost. No intervention was compared with scenario A (zidovudine delivered within current infrastructure), scenario B (zidovudine delivered through enhanced infrastructure), and scenario C (short-course zidovudine plus lamivudine delivered through enhanced infrastructure). Cost-effectiveness was defined as cost per infection averted and cost per potential life-year gained. Capacity was determined in terms of staff and infrastructure required to effectively implement the scenarios. RESULTS: With no intervention, 657 paediatric HIV infections were projected for 1997. In scenario A this could be reduced by 15% at a cost of US$ 574 825, in scenario B by 42% at US$ 1520770, and in scenario C by 47% at US$ 764901. In scenario C, drugs accounted for 76% of costs, whereas additional staff accounted for 18%. Cost per infection averted was US$ 2492 and cost per potential life-year gained (discounted at 3%) was US$ 88. Cost of scenario C was equivalent to 14% of the 1997 district health budget. At least 12 extra counsellors and nurses and one laboratory technician, together with substantial logistical and managerial support, would be needed to deliver an effective intervention. CONCLUSION: Although antiretrovirals may be relatively cost-effective in this setting, the budget required is currently unaffordable. Developing the capacity required to deliver the intervention would pose both a major challenge, and an opportunity, to improve health services.     

Cost-effectiveness of HIV-prevention skills training for men who have sex with men

OBJECTIVE: A previous study empirically compared the effects of two HIV-prevention interventions for men who have sex with men: (i) a safer sex lecture, and (ii) the same lecture coupled with a 1.5 h skills-training group session. The skills-training intervention led to a significant increase in condom use at 12-month follow-up, compared with the lecture-only condition. The current study retrospectively assesses the incremental cost-effectiveness of skills training to determine whether it is worth the extra cost to add this component to an HIV-prevention intervention that would otherwise consist of a safer sex lecture only. DESIGN: Standard techniques of incremental cost-utility analysis were employed. METHODS: A societal perspective and a 5% discount rate were used. Cost categories assessed included: staff salary, fringe benefits, quality assurance, session materials, client transportation, client time valuation, and costs shared with other programs. A Bernoulli-process model of HIV transmission was used to estimate the number of HIV infections averted by the skills-training intervention component. For each infection averted, the discounted medical costs and quality-adjusted life years (QALY) saved were estimated. One- and multi-way sensitivity analyses were performed to assess the robustness of base-case results to changes in modeling assumptions. RESULTS: Under base-case assumptions, the incremental cost of the skills training was less than $13,000 (or about $40 per person). The discounted medical costs averted by incrementally preventing HIV infections were over $170,000; more than 21 discounted QALY were saved. The cost per QALY saved was negative, indicating cost-savings. These results are robust to changes in most modeling assumptions. However, the model is moderately sensitive to changes in the per-contact risk of HIV transmission. CONCLUSIONS: Under most reasonable assumptions, the incremental costs of the skills training were outweighed by the medical costs saved. Thus, not only is skills training effective in reducing risky behavior, it is also cost-saving.     

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team

BACKGROUND: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. METHODS: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. CONCLUSIONS: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.     

Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus

BACKGROUND: The Pediatric AIDS Clinical Trials Group Protocol 076 reported a reduction in the rate of perinatal transmission of the human immunodeficiency virus (HIV) from 25.5 percent to 8.3 percent with a three-part regimen of zidovudine given ante partum, intra partum, and to the newborn. We examined the effects of abbreviated zidovudine regimens on perinatal HIV transmission using data from the HIV polymerase-chain-reaction (PCR) testing service of the New York State Department of Health. Pregnant women who received abbreviated regimens rather than the recommended regimens did so because of limited prenatal care or by choice. METHODS: The requisition form used by the PCR testing service included information on the demographic characteristics of the infants and the timing of any perinatal treatment with zidovudine. We also analyzed data on the timing of zidovudine prophylaxis collected by chart review in a subgroup of 454 infants as a means of validating the results in the entire cohort. RESULTS: From August 1, 1995, through January 31, 1997, specimens from 939 HIV-exposed infants who were 180 days of age or younger were submitted for PCR testing. The rates of perinatal HIV transmission varied depending on when zidovudine prophylaxis was begun. When treatment was begun in the prenatal period, the rate of HIV transmission was 6.1 percent (95 percent confidence interval, 4.1 to 8.9 percent); when begun intra partum, the rate was 10.0 percent (3.3 to 21.8 percent); when begun within the first 48 hours of life, the rate was 9.3 percent (4.1 to 17.5 percent); and when begun on day 3 of life or later, the rate was 18.4 percent (7.7 to 34.3 percent). In the absence of zidovudine prophylaxis, the rate of HIV transmission was 26.6 percent (21.1 to 32.7 percent). CONCLUSIONS: These results confirm the efficacy of zidovudine prophylaxis and suggest that there are reductions in the rates of perinatal transmission of HIV even with the use of abbreviated regimens that are begun intra partum or in the first 48 hours of life.     

