Factors associated with non-adherence to antiretroviral therapy in the SUN study.

BACKGROUND: Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. METHODS: We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. RESULTS: Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm(3)), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20-3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14-3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18-3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25-3.57). CONCLUSION: Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.

Renal function in patients with preexisting renal disease receiving tenofovir-containing highly active antiretroviral therapy in the HIV outpatient study.

Few data exist on the safety of tenofovir (TDF) in HIV-infected patients with preexisting renal dysfunction. We report 12-month changes in renal profiles among 19 such patients (6 patients with history of and 13 patients with current renal disease) in the HIV Outpatient Study (HOPS) who initiated TDF-containing highly active antiretroviral therapy (HAART) during 2001-2005 with TDF dosed mostly at 300 mg once daily. At baseline, the median estimated glomerular filtration rate (GFR) was 49 mL/min/1.73 m(2) and the median CD4(+) cell count was 322 cells/mm(3). Patients had a median 12-month change in estimated creatinine clearance from baseline of -0.3 mL/min (range, -32.2 to +23.6) and the median change in GFR of -0.1 mL/min/1.73 m(2) (range, -49.8 to +29.5). We observed confirmed worsening of kidney disease stage in 5 of the 19 patients during follow-up. TDF use can be considered in patients with preexisting or current renal dysfunction who have limited antiretroviral treatment options, require TDF for fully active antiretroviral regimen, and can be closely monitored for incident worsening of renal function.

Renal function in Tenofovir-exposed and Tenofovir-unexposed patients receiving highly active antiretroviral therapy in the HIV Outpatient Study.

BACKGROUND: Cases of renal dysfunction have been reported in HIV-infected patients taking tenofovir (TDF), but few large studies have examined population-level changes in renal function associated with TDF use in patients in routine care. METHODS: The authors analyzed data from participants in the HIV Outpatient Study (HOPS) who had normal baseline renal function and received >1 month of TDF-containing (n = 593) or TDF-sparing (n = 521) HAART after November 1, 2001. RESULTS: Median baseline CrCl estimated by Cockcroft-Gault equation was 106 mL/min for TDF-exposed and 110 mL/min for TDF-unexposed patients (P = 0.06). In multivariable analyses, 1-year changes in CrCl (mL/min) from baseline were -5.7 among TDF-exposed and 2.6 among TDF-unexposed (P < 0.001). Incident renal disease was diagnosed in 7 TDF-exposed and 3 TDF-unexposed patients. CONCLUSIONS: In this large cohort of HIV-infected outpatients, use of TDF-containing HAART was associated with modest decreases in CrCl during the first year, but not with frequent, clinically significant renal toxicity.

Factors related to and consequences of adherence to antiretroviral therapy in an ambulatory HIV-infected patient cohort.

In a confidential medication adherence questionnaire completed by 255 participants in the HIV Outpatient Study (HOPS) between March and November 1999, 33% reported skipping antiretroviral doses within the previous 3 days. The respondents, with a median age of 41, were predominantly male (86%), white (62%), and highly educated (33% had some post-high school training but no college degree and 39% had a college degree; only 11% had less than a high school diploma). Twenty-one percent had a history of injection drug use, 12% were unemployed, and 18% had Medicaid insurance. Questions about difficulty taking antiretroviral medications or drug holidays identified an additional 16% of patients experiencing adherence problems and explained significantly more of the failure to achieve undetectable viral loads than simply querying about skipped doses.

Factors associated with maintenance of long-term plasma human immunodeficiency virus RNA suppression.

To analyze factors associated with long-term (>or=2 years) suppression of virus load (VL), we performed a nested case-control analysis of 1235 Human Immunodeficiency Virus Outpatient Study cohort participants who were well characterized by multiple VL and CD4(+) cell count determinations. Of these patients, 286 (23.1%) had maintained undetectable VLs (i.e., <400 copies/mm(3) or <50 copies/mm(3)) for >or=2 years. Being treatment naive at the start of antiretroviral therapy was associated with a greater likelihood of achieving long-term suppression of VL (odds ratio [OR], 1.5; 95% confidence interval, 1.0-2.0; P=.028). In multivariate models, abacavir, indinavir, efavirenz, and drug combinations that included both lamivudine and indinavir were the most effective treatments for achieving long-term suppression of VL (adjusted OR for each, >3.6; P value for each, <.01). Long-term suppression of VL is more likely in treatment-naive than in treatment-experienced patients, but there were several drugs--abacavir, efavirenz, indinavir, and drug combinations including lamivudine and indinavir--that appeared to be effective, whether they were part of a first or subsequent drug regimen.

Protease inhibitors and cardiovascular outcomes in patients with HIV-1.

Protease inhibitors for treatment of HIV-1 have been linked with increased risk of hyperlipidaemia and hyperglycaemia. In a cohort of 5672 outpatients with HIV-1 seen at nine US HIV clinics between January, 1993, and January, 2002, the frequency of myocardial infarctions increased after the introduction of protease inhibitors in 1996 (test for trend, p=0.0125). We noted that 19 of 3247 patients taking, but only two of 2425 who did not take, protease inhibitors had a myocardial infarction (odds ratio 7.1, 95% CI 1.6-44.3; Cox proportional hazards model-adjusted for smoking, sex, age, diabetes, hyperlipidaemia, and hypertension-hazard ratio 6.5, 0.9-47.8). Our findings suggest that, although infrequent, use of protease inhibitors is associated with increased risk of myocardial infarction in patients with HIV-1.