Biomedical subjects
Publications and source records attributed to Paul E Sax.
We report the case of a patient with AIDS who developed retroviral rebound syndrome that led to death after antiretroviral therapy was stopped because of toxicity. Cases of retroviral rebound syndrome reported in the literature are briefly reviewed.
BACKGROUND: Data from the United States and Europe show a population prevalence of baseline drug resistance of 8%-10% among human immunodeficiency virus (HIV)-infected patients who are antiretroviral naive. Our objective was to determine the clinical impact and cost-effectiveness of genotype resistance testing for treatment-naive patients with chronic HIV infection. METHODS: We utilized a state-transition model of HIV disease to project life expectancy, costs, and cost-effectiveness in a hypothetical cohort of antiretroviral-naive patients with chronic HIV infection. On the basis of a US survey of treatment-naive patients from the Centers for Disease Control and Prevention, we used a baseline prevalence of drug resistance of 8.3%. RESULTS: A strategy of genotype-resistance testing at initial diagnosis of HIV infection increased per-person quality-adjusted life expectancy by 1.0 months, with an incremental cost-effectiveness ratio of 23,900 dollars per quality-adjusted life-year gained, compared with no genotype testing. The cost-effectiveness ratio for resistance testing remained less than 50,000 dollars per quality-adjusted life-year gained, unless the prevalence of resistance was < or =1%, a level lower than those reported in most regions of the United States and Europe. In sensitivity analyses, the cost-effectiveness remained favorable through wide variations in baseline assumptions, including variations in genotype cost, prevalence of resistance overall and to individual drug classes, and sensitivity of resistance testing. CONCLUSIONS: Genotype-resistance testing of chronically HIV-infected, antiretroviral-naive patients is likely to improve clinical outcomes and is cost-effective, compared with other HIV care in the United States. Resistance testing at the time of diagnosis should be the standard of care.
OBJECTIVE: Enfuvirtide (ENF) has been shown to improve short-term virologic responses when given to highly treatment-experienced patients with advanced HIV disease. Because of the high cost of ENF compared with other antiretroviral agents, our objectives were to determine the potential long-term clinical impact and cost-effectiveness of ENF in these patients. METHODS: We used a computer simulation model of HIV disease to project life expectancy, quality-adjusted life expectancy, cost, and cost-effectiveness of ENF in treatment-experienced patients. Input data were from the T-20 versus Optimized Regimen Only (TORO) 1 and 2 trials, 2 studies comparing ENF plus an optimized background regimen (OBR) with an OBR alone. RESULTS: ENF plus an OBR increased projected discounted quality-adjusted life expectancy from 45.4 months with an OBR alone to 54.9 months, a difference of 9.5 quality-adjusted life-months. At the current annual ENF cost of US 18,500 dollars per year (in 2001 US dollars), the incremental cost-effectiveness ratio for ENF plus an OBR was US 69,500 dollars per quality-adjusted life-year (QALY) compared with an OBR alone. When 48-week virologic suppression rates for ENF plus an OBR were varied from a 50% reduction to a 250% increase in the suppression rate attributable to ENF, gains in quality-adjusted life expectancy ranged from 4.5 to 25.9 quality-adjusted life-months compared with an OBR alone, with cost-effectiveness ratios ranging from US 97,900 dollars per QALY to US 52,300 dollars per QALY gained. If ENF is continued after the HIV RNA level returns to the pretreatment baseline, the cost-effectiveness ratio increases to US 168,200 dollars per QALY. CONCLUSIONS: In highly treatment-experienced patients, ENF plus an OBR provides substantial gains in quality-adjusted life expectancy compared with an OBR alone. Although ENF plus an OBR is less cost-effective than other commonly used interventions in HIV disease, its use may be justified, given the poor prognosis of these patients and their otherwise limited options for antiretroviral therapy.