Cost-effectiveness of a community-level HIV risk reduction intervention

OBJECTIVES: The authors evaluated the cost-effectiveness of a community-level HIV prevention intervention that used peer leaders to endorse risk reduction among gay men. METHODS: A mathematical model of HIV transmission was used to translate reported changes in sexual behavior into an estimate of the number of HIV infections averted. RESULTS: The intervention cost $17,150, or about $65,000 per infection averted, and was therefore cost-saving, even under very conservative modeling assumptions. CONCLUSIONS: For this intervention, the cost of HIV prevention was more than offset by savings in averted future medical care costs. Community-level interventions to prevent HIV transmission that use existing social networks can be highly cost-effective.     

Prenatal screening for cystic fibrosis carriers: an economic evaluation

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.     

Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks.     

The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C

OBJECTIVE: To model the costs and effects of alpha interferon in the treatment of chronic active hepatitis C. DESIGN: A Markov modelling process to simulate the costs and outcomes in hypothetical cohorts of patients treated with and without alpha interferon. OUTCOME MEASURES: Costs per life saved and per life-year gained. RESULTS: On the basis of assumptions formulated about the disease processes and response to treatment, treatment with alpha interferon results in a discounted cost per life-year gained of $33,230 in patients with cirrhosis at the start of treatment and $71,950 in patients without advanced liver disease. The result is sensitive to the assumptions made about the long term effectiveness of alpha interferon. CONCLUSIONS: Alpha interferon is an expensive drug. Its effectiveness is clouded by uncertainty about the long term impact of the drug on the natural history of the disease. If adopted, its use should be monitored to allow the long term cost effectiveness of the drug to be evaluated properly.     

Cost-effectiveness of improved treatment services for sexually transmitted diseases in preventing HIV-1 infection in Mwanza Region, Tanzania

Improved management of sexually transmitted diseases (STDs) is consistently advocated as an effective strategy for HIV prevention. The impact, cost, and cost-effectiveness of this approach were evaluated in a prospective, comparative study of six communities in Tanzania's Mwanza Region in which primary health care center workers were trained to provide improved STD treatment and six matched non-intervention communities. The baseline prevalence of HIV was 4% in both groups. During the 2-year study period, 11,632 cases of STDs were treated in the intervention health units. The HIV seroconversion rate was 1.16% in the intervention communities and 1.86% in the comparison communities--a difference in HIV incidence of 0.70 (95% confidence interval, 0.37-1.09) and a reduction of about 40%. The total annual cost of the intervention was US$59,060 ($0.39 per person served). The cost of STD treatment was $10.15 per case. An estimated 252 HIV-1 infections were averted each year. The incremental annual cost of the program was $54,839, equivalent to $217.62 per HIV infection averted and $10.33 per disability-adjusted-life-year (DALY) saved. The estimated cost-effectiveness compares favorably with that of childhood immunization programs ($12-17 per DALY saved) and could be further enhanced through implementation of the intervention on a wider scale. The intervention subsequently has been expanded to encompass 65 health units in Mwanza Region, with no increase in investment costs.     

