共查询到20条相似文献,搜索用时 31 毫秒
1.
2.
3.
OBJECTIVE: To determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads. DESIGN: Observational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA). SETTING: General Clinical Research Center at a tertiary care center. PARTICIPANTS: Forty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia. MAIN OUTCOME MEASURES: The primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads. RESULTS: Adherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84-96%], whereas detectable subjects took a median of 70% (IQR 46-93%). Adherence correlated with viral load decrease (Spearman's rho = 0.38, P < 0.01) and CD4 cell count increase (Spearman's rho = 0.25, P = 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88-98%) versus detectables, 94% (IQR 87-98%), P > 0.50]. CONCLUSIONS: Adherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important. 相似文献
4.
Prevalence and clinical correlates of HIV viremia ('blips') in patients with previous suppression below the limits of quantification 总被引:5,自引:0,他引:5
Sklar PA Ward DJ Baker RK Wood KC Gafoor Z Alzola CF Moorman AC Holmberg SD;HIV Outpatient Study 《AIDS (London, England)》2002,16(15):2035-2041
OBJECTIVE: To examine the prevalence and clinical correlates of subsequently measurable viremia in HIV-infected patients who have achieved viral suppression below the limits of quantification (< 50 copies/ml). DESIGN: Non-randomized dynamic cohort study of ambulatory HIV patients in nine HIV clinics in eight cities. PATIENTS: Patients had two consecutive HIV-1 RNA levels < 50 copies/ml (minimum, 2 months apart) that were followed by at least two more viral level determinations while remaining on the same antiretroviral therapy (ART) between January 1997 and June 2000 (median 485 days). Transiently viremic patients were defined having a subsequently measurable viremia but again achieved suppression < 50 copies/ml. RESULTS: Of the 448 patients, 122 (27.2%) had transient viremia, 19 (4.2%) had lasting low-level viremia and 33 (7.4%) had lasting high-level viremia (defined as 50-400 and > 400 copies/ml, respectively). Only 16 (13.1%) of those who had transient viremia later had persistent viremia > 50 copies/ml. The occurrence of transient viremia did not vary with whether the patient was ART-naive or experienced (P = 0.31), or currently taking protease inhibitors or not (P = 0.08). On consistent ART, the median percentage increase in CD4 cell count was statistically different between subgroups of our cohort (Kruskal-Wallis, P = 0.002). CONCLUSIONS: Transiently detectable viremia, usually 50-400 copies/ml, was frequent among patients who had two consecutive HIV-1 RNA levels below the limits of quantification. In this analysis, such viremia did not appear to affect the risk of developing lasting viremia. Caution is warranted before considering a regimen as 'failing' and changing medications. 相似文献
5.
The objective of this study was to determine if a lower rate of adherence (<95%) is sufficient to maintain HIV viral suppression in patients on an efavirenz-based regimen. This study was a retrospective review of pharmacy refill records at an HIV specialty pharmacy at Montefiore Medical Center's outpatient clinic. Data from 151 HIV-positive patients on an efavirenz-based regimen with at least one undetectable viral load (HIV RNA < 400 copies/mL) from December 2003 through March 2005 were reviewed. Adherence was calculated based on the formula: [(pills dispensed/pills prescribed per day/days between refills)x100%]. Calculated adherence for each time-period was correlated to the respective HIV-RNA value for that period. Of 151 patients, viral suppression was maintained in greater than 80% of time periods for adherence rates as low as 85-90%. The periods with 75-80% adherence also had higher than 85% suppression. Rates of suppression began to fall when adherence decreased to < 75%. In conclusion, lower adherence rates (<95%) on an efavirenz-based regimen were more successful in maintaining viral suppression than previously found with unboosted protease inhibitor-based regimens. 相似文献
6.
Ultrasensitive assays for HIV RNA have identified a significant number of patients with persistent low-level viremia despite antiretroviral therapy. The clinical implications of maintaining antiretroviral therapy during low-level HIV viremia remain unclear. The primary objective of this study was to determine the rate and risk factors for virological increase in subjects with low-level HIV viremia who did not change antiretroviral therapy. Between July 1998 and February 2002, we retrospectively observed 79 HIV-infected adults with low-level HIV viremia (between 50 and 500 copies per milliliter) who had been on a stable antiretroviral regimen for at least 3 months and continued that regimen for at least 3 more months. Virologic increase, defined as HIV RNA levels greater than 1000 copies per milliliter, was observed in 29 of the 79 (37%) subjects. The CD4 cell counts decreased by a median of 1.8 cells/mm(3) per month (interquartile range [IQR], -19.6 to 2.3 cells/mm3) in this group but increased by a median of 0.5 cells/mm3 per month (IQR, -6.3 to 5.8 cells/mm3) in the 50 subjects who did not experience virologic increase. A Kaplan-Meier estimate showed that at 3 years of follow-up, approximately 40% of the observed cohort had not experienced virologic increase. There was a higher rate of virologic increase per log increase in HIV viral load at entry into the cohort (adjusted hazards ratio [HR] 3.7; 95% confidence interval [CI], 1.1 to 12.6). Subjects of white race were also more likely to experience virological increase (adjusted HR 2.6; CI, 1.2 to 5.8). Maintenance of antiretroviral therapy despite low-level HIV viremia provided sustained immunological benefit over a 2-year period in approximately two thirds of our cohort. Higher initial HIV RNA levels and white race were predictors for virologic increase. 相似文献
7.