BACKGROUND: Whether human immunodeficiency virus type 1 (HIV-1)-positive subjects who test positive for isolated antibody to hepatitis B core antigen (anti-HBc) should be vaccinated with hepatitis B vaccine is not certain. Development of an anamnestic response after vaccination would suggest previous hepatitis B virus (HBV) infection, in which case vaccination is not necessary. METHODS: Sixty-nine HIV-1-positive subjects who tested negative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) received vaccination with standard hepatitis B vaccine. Twenty-nine subjects (42%) tested positive for anti-HBc, and 40 (58%) tested negative for anti-HBc. An anamnestic response was defined as an anti-HBs titer of >or=10 IU/L within 4 weeks of the first vaccination. RESULTS: The overall anamnestic response rate was 16% and was not significantly different between subjects who tested positive for anti-HBc (24%) and those who tested negative for anti-HBc (10%) before vaccination (P=.18). Approximately 50% of subjects who tested positive for anti-HBc also tested positive for antibody to hepatitis Be antigen (anti-HBe). The anamnestic response rate was higher in subjects who tested positive for both anti-HBc and anti-HBe (43%) than in subjects who tested positive for anti-HBc but negative for anti-HBe (7%) (P=.035). After a complete series of vaccinations, HIV-1/hepatitis C virus (HCV)-coinfected subjects were less likely to achieve high anti-HBs titers than were subjects infected with HIV-1 alone. CONCLUSIONS: After hepatitis B vaccination, the anamnestic response rate in HIV-1-positive subjects who tested positive for isolated anti-HBc but negative for anti-HBe was low and was comparable to that in subjects who tested negative for anti-HBc. This finding suggests that testing for anti-HBc alone may not be a reliable assessment of protection from HBV infection. HIV-1/HCV coinfection may be associated with impaired responses to hepatitis B vaccine, and evaluation of strategies to improve immunogenicity of the vaccine in such individuals is warranted.
BACKGROUND: The Centers for Disease Control and Prevention guidelines recommend human immunodeficiency virus (HIV) counseling, testing, and referral for all patients in hospitals with an HIV prevalence of >or=1%. The 1% screening threshold has not been critically examined since HIV became effectively treatable in 1995. Our objective was to evaluate the clinical effect and cost-effectiveness of current guidelines and of alternate HIV prevalence thresholds. METHODS: We performed a cost-effectiveness analysis using a computer simulation model of HIV screening and disease as applied to inpatients in U.S. hospitals. RESULTS: At an undiagnosed inpatient HIV prevalence of 1% and an overall participation rate of 33%, HIV screening increased mean quality-adjusted life expectancy by 6.13 years per 1000 inpatients, with a cost-effectiveness ratio of 35,400 dollars per quality-adjusted life-year (QALY) gained. Expansion of screening to settings with a prevalence as low as 0.1% increased the ratio to 64,500 dollars per QALY gained. Increasing counseling and testing costs from 53 dollars to 103 dollars per person still yielded a cost-effectiveness ratio below 100,000 dollars per QALY gained at a prevalence of undiagnosed infection of 0.1%. CONCLUSION: Routine inpatient HIV screening programs are not only cost-effective but would likely remain so at a prevalence of undiagnosed HIV infection 10 times lower than recommended thresholds. The current HIV counseling, testing, and referral guidelines should now be implemented nationwide as a way of linking infected patients to life-sustaining care.
Combination antiretroviral therapy (ART) with two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) significantly improved the prognosis of patients with HIV. Nevertheless, the usefulness of the first PIs was sometimes compromised by poor tolerability, high pill burden, frequent dosing, and food and fluid restrictions. Consequently, initial ART choices evolved toward simpler PI-sparing regimens incorporating non-nucleoside reverse transcriptase inhibitors or triple NRTIs. Because these PI-sparing alternatives also are imperfect, interest in PI-based approaches to initial therapy remains, especially in light of newer PIs that have a more favorable tolerability profile. The better safety and tolerability attributes of the newer PIs suggest that highly effective therapy can be administered while preserving patients' health-related quality of life. As long as the virologic activity of these newer PIs is comparable to that of existing options, differentiating features beyond efficacy are important in the choice of an appropriate treatment regimen for patients with HIV.
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OBJECTIVE: Clinicians are increasingly challenged by presentation of morphologic and metabolic complications in HIV-infected patients. These complications are associated with HIV infection and/or combination antiretroviral therapy. This Consensus Statement is intended to offer guidance to clinicians actively involved in HIV/AIDS care. PARTICIPANTS: Seven clinicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee. CONSENSUS PROCESS: IAPAC convened the Advisory Committee to develop a draft Consensus Statement. Each clinician was tasked with drafting a specific section of the Consensus Statement corresponding with his or her expertise around a morphologic and/or metabolic complication. Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence. This document represents the consensus agreement of the Advisory Committee.
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New studies address the optimal duration of HCV treatment, early predictors of treatment response, and risk factors for liver-related mortality.
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