Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human ...immunodeficiency virus (HIV)-infected people.
To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1-infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe.
Prospective multicenter cohort study.
Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999.
A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients.
Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat.
Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard RH, 0.76 per log higher; 95% confidence interval CI, 0.69-0.84; P<.001) and those taking saquinavir mesylate hard gel as a single protease inhibitor (RH, 0.62; 95% CI, 0.47-0.82; P<.001) were less likely to reach undetectable HIV-1 RNA levels. Conversely, higher CD4+ lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral-naive patients (RH, 0.50; 95% CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44-0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure.
HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.
To assess the kinetics of viral replication and decay in cerebrospinal fluid (CSF), we studied the short-term effects of highly active antiretroviral therapy (HAART) on CSF HIV-1 RNA concentrations. ...In 15 HIV-positive patients, HIV RNA concentrations were measured in paired CSF and plasma/serum samples. Samples were obtained prior to and 5 to 24 days after initiation or change of HAART. The short-term effects of interruption of HAART were tested in 2 patients. Viral load was measured by the Roche Amplicor assay. During HAART, in 12 of 15 patients a significant reduction of CSF HIV RNA concentration was observed, ranging from 0.55 to 2.77 log10 (median, 1.37 log10). This was paralleled by a reduction of blood viremia ranging from 0.12 to 3.0 log10 (median, 1.65 log10). The median half-life, as calculated from the slopes of the two time-point measurements, for CSF and blood viral load was 2.66 and 2.36 days, respectively. In 2 patients, CSF viral load remained essentially unchanged despite substantial reduction of plasma viral load. In 1 patient, after interruption of HAART, a rapid increase of HIV RNA in the CSF and blood was seen. No correlation was found between the CSF:blood albumin ratio as a measure of the functional integrity of the blood-CSF barrier and the ratio of CSF:blood RNA concentration, which suggests that no major passive influx of HIV RNA moves from the blood into the CSF compartment. However, a correlation existed between the CSF cell count and the CSF viral load (r = 0.74; p < .003). We conclude that, in most HIV-infected individuals, the decay of viral load in the CSF is similarly rapid as that seen in plasma. The rapid kinetics of virus found in the CSF suggest that it may be produced by rapidly proliferating cells, such as lymphocytes.
Glycoprotein B (gB) is involved in cell to cell transmission of human cytomegalovirus (HCMV) and may be a critical factor in tissue tropism and viral pathogenesis. We analyzed the distribution of the ...four known gB genotypes of HCMV in 99 HIV-positive patients. 29 patients had HCMV retinitis, and 70 patients had asymptomatic HCMV infection. DNA was isolated from blood, urine, and aqueous humor, and gB genotypes were determined by PCR and restriction analysis. Infections with gB type 1 were less frequent in patients with retinitis than in patients with asymptomatic HCMV infection (17% versus 37%; p = 0.05). Furthermore, the gB type was correlated with dissemination of infection. In patients with HCMV detected in only one compartment (blood or urine) the gB type 1 was found more frequently than in patients with HCMV detected in at least two compartments (p = 0.01). The data show that gB genotypes differ in their association with clinical disease, and indicate that the gB genotype may contribute to the course of HCMV infection.
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