Havlir DV Koelsch KK Strain MC Margot N Lu B Ignacio CC Miller MD Wong JK;Gilead Study Team 《The Journal of infectious diseases》2005,191(7):1164-1168
In human immunodeficiency virus (HIV)-infected patients successfully treated with highly active antiretroviral therapy (HAART), a low level of HIV RNA persists in plasma at steady state for years and varies among patients. To understand predictors of residual viremia, we measured HIV RNA levels <50 copies/mL in patients after 1 year of treatment with efavirenz and lamivudine plus either tenofovir disoproxil fumarate (n=55) or stavudine (n=45), by use of an HIV RNA assay with a limit of detection of 2.5 copies/mL. The mean posttreatment HIV RNA levels were 0.58 log(10) copies/mL (3.8 copies/mL) in the tenofovir arm and 0.61 log(10)copies/mL (4.1 copies/mL) in the stavudine arm (P=.24). Forty-seven percent of patients receiving tenofovir, compared with 29% of patients receiving stavudine, had undetectable residual viremia (P=.07). In multivariate analyses, we found that lower baseline HIV RNA levels in plasma, lower HIV DNA levels in peripheral blood mononuclear cells, and inclusion in the tenofovir arm each independently predicted undetectable residual viremia (P<.05). However, a level of residual viremia <50 copies/mL was not associated with CD4 cell count changes or risk of virologic rebound through 72 weeks of follow-up. 相似文献
8.
9.
BACKGROUND: Anti-retroviral drug therapy reduces but does not abolish HIV transmission and replication throughout the body. HIV DNA 2-long terminal repeat (2-LTR) circles have been shown in point-based studies to persist in some patients whose plasma HIV RNA was undetectable. However, the degree of fluctuation of circle copy number over time has not been determined. METHODS: A reliable, reproducible and robust quantitative LightCycler (LC qPCR)-based assay for HIV DNA 2-LTR circles in peripheral blood mononuclear (PBMN) cells was established. A prospective, longitudinal study of these circles was undertaken in HIV-1-positive patients on anti-retroviral therapy whose plasma HIV RNA was undetectable at < 50 copies/ml. Patients starting therapy for the first time were also monitored. RESULTS: A cohort of 60 patients whose plasma HIV RNA was undetectable for 32 +/- 2 months were monitored for circles for 15 +/- 2 months. The circle copy number ranged from < 10 to 620 copies/106 PBMN cells. The circle-negative (< 10 copies/1 x 106 PBMN) cells group of 36 patients and the circle-positive (> 10 copies/106 PBMN cells) group of 24 patients were mutually exclusive (P < 0.0001). The mean circle half-life in seven of the 10 patients starting anti-retroviral therapy for the first time was 5.7 days. CONCLUSION: The circle assay is useful for identifying those patients in whom transmission of infectious virus continues despite prolonged periods of time during which plasma HIV RNA is undetectable. New drug combinations and new therapeutic approaches should be aimed at those patients whose plasma HIV RNA is undetectable but who remain positive for 2-LTR circles. 相似文献
10.
Ostrowski SR Katzenstein TL Thim PT Pedersen BK Gerstoft J Ullum H 《The Journal of infectious diseases》2005,191(3):348-357
BACKGROUND: Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. METHODS: For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels =200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months. RESULTS: During follow-up, 33 patients had HIV RNA levels =20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05). CONCLUSION: These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART. 相似文献
11.
High levels of adherence do not prevent accumulation of HIV drug resistance mutations 总被引:9,自引:0,他引:9
Bangsberg DR Charlebois ED Grant RM Holodniy M Deeks SG Perry S Conroy KN Clark R Guzman D Zolopa A Moss A 《AIDS (London, England)》2003,17(13):1925-1932
OBJECTIVES: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence. METHODS: Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2. RESULTS: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%). CONCLUSION: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance. 相似文献
12.
