Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course (original) (raw)
Related papers
The Journal of antimicrobial chemotherapy, 2015
The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART. This study included naive patients from the PISCIS Cohort with CD4 <200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged >18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders. 2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease prog...
Aids Research and Therapy, 2009
Background Many HIV-infected patients only access health care once they have developed advanced symptomatic disease resulting from AIDS Defining Conditions (ADCs). We carried out a study to establish the effect of ADCs on immunological recovery among patients initiated on antiretroviral therapy (ART). Methods A retrospective cohort of 427 HIV-1 patients who were initiated on ART between January 2002 and December 2006 was studied. Data on ADCs was retrieved from Joint Clinical Research Centre (JCRC) data base and backed up by chart reviews. We employed Kaplan-Meier survival curves to estimate median time to 50 CD4 cells/μl from the baseline value to indicate a good immunological recovery process. Cox proportional hazard models were used at multivariate analysis. Results The median time to gaining 50 CD4 cells/μl from the baseline value after ART initiation was longer in the ADC (9.3 months) compared to the non-ADC group (6.9 months) (log rank test, p = 0.027). At multivariate analysis after adjusting for age, sex, baseline CD4 count, baseline HIV viral load, total lymphocyte count and adherence level, factors that shortened the median time to immunological recovery after ART initiation were belonging to the non-ADC group (HR = 1.31; 95% CI: 1.03–1.28, p = 0.028), adherence to ART of ≥ 95% (HR = 2.22; 95% CI: 1.57–3.15, p = 0.001) and a total lymphocyte count ≥ 1200 cells/mm3 (HR = 1.84; 95% CI: 1.22–2.78, p = 0.003). A low baseline CD4 count of ≤ 200 cells/μl (HR = 0.52; 95% CI: 0.37–0.77, p = 0.001) was associated with a longer time to immunological recovery. There was no interaction between low CD4 counts and ADC group. Conclusion Patients with ADCs take longer to regain their CD4 counts due to the defect in the immune system. This may prolong their risk of morbidity and mortality.
PloS one, 2011
Background: A small but significant number of patients do not achieve CD4 T-cell counts .500cells/ml despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods: Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count ,500cells/ml, HIV RNA,500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts .500cells/ml and .200cells/ml. Results: 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32-47) years and 236 (130-350) cells/ml, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3-10) years. Most patients (80%) achieved CD4 T-cell counts .500cells/ml, but in 8%, this took .5 years. Among the patients who failed to reach a CD4 T-cell count .500cells/ml, 16% received cART for .10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count .500cells/ml was associated with higher baseline CD4 T-cell counts (p,0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts .200cells/ml included higher baseline CD4 T-cell count (p,0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p,0.001). Conclusion: The time taken to achieve a CD4 T-cell count .500cells/ml despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count .500cells/ml.
Journal of Acquired Immune Deficiency Syndromes, 2010
Objective: To determine the long-term impact of immunologic discordance (viral load ,50 copies/mL and CD4 + count #200 cells/mm 3) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART). Methods: Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression. Results: Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4 + count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log 10 copies/mL = 0.46; 95% CI: 0.33 to 0.65). Conclusions: Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.
The Journal of Infectious Diseases, 2011
Background. A subgroup of human immunodeficiency virus type 1 (HIV-1)-infected patients with severe immunodeficiency show persistently low CD41 cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. Methods. Data analysis from a large multicenter cohort incorporating 14,433 HIV-1-infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD41 cell counts ,200 cells/lL who achieved complete and sustained viral suppression ,50 copies/mL (n 5 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD41 cell count >200 cells/lL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. Results. During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82-90.82; and immune responder group, 24.54; 95% CI, 10.59-48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14-0.92; P 5 .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09-8.82; P 5 .03). Conclusion. Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression.
The Journal of Infectious Diseases, 2007
Background. We sought to determine the safety of treatment interruption (TI) and to identify parameters that would define patients with human immunodeficiency virus (HIV) for whom TI is safer. Methods. AIDS Clinical Trials Group 5170 was a multicenter, 96-week-long, prospective study of HIV-infected patients receiving antiretroviral therapy (ART) who had CD4 + cell counts 1350 cells/mm 3 and who underwent TI. Results. A total of 167 patients were enrolled. The median nadir in CD4 + cell count was 436 cells/mm 3. The initial decrease (i.e., during the first 8 weeks) in CD4 + cell count after ART interruption was 20 cells/mm 3 /week; the subsequent decrