Early studies of highly active antiretroviral therapy (HAART) use in clinical practice suggested suboptimal rates of viral suppression. HAART regimens and expertise in the use of HAART have since evolved, and we sought to determine how virologic response to HAART has changed in clinical practice. We compared all patients who started a first HAART regimen from 1996 through 2002 in a longitudinal cohort of HIV-infected patients in care in Baltimore. There were significant improvements in suppressing HIV RNA to < 400 copies/mL, ranging from 43.8% (1996) to 72.4% (2001-2002) by 6 months and from 60.1% (1996) to 79.9% (2001-2002) by 12 months (both P < 0.01 for trend). There were also significant improvements in CD4 cell response. Over time, there was a significant increase in the use of a nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI) regimen compared with a single PI as well as an increase in the number of patients who were antiretroviral (ARV) naive. There was also a significant temporal trend from 1996 through 2002 in achieving a suppressed HIV RNA level, adjusting for being ARV naive, specific HAART regimen, CD4 cell count, HIV-1 RNA level, and demographic factors. This suggests that improved virologic response may also be attributable to other factors such as a greater focus on medication adherence, improved ARV tolerability, and ease of dosing.
"In our programme the criteria for offering ART were medical need, with no prerequisite to demonstrate adherence, making it more similar to routine programmes in industrialized countries. Virological outcomes in those who had a 12 month blood sample taken were similar to those reported from clinic cohorts in the United States , but losses from our programme are higher than reported from such cohorts, and this is a limitation of our study. "
[Show abstract][Hide abstract] ABSTRACT: Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined.
Among ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load > or = 400 copies/ml.
Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 x 10(6)/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56-8.68), viral load at baseline (OR 3.63 [95% CI 1.88-7.00] and OR 3.54 [95% CI 1.79-7.00] for 10,001-100,000 and >100,000 compared to < or = 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92-6.35]), WHO stage (OR 2.08 [95% CI 1.28-3.34] and OR 2.03 [95% CI 1.14-3.62] for stage 3 and 4 compared to stage 1-2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had > or = 1 log decrease in viral load.
Virological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.
[Show abstract][Hide abstract] ABSTRACT: The introduction of combination antiretroviral therapy (cART) into clinical practice for
the treatment of HIV in 1995-1996 has led to dramatic reductions in mortality and
morbidity. Factors linked to a positive response to therapy include a potent and
tolerable regimen, good adherence and low levels of HIV drug resistance. The aims of
this thesis were to investigate factors potentially associated with different responses to
cART measured using virological and immunological predictive markers, and also to
look at the development of toxicities to a specific regimen. The analyses were based
on data from the EuroSIDA study, which is an observational cohort of 14,310 HIV-1
infected patients from Europe, Israel and Argentina. Data collected includes
demographic history, CD4 cell counts, viral loads and details of all drugs taken.
EuroSIDA also collects viral sequence data for its resistance database.
Investigation into virological response to first-line cART across geographical regions
found evidence of variation, which was most apparent in early-cART years. Virological
response improved over calendar time in all regions, especially in East Europe.
Neither HIV-1 subtype nor transmitted drug resistance (TDR) were found to be
associated with virological response to cART, however statistical power was limited. A
significantly decreased risk of virological failure was found in patients starting efavirenz
compared with nevirapine, which did not appear to be explained by baseline drug
resistance. Finally, incidence of abacavir discontinuation due to a hypersensitivity
reaction side effect of the drug appeared to be higher in patients starting abacavir as
part of first-line therapy but decreased in recent years.
In conclusion, this thesis has compared a variety of different responses to antiretroviral
therapy across subsets of a large heterogeneous population. It is hoped that these
findings will contribute to research in monitoring trends in response to therapy and
provide insight into association with the genetic variability of the virus.
[Show abstract][Hide abstract] ABSTRACT: The one-year survival rate of adults and children with the acquired immunodeficiency syndrome (AIDS), without antiretroviral therapy, has been about 30 percent in Haiti. Antiretroviral therapy has recently become available in Haiti and in other developing countries. Data on the efficacy of antiretroviral therapy in developing countries are limited. High rates of coinfection with tropical diseases and tuberculosis, along with malnutrition and limited laboratory monitoring of therapy, may decrease the efficacy of antiretroviral therapy in these countries.
We studied the efficacy of antiretroviral therapy in the first 1004 consecutive patients with AIDS and without previous antiretroviral therapy who were treated beginning in March 2003 in Port-au-Prince, Haiti.
During a 14-month period, three-drug antiretroviral therapy was initiated in 1004 patients, including 94 children under 13 years of age. At enrollment, the median CD4 T-cell count in adults and adolescents was 131 per cubic millimeter (interquartile range, 55 to 211 per cubic millimeter); in children, a median of 13 percent of T cells were CD4-positive (interquartile range, 8 to 20 percent). According to a Kaplan-Meier survival analysis, 87 percent of adults and adolescents and 98 percent of children were alive one year after beginning treatment. In a subgroup of 100 adult and adolescent patients who were followed for 48 to 56 weeks, 76 patients had fewer than 400 copies of human immunodeficiency virus RNA per milliliter. In adults and adolescents, the median increase in the CD4 T-cell count from baseline to 12 months was 163 per cubic millimeter (interquartile range, 77 to 251 per cubic millimeter). In children, the median percentage of CD4 T cells rose from 13 percent at baseline to 26 percent (interquartile range, 22 to 36 percent) at 12 months. Treatment-limiting toxic effects occurred in 102 of the 910 adults and adolescents (11 percent) and 5 of the 94 children (5 percent).
This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.
New England Journal of Medicine 01/2006; 353(22):2325-34. DOI:10.1056/NEJMoa051908 · 55.87 Impact Factor
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