To pilot the adherence readiness program, 60 patients planning to start HIV antiretrovirals were assigned to usual care (n = 31) or the intervention (n = 29), of whom 54 started antiretrovirals and were followed for up to 24 weeks. At week 24, the intervention had a large effect (50.0 % vs. 16.7 %, d = 0.75) on optimal dose-timing (85+ % doses taken on time) and small effect (54.2 % vs. 43.3 %, d = 0.22) on optimal dose-taking (85+ % doses taken) electronically monitored adherence, and medium effect on undetectable viral load (62 % 0.5 % vs. 43.4 %, d = 0.41), compared to usual care. These intervention benefits on adherence and viral suppression warrant further investigation. 相似文献
13.
14.
Flynn PM Rudy BJ Lindsey JC Douglas SD Lathey J Spector SA Martinez J Silio M Belzer M Friedman L D'Angelo L Smith E Hodge J Hughes MD;PACTG Study Team 《AIDS research and human retroviruses》2007,23(10):1208-1214
The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents. 相似文献
15.
Smith CJ Sabin CA Youle MS Kinloch-de Loes S Lampe FC Madge S Cropley I Johnson MA Phillips AN 《The Journal of infectious diseases》2004,190(10):1860-1868
BACKGROUND: Highly active antiretroviral therapy (HAART) results in an improvement in immunologic function. We sought to investigate the factors associated with increases in CD4 cell count among human immunodeficiency virus (HIV)-positive antiretroviral-naive patients starting HAART. METHODS: Five hundred ninety-six subjects were followed for a median of 2.5 years (interquartile range, 1.0-4.0 years). Factors associated with changes in CD4 cell counts in the first 3 months of HAART and from 3 months onwards were analyzed. RESULTS: After 6, 12, and 24 months of HAART, the median increases in CD4 cell counts were 114, 181, and 248 cells/mm3, respectively; 84%, 84%, and 80% of subjects had a virus load of <400 copies/mL during the same periods. White ethnicity, higher pre-HAART virus load, and lower pre-HAART CD4 and CD8 cell counts were associated with greater increases in CD4 cell counts during the first 3 months of HAART. From 3 months onward, a greater cumulative proportion of time spent with virus load <400 copies/mL was associated with a more favorable change in CD4 cell count (an average increase of 5.2 cells/mm3/year [95% confidence interval [CI], 3.8-6.7 cells/mm3/year] for each extra 10% cumulative time spent with a virus load <400 copies/mL) (P<.0001). For every 100 cells/mm3 higher in baseline CD4 cell count, the increase was 6 cells/mm3/year less (95% CI, 2-11 cells/mm3/year) (P=.02). Sex, risk group, age, and HAART regimen were not associated with increases in CD4 cell counts. CONCLUSIONS: These findings emphasize the importance of maintaining virological suppression and suggest other factors that influence long-term CD4 cell response. 相似文献
16.
Lafeuillade A Poggi C Hittinger G Counillon E Emilie D 《The Journal of infectious diseases》2003,188(10):1426-1432
Thirty patients with acute human immunodeficiency virus (HIV) type 1 infection received a combination of 3 antiretroviral drugs (n=15) or 4 antiretroviral drugs plus hydroxyurea and interleukin-2 (n=15) for 24 months, followed by 1-3 structured therapeutic interruptions (STIs). Viral control, defined as maintaining plasma viremia <5000 copies/mL without therapy, was achieved in 14 cases. Lymphocyte subsets, plasma HIV-1 RNA loads, proviral DNA loads in peripheral blood mononuclear cells (PBMCs), residual HIV-1 RNA loads in PBMCs and in lymph node cells, and anti-p24 lymphoproliferative response were measured. In the multivariate analysis, proviral DNA loads in PBMCs and anti-p24 lymphoproliferative response assessed at 24 months were independently correlated with viral control after STI. These results enabled us to define a subgroup of patients for whom safe discontinuation of therapy initiated at acute infection was suitable and contributed to ascertaining priority for biological parameter assessment in future clinical trials. 相似文献
17.
Para MF Kalish LA Collier AC Murphy EL Drew WL;Viral Activation Transfusion Study Group 《The Journal of infectious diseases》2001,183(11):1673-1677
The Viral Activation Transfusion Study compared leukocyte-reduced to unfiltered red blood cell transfusions in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-coinfected patients. Relationships between serially measured plasma CMV load and clinical and laboratory outcomes over a median of 12 months were examined in 511 subjects. At baseline, subjects had a median of 15 CD4(+) cells/mm(3), 25% had CMV disease, and 21.5% were viremic. No relationship was found between changes in CMV viremia and changes in HIV RNA. Increased CMV viremia was associated with a concomitant fall in Karnofsky score. Highly active antiretroviral therapy (HAART) led to a decrease in CMV viremia after a 90-day delay. After adjustment for HIV load and CD4(+) cell count, CMV viremia remained associated with an increased risk of CMV disease (relative hazard, 5.78). In late-stage HIV-infected patients, CMV viremia was associated with lower functional status and increased risk of CMV disease. HAART suppressed CMV viremia only after a delay of several months. 相似文献
18.
