Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.

To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.70; 95% confidence interval [CI], 0.55-0.90; and adjusted HR, 0.76; 95% CI, 0.61-0.95, with reduced drug susceptibility cutoffs defined as 4.0-fold and 2.5-fold higher than reference virus IC(50) values, respectively). Previous protease inhibitor experience was also a significant independent predictor. Notably, drug susceptibility predicted on the basis of treatment history alone was not predictive of time to treatment failure. In this cohort, phenotypic testing results enhanced the ability to predict sustained long-term suppression of virus load.

The changing etiology of chronic diarrhea in HIV-infected patients with CD4 cell counts less than 200 cells/mm3.

PURPOSE: The purpose of this study was to evaluate the incidence and causes of chronic diarrhea in patients with AIDS over a period of time that included the pre-HAART (highly active antiretroviral therapy) era and the introduction of HAART. METHODS: The study cohort was comprised of patients receiving primary care at a university-associated outpatient HIV clinic from January 1, 1995 to December 31, 1997. Patients were identified retrospectively through a clinical database and were included in the study if their diarrhea had persisted for longer than two weeks and their CD4 cell count at time of symptoms was <200 cells/mm3. Further data were obtained by chart review. RESULTS: Over the 36-month period, the occurrence of chronic diarrhea did not change significantly, ranging from 8 to 10.5% per year in patients with CD4 cell counts <200 cells/mm3. The percentage of patients diagnosed with opportunistic infectious etiologies decreased over the three-year period from 53% (1995) to 13% (1997). The percentage of patients diagnosed with noninfectious causes increased from 32% to 70% over this same time period. CONCLUSIONS: Over the three years of the study, the incidence of chronic diarrhea in AIDS patients in our clinic did not change. The etiologies of diarrhea did change significantly, with an increased incidence of noninfectious causes and a decreased incidence of opportunistic infectious causes. This shift in etiologies coincides with the introduction and increased use of HAART in our clinic population (1996).

Declining prevalence of opportunistic gastrointestinal disease in the era of combination antiretroviral therapy.

OBJECTIVE: Opportunistic disorders (OD) are the most frequent GI manifestations of the acquired immunodeficiency syndrome (AIDS). Since the introduction of highly active antiretroviral therapy (HAART), there appears to be have been a reduction in the incidence of many of these OD; however, the effect of HAART on the prevalence of GI OD has not been well studied. METHODS: From 4/95 through 3/98, all HIV (HIV)-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histological specimens were examined by a single GI pathologist. Patients were divided into three groups based on the time of evaluation: group I: 4/95 to 3/96; group II: 4/96 to 3/97; and group III: 4/97 to 3/98. RESULTS: A total of 166 patients (90% men; mean age 36+/-10 yr; median CD4 lymphocyte count 62 cells/microl, range 2-884, median viral RNA level 1,357 copies/ml, range undetectable to 7,721,715) underwent 279 upper and/or lower endoscopies during the study period. There were no statistical differences in patients' demographics and indications for endoscopy although the CD 4 lymphocyte count was higher in group III. The percentage of patients receiving HAART at the time of endoscopy increased from 0% to 57% over the three periods (p<0.01), and the percentage of patient receiving combination antiretroviral therapy increased from 37% to 82% over the study period (p<0.01). In contrast, the prevalence of OD decreased from 69% (group I) to 13% (group III) (p<0.01), whereas the prevalence of non-OD, including a normal endoscopy increased from 31% to 87% (p<0.01). CONCLUSIONS: GI OD now seem to be an uncommon problem in HIV-infected patients undergoing endoscopy despite a low CD4 lymphocyte count, and this reduction of OD was associated with the use of HAART.

Health-related quality of life and virologic outcomes in an HIV clinic.

OBJECTIVE: The purpose of this study was to describe the relationship between viral load and health-related quality of life (HRQOL) in a cohort of persons with human immunodeficiency virus (HIV) infection. DESIGN: We evaluated HRQOL measurements in a clinical cohort of HIV-positive patients recruited from a university-associated HIV primary care clinic. HRQOL instruments included the medical outcomes survey-short form-36(MOS-SF-36) from which mental and physical component summary scores (MCS and PCS) and subscale scores were calculated. RESULTS: Significant negative associations were found between viral load and SF-36 PCS, physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), role-emotional (RE), and vitality (VT). Similar negative associations were found between CD4 cell count and SF-36 summary and subscale scores, with the notable exception of bodily pain. Multivariate analyses controlling for the effects of CD4 cell count and other clinical variables indicated viral load as an independent predictor of SF-36 PCS, RP, BP and VT scores. CONCLUSIONS: The relationship between viral load, a measure of HIV disease activity, and several dimensions of the SF-36, a patient-focused measure of HRQOL, appears to be strong and independent of CD4 cell count. These findings suggest that having a lower viral load positively impacts the quality of life of HIV-positive patients.