Higher HIV-1 RNA Levels Research Articles

Biological and virologic characteristics of primary HIV infection.

The clinical events surrounding acute HIV-1 infection have been well described, but little is known about whether the virologic course of acute HIV-1 infection influences the subsequent progression of disease. To define the virologic natural history of acute and very early HIV infection. Prospective, longitudinal cohort study. University of Washington Research Clinic 74 adults enrolled soon after acquisition of HIV (mean, 69 days). Plasma HIV-1 RNA levels; quantitative cell cultures; CD4 cell counts; and detailed clinical assessments done at study entry, biweekly for 1 month, monthly for 2 months, and quarterly thereafter. In the first 30 days after acquisition of HIV, HIV-1 RNA levels varied greatly among participants (range, 27,200 to 1.6 x 10(6) copies per mL of plasma). Levels of HIV-1 RNA decreased by a mean of 6.5% per week for the first 120 days and then increased by a mean of 0.15% per week. CD4 cell counts decreased by a mean of 5.2 cells/mm3 per week for the first 160 days and by a mean of 1.9 cells/mm3 per week thereafter (P < 0.01). Disease progressed faster in participants who sought medical care for their acute seroconversion syndrome (P = 0.01) and those who had high plasma HIV-1 RNA levels 120 to 365 days after acquisition (P < 0.01). Peak levels in the first 120 days were not predictive of disease progression. The variability in viral RNA levels associated with acute HIV-1 infection is greater than previously appreciated. Within 120 days of acquisition, plasma HIV RNA levels rapidly decrease to an inflection point, after which they gradually increase. Virus-host interactions soon after acquisition seem to have a major influence on the long-term outcome of HIV-1 disease.

Unintegrated circular HIV-1 DNA in the peripheral mononuclear cells of HIV-1-infected subjects: association with high levels of plasma HIV-1 RNA, rapid decline in CD4 count, and clinical progression to AIDS.

We observed 36 HIV-infected patients to evaluate whether the presence of tandem 2-long terminal repeat circular unintegrated HIV-1 DNA (2-LTR) in peripheral blood mononuclear cells (PBMC) at baseline was associated with acceleration of HIV disease. Detection of 2-LTR at baseline correlated with high plasma HIV-1 RNA levels (p < .01), recovery of culturable HIV-1 from plasma (p = .02), and progression to AIDS during follow-up (p = .01). More patients with 2-LTR (68%) than without 2-LTR (31%) had a decline in CD4 levels of >50 cells/mm3 over the first 18 months of follow-up (p = .04), and the average annual CD4 decline was 35% in patients with 2-LTR compared with 16% in those without 2-LTR (p = 0.06). Detection of 2-LTR in PBMC at baseline was an independent predictor of high plasma HIV-1 RNA levels and subsequent CD4 cell decline in this cohort of patients with predominantly nonsyncytium-inducing (NSI) isolates at baseline. The presence of 2-LTR in PBMC appears to be reflective of ongoing HIV-1 replication, as measured by plasma HIV-1 RNA levels, and identifies persons at risk for immunologic and clinical decline.

Dose of Non-Heat-Treated Factor VIII Concentrate and HIV-1 RNA Levels-Reply

In Reply. —Dr Montoro and colleagues recategorized our data and used a test for linear trend instead of the more conservative overall Mantel-Haenszel ϰ2test that we used. They point out that subjects who received lower annual doses of non-heat-treated factor VIII concentrate (between 1978 and 1984) had somewhat higher HIV-1 RNA levels. An association between lower factor VIII dose and higher HIV-1 RNA levels would be consistent with a recent report by Montoro et al that lower factor-concentrate dose was associated with faster progression to AIDS in 225 HIV-1-infected Spanish hemophiliac patients.1Therefore, we examined the relationship between factor VIII dose, HIV-1 RNA levels, and time to development of AIDS in our study, the Multicenter Hemophilia Cohort Study (MHCS). Although only a small subset of MHCS subjects were tested for HIV-1 RNA, data on factor VIII dose and clinical outcome were available for 1094 HIV-1-infected adults and children. As

Response of HIV RNA to didanosine as a predictive marker of survival

Objective: To evaluate whether early changes in viraemia in response to didanosine (ddl) predict death and occurrence of new AIDS-defining events. Methods: Forty-three patients were followed during ddl treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddl therapy. Results: After 1 month of ddl, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P<0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P=0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P=0.018) was observed. After stratification for presence of AIDS before starting ddl, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P=0.0006 and P=0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P=0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P=0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. Conclusions: In patients treated with ddl, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.

Response of HIV RNA to didanosine as a predictive marker of survival

To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.