Morris L Martin DJ Bredell H Nyoka SN Sacks L Pendle S Page-Shipp L Karp CL Sterling TR Quinn TC Chaisson RE 《The Journal of infectious diseases》2003,187(12):1967-1971
During 6 months of treatment, we measured human immunodeficiency virus (HIV)-1 virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1-infected patients with active tuberculosis (TB). The median virus load (baseline, 5.58 log(10) copies/mL) significantly increased at 1 month (5.71 log(10) copies/mL), then returned to near-baseline levels at 3 months (5.40 log(10) copies/mL) and at 6 months (5.36 log(10) copies/mL). In contrast, the median CD4 counts increased at 1 month (186/mm(3)), at 3 months (238/mm(3)), and at 6 months (239/mm(3)). CD4 counts and virus loads did not change during therapy. Expression of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of interleukin-6 decreased over time. 相似文献
19.
Bedimo R Chen RY Westfall AO Raper JL Allison JJ Saag MS 《AIDS research and human retroviruses》2006,22(1):40-44
Treatment of HIV-infected patients with HAART can result in long-term suppression of viral loads to undetectable levels. Rapid virologic rebound typically follows treatment interruption (TI), with a potential for significant loss of CD4+ cells. Patients who maintain virologic suppression despite interrupting treatment have not been well described. All patients with a pretreatment viral load (VL) > or = 5000 copies/ml, who had been on therapy for > or = 2 weeks, and who underwent a TI lasting > or = 180 days were analyzed. Patients whose maximum VL did not exceed 5000 copies/ml > or = 6 months after starting TI ("nonrebounders") were compared with those whose VL exceeded 5000 copies/ml (rebounders). Seventy-one patients were included in the analysis. Nineteen (27%) were nonrebounders. Ninety-four percent of patients in each group interrupted treatment for reasons unrelated to virologic response. Median change in CD4 count during TI was not significantly different between the nonrebounder and rebounder groups (-20.5/microl vs. -64.0/microl; p < 0.086). In a multivariate logistic regression analysis, the following factors predicted nonrebounder status: peak VL before TI (log10 copies/ml) (OR = 0.14, 95% CI = 0.04-0.48, p = 0.0016); having received HAART (vs. mono/dual therapy) as initial regimen (OR: 11.0, 95% CI: 2.04-59.8, p = 0.0054); and female gender (OR = 4.8, 95% CI = 1.09-21.5, p = 0.0384). The large majority of chronically infected HIV patients with a TI > or = 180 days interrupted treatment for reasons unrelated to virologic response. Almost 30% did not have a significant virologic rebound. Those patients were more likely to be female, had a lower peak VL prior to treatment, and their initial regimen was more likely to be HAART. Examining the immune responses of nonrebounders may contribute to the understanding of protective immunity to HIV. 相似文献
20.
OBJECTIVES: To compare adherence and clinical outcome with highly active antiretroviral therapy (HAART) in intravenous drug users (IDUs) and subjects with other HIV risk behaviours (non-IDUs). METHODS: A total of 133 non-naive HIV-infected patients, 95 (71%) IDUs and 38 (29%) non-IDUs received triple drug therapy with stavudine, lamivudine, and indinavir. Adherence, side effects, and immunological and virological efficacy of treatment were assessed every 3 months. RESULTS: During a median follow-up of 12 months, 43 patients (32% of the total) showed adequate adherence in all clinical appointments. Adherence was superior in non-IDUs than in IDUs in every visit, but a significant difference was found only at 6 months, when 22 (58%) non-IDUs versus 37 (39%) IDUs were adherent (P = 0.047). Mildly increased bilirubin was observed in 69 (52%) patients, and renal colic in 34 (26%). No difference in side effects was found between IDUs and non-IDUs. After 6 months of treatment, 35 (43%) participants presented a CD4 cell count increase >100x10(6)/l, and 47 (58%) achieved undetectable HIV RNA (lower limit of detection: 200 copies/ml). CD4 cell count and HIV RNA responses were similar in both groups. CONCLUSIONS: Adherence to the employed HAART regimen was poor. Non-IDUs were more adherent than IDUs, but the difference between both groups was small. Side effects and efficacy were similar in IDUs and non-IDUs. 相似文献