Amprenavir

Amprenavir is a viral protease inhibitor with specificity for the HIV protease enzyme. The resistance profile of amprenavir appears to differ from that of other protease inhibitors such as saquinavir and indinavir. Twelve hours after single-dose administration of amprenavir 1200mg to HIV-infected individuals, the mean plasma concentration of the drug was more than 10-fold greater than the 50% inhibitory concentration for HIV-1IIIB in peripheral blood lymphocytes. In a small nonblind study, amprenavir monotherapy increased CD4+ cell count and decreased viral load in 37 patients with HIV infection and no previous exposure to protease inhibitor therapy. Combination therapy comprising amprenavir and other antiretroviral agents (abacavir, zidovudine, lamivudine, indinavir, saquinavir or nelfinavir) decreased viral load and increased CD4+ cell counts in patients with HIV infection. Antiviral efficacy was maintained during up to 24 weeks' follow-up. Available data suggest that rash, headache and diarrhoea or loose stools are the most frequent adverse events associated with amprenavir therapy.     

The hemodialysis prescription and cost effectiveness. Renal Physicians Association Working Committee on Clinical Guidelines

Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD increased during the 1980s, despite the introduction of advanced dialysis technologies. Variations in dialysis practices suggest that excess mortality may be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was used to assess whether attempts to improve uremic-toxin clearance are cost effective, assuming that these therapies are clinically effective. The medical literature was surveyed by the use of MEDLINE to assess the likelihood of clinical outcomes on the basis of the type of treatment given to the patient. Options considered in the model were delivered fractional urea clearance (Kt/V), dialysis-treatment duration, type of dialyzer membrane, dialysate, and ultrafiltration. Clinical outcomes included in the model were survival, severity of uremic symptoms, hospital days per year, and intradialytic hypotension and symptoms. Lifetime costs were calculated from data collected from a northern California dialysis center and abstracted from the literature. In the base-case scenario, it was assumed that increasing Kt/V to levels greater than 1 was effective in reducing morbidity and mortality. Under these assumptions, outpatient cost increased significantly, but the cost effectiveness of Kt/V equal to 1.5 was less than $50,000 per quality-adjusted life-year saved. These calculations indicate that, if higher levels of Kt/V prove clinically effective, they are also cost effective.     

Acute generalized exanthematous pustulosis: a cutaneous adverse effect due to prophylactic antiviral therapy with protease inhibitor

We describe a human immunodeficiency virus-seronegative man who presented with a skin disorder that we diagnosed as acute generalized exanthematous pustulosis, which we believe was an adverse reaction to combination prophylactic therapy with zidovudine, lamivudine, and protease inhibitor for human immunodeficiency virus. Cutaneous adverse effects are rarely reported with the use of these antiviral drugs.     

Safety and cost-effectiveness of solvent-detergent-treated plasma. In search of a zero-risk blood supply

OBJECTIVE: To determine the public health and economic implications of solvent-detergent-treated frozen plasma (SD FP). While this processing technique nearly eliminates the risk of transmitting lipid-enveloped viruses (hepatitis B and C and human immunodeficiency virus), it has associated costs and, because it requires pooling many plasma units, may increase risks of nonenveloped virus transmission. DESIGN: A previously published Markov decision analysis model was modified to assess transfusion-related outcomes in hypothetical cohorts of plasma recipients. In-hospital mortality and other characteristics were determined in 61 patients receiving plasma transfusions at a medium-sized tertiary care center to provide data for the model. Other parameters were obtained from the medical literature. MAIN OUTCOME MEASURES: Expected SD FP costs, benefits, and cost-effectiveness, assessed as cost per quality-adjusted life-year saved. RESULTS: Compared with untreated plasma, a unit of SD FP produces a net benefit of 35 minutes in quality-adjusted life expectancy at a cost of about $19. Extrapolated to the 2.2 million plasma units transfused annually in the United States, SD FP would save 147 quality-adjusted life-years at a cost of $42.5 million. The marginal cost-effectiveness, $289,300 per quality-adjusted life-year saved in the baseline analysis, was most sensitive to estimates of SD treatment cost and the clinical setting of plasma use. In sensitivity analysis, the net benefit of SD FP was negated by the existence of even a minute risk of nonenveloped virus infection. CONCLUSIONS: From a public health perspective, the relatively high costs and small benefits of reducing enveloped virus infection risks with SD FP (and the additional risks of noneveloped virus transmission) do not appear to justify widespread implementation of this new technology.