Mild-to-moderate symptoms during the first year of antiretroviral therapy worsen quality of life in HIV-infected individuals.

Symptoms and quality of life were assessed among human immunodeficiency virus (HIV)-infected individuals initiating their first course of antiretroviral therapy. Symptoms, which were mostly mild or moderate, were common in the first year and significantly affected the patients' quality of life. Quality of life was inversely related to the number of symptoms and in the change in the number of symptoms from baseline.

Sustained benefit from a long-term antiretroviral adherence intervention. Results of a large randomized clinical trial.

OBJECTIVE: To assess the efficacy of 2 adherence interventions, medication managers (MM) and medication alarms (ALR), among antiretroviral (ARV)-naive persons with HIV initiating ARV therapy. METHODS: A multicenter, randomized, adherence intervention clinical trial was conducted among participants coenrolled in an HIV ARV strategy study for ARV-naive individuals. Sites were assigned by cluster randomization using a 2 x 2 factorial design to administer MM, ALR, MM + ALR, or neither (control). MM participants received individualized, structured, long-term adherence support from trained MMs. ALR participants received individually programmed ALR alarms for use throughout the study. RESULTS: The 928 participants, followed a median of 30 months, included 22% women and 75% nonwhites; the median baseline CD4 count was 155 cells/mm. First virologic failure was 13% lower in all MM versus no-MM groups (P = 0.13) and 28% lower in MM versus no-MM subgroups randomized to 2-class ARV arms in the parent ARV study (P = 0.01). MM (vs. no-MM) participants had significantly better CD4 cells count (P = 0.01) and adherence (P < 0.001) outcomes. ALR (vs. no-ALR) participants had worse virologic outcomes. CONCLUSION: This large randomized clinical trial demonstrated that interpersonal structured adherence support was associated with improved long-term medication adherence and virologic and immunologic HIV outcomes.

Hepatotoxicity of rifampin and pyrazinamide in the treatment of latent tuberculosis infection in HIV-infected persons: is it different than in HIV-uninfected persons?

BACKGROUND: In 2000, results of a multinational trial demonstrated that a 2-month course of rifampin and pyrazinamide (RZ) was as effective as isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus (HIV)-infected individuals with latent tuberculosis infection (LTBI). After the release of new guidelines, the Centers for Disease Control and Prevention received reports of severe hepatotoxicity associated with the use of the RZ regimen for the treatment of LTBI in the general population. To better understand the occurrence of hepatotoxicity in an HIV-infected population, we conducted a more detailed analysis of the liver function test results obtained in the multinational trial of RZ. METHODS: At study entry, patients were required to have a bilirubin level of < or =2.5 mg/dL and both an aspartate aminotransferase (AST) level and an alkaline phosphatase level of < or =5 times the upper limit of normal. Patients with acute hepatitis were excluded. At months 1 and 2 of the study, all patients had bilirubin and AST levels measured. RESULTS: There was no difference between the RZ and INH groups with regard to AST level or bilirubin level at baseline. An increase in the AST level of > or =40 U/L was associated with the use of INH and older age; and an increase in the bilirubin level of > or =0.5 mg/dL was associated with the use of RZ, male sex, and nonwhite race (P<.05). An absolute AST level of >250 U/L occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P=.56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH recipients and 13 of 718 RZ recipients (P=.06). CONCLUSIONS: These data demonstrate very little liver injury associated with either INH or RZ in the HIV-infected subjects, leaving unclear the reasons for serious RZ-related liver damage in the general population.

Overall mortality in the program on the surgical control of the hyperlipidemias.

BACKGROUND: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a secondary intervention trial, was the only lipid/atherosclerosis randomized clinical trial that used a surgical modality--partial ileal bypass. POSCH provided solid evidence for the clinical and arteriographic benefits of lipid profile normalization. Few longterm followup reports have been published in this field. This report concerns overall mortality, the primary endpoint of POSCH, with a mean followup of 18 years (range 15.5 to 23.0 years). STUDY DESIGN: Overall mortality data were compiled from reports to the POSCH clinics, followup telephone calls, death certificates, and the US National Death Index. RESULTS: There were 144 deaths in the control group (n = 417) and 120 deaths in the intervention group (n = 421), using intent-to-treat analysis. The risk reduction in the intervention group was 0.201 (20%); the risk ratio was 0.799, or 0.8 (95% confidence intervals, 0.628 to 1.018, p = 0.07). The proportion of patients alive was 65.7% in the control group and 72.0% in the intervention group, for a difference of 6.3% in the intervention group (p = 0.05). Kaplan-Meier survival analysis (p = 0.046) and disease-free intervals analysis at 70% survival (p < 0.001) were confirmatory. The gain in life expectancy in the intervention group was 2.7 years. CONCLUSIONS: Longterm followup POSCH data demonstrate that lipid profile normalization will decrease overall mortality and will maintain a persistent and constant increase in life expectancy.

Lipid modulation and liver function tests. A report of the Program on the Surgical Control of the Hyperlipidemias (POSCH).

BACKGROUND: Statin drugs are known to cause dose-dependent abnormalities in liver function tests (LFTs), with elevations three times the upper limits of normal of the aminotransferase enzymes in up to 2.5% of patients on the highest prescribable doses. The Program on the Surgical Control of the Hyperlipidemias (POSCH) trial employed no hypocholesterolaemic drugs and used a surgical procedure, partial ileal bypass, as the intervention modality. METHODS: Serum total bilirubin, alkaline phosphatase and serum glutamic-oxaloacetic transaminase (SGOT) (equivalent to aspartate aminotransferase [AST]), were the LFTs obtained in POSCH at baseline, 3 months, annually for 5 years, and at 7 or 10 years postrandomization. RESULTS: Abnormal values were found for total bilirubin in seven of 416 control group (CG) patients (1.68%) and in 34 of 373 intervention group (IG) patients (9.16%) (P = 0.001); for alkaline phosphatase, in 28 of 378 (7.41%) and in 41 of 326 (12.58%) (P = 0.0214); and for SGOT, in 102 of 412 (24.76%) and in 161 of 372 (43.28%) (P = 0.001). Values twice the upper limit of normal occurred in 1 CG and 1 IG patient for total bilirubin and for alkaline phosphatase, and in 11 CG and 7 IG patients for SGOT (NS). Values three times the upper limit of normal did not occur in any patient for total bilirubin or alkaline phosphatase, and occurred in 3 CG and 5 IG patients for SGOT (NS). CONCLUSIONS: In POSCH, the IG demonstrated statistically significant mild increases for total bilirubin, alkaline phosphatase and SGOT levels, with no significant increases in values twice or greater the upper limits of normal.

The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials.

We prospectively studied long-term antiretroviral adherence patterns and their impact on biologic outcomes for human immunodeficiency virus (HIV)-infected participants in 2 randomized, multicenter clinical trials. For the period from baseline to month 12 of the study, participants who reported adherence levels of 100%, 80%-99%, and 0%-79% had plasma HIV RNA levels that decreased by 2.77, 2.33, and 0.67 log(10) copies/mL, respectively (P<.001), whereas their CD4 counts increased by 179, 159, and 53 cells/mm(3), respectively (P<.001). Adherence predicted nondetectable HIV RNA levels (<50 copies/mL) at 12 months of follow-up (P<.001). The HIV RNA level was nondetectable in 72% of participants who reported 100% adherence at all 4 follow-up visits, compared with 66%, 41%, 35%, and 13% of participants who reported 100% adherence at 3, 2, 1, or 0 follow-up visits, respectively (P<.001). Nonwhite race was associated with poorer adherence (P<.001), and older age was associated with better adherence (P<.001).