The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L.
To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates.
Prospective observational study.
Province-wide Canadian HIV/AIDS treatment program.
1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002.
Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards.
Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2).
Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun.
Comment In: Ann Intern Med. 2003 Nov 18;139(10):I2014623639
Given the recent evolution of therapeutic trends, the frequency and determinants of multiclass-resistant HIV infection in the modern combination highly active antiretroviral therapy (HAART) era are less well understood. In this study, the authors characterize the epidemiology of antiretroviral multiclass resistance among HAART-naïve patients enrolled in a province-wide HAART distribution program in British Columbia, Canada. HAART and resistance testing are free to eligible individuals in British Columbia. This study was based on patients who initiated naïve on HAART and were followed during January 1, 2000-June 30, 2007. Explanatory logistic and survival models were built to identify those factors most influential in the emergence of multiclass resistance. Among the 1,820 individuals in our study, 833 (46%) were tested for antiretroviral resistance at least once during their follow-up. Multiclass resistance was observed in 142 individuals (n = 833; 17%) during a median follow-up of 14 months (interquartile range, 3-34 months) (incidence rate, 0.8 cases/1,000 person-months). The authors found that initial nonnucleoside reverse transcriptase inhibitor-based HAART was the main determinant of multiclass resistance. Given that these inhibitors are still widely used, priority should be given to make resistance testing and viral load monitoring a standard part of human immunodeficiency virus care to maximize the long-term efficacy and efficiency of HAART.
Hunger and food insecurity are important factors that may affect an individual's nutritional state and should therefore be assessed in nutrition surveillance activities. The objective of this study was to determine the level of food insecurity and hunger among HIV-positive persons accessing antiretroviral therapy in British Columbia. A cross-sectional study was performed in the BC HIV/AIDS drug treatment program, a province-wide source of free-of-charge antiretroviral medications. In 1998-1999, participants completed a questionnaire focusing on personal information, health, and clinical status. Food and hunger issues were evaluated with the Radimer/Cornell questionnaire. Overall, 1213 responding men and women were classified as food secure (52%), food insecure without hunger (27%), or food insecure with hunger (21%). In both categories of food insecurity, individuals were significantly more likely to be women, aboriginals, living with children, and to have less education, a history of recreational injection drug and/or alcohol abuse, and an unstable housing situation (P
There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/microL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated.
We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (or=200 cells/microL) and adherence.
Among patients starting HAART with or=50 cells/microL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts 200 cells/microL (RH = 4.85, 95% CI: 3.15-7.47).
These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.
There have been limited studies evaluating temporal changes in the incidence of detection of drug resistance among human immunodeficiency virus type 1 (HIV-1) isolates and concomitant changes in plasma HIV load for treated individuals in a population-wide setting.
Longitudinal plasma viral load and genotypic resistance data were obtained from patients receiving antiretroviral therapy from the British Columbia Drug Treatment Program from July 1996 through December 2008. A total of 24,652 resistance tests were available from 5422 individuals. The incidence of successful plasma viral load suppression and of resistance to each of 3 antiretroviral categories (nucleoside/nucleotide reverse-transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors) was calculated for the population receiving therapy.
There has been a drastic decrease in the incidence of new cases of HIV-1 drug resistance in individuals followed during 1996-2008. In 1997, the incidence rate of any newly detected resistance was 1.73 cases per 100 person-months of therapy, and by 2008, the incidence rate had decreased >12-fold, to 0.13 cases per 100 person-months of therapy. This decrease in the incidence of resistance has occurred at an exponential rate, with half-times on the order of 2-3 years. Concomitantly, the proportion of individuals with plasma viral load suppression has increased linearly over time (from 64.7% with HIV RNA levels
Cites: J Infect Dis. 2005 Feb 1;191(3):339-4715633092
Cites: AIDS Res Hum Retroviruses. 2008 Jan;24(1):43-5118275347
To measure the association between intensive care unit (ICU) admission and both hospital and long-term mortality, separate from the effect of hospital admission alone.
Retrospective cohort study.
All hospitals in British Columbia, Canada, during 3 fiscal years, 1994 to 1996.
A total of 27,103 patients admitted to ICU and 41,308 (5% random sample) patients admitted to hospital but not to ICU.
Although ICU admission was an important factor associated with hospital mortality (odds ratio: 9.12; 95% confidence interval: 8.34-9.96), the association between ICU admission and mortality after discharge was relatively minimal (hazard ratio: 1.21; 95% confidence interval: 1.17-1.27) and was completely overshadowed by the effect of age, gender, and diagnosis.
After controlling for the effect of hospital admission, admission to ICU has minimal independent effect on mortality after discharge.
Comment In: Crit Care Med. 2002 Mar;30(3):703-511990940
To calculate the rate of interventional cardiac procedures (ICP) among HIV-infected individuals ever treated with antiretroviral therapy (ART) and to describe clinical and sociodemographic characteristics associated with ICP.
Since 1992, ART in British Columbia (BC) has been centrally distributed by the BC Centre for Excellence in HIV/AIDS. The BC Cardiac Registry maintains information regarding all cardiac procedures performed in BC. The two databases were linked to determine the number of HIV-positive individuals on ART who underwent ICP. Age-adjusted analyses were conducted using direct standardization, and linear regression to test for trend over time. Logistic regression was used to identify patient and treatment characteristics independently associated with having an interventional cardiac procedure.
Of the 5082 individuals who have ever received ART, 63 (
To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users.
Prospective cohort study.
Inner city community in Vancouver, Canada.
Injecting drug users, with and without HIV, followed up every six months between 1 May 1996 and 30 June 2007.
Estimated community plasma HIV-1 RNA in the six months before each HIV negative participant's follow-up visit. Associated HIV incidence.
Among 622 injecting drug users with HIV, 12 435 measurements of plasma HIV-1 RNA were obtained. Among 1429 injecting drug users without HIV, there were 155 HIV seroconversions, resulting in an incidence density of 2.49 (95% confidence interval 2.09 to 2.88) per 100 person years. In a Cox model that adjusted for unsafe sexual behaviours and sharing used syringes, the estimated community plasma HIV-1 RNA concentration remained independently associated with the time to HIV seroconversion (hazard ratio 3.32 (1.82 to 6.08, P
Cites: AIDS. 2001 Sep 7;15(13):1701-611546946
Cites: Addiction. 2006 Sep;101(9):1246-5316911723
Cites: Lancet. 2002 May 25;359(9320):1851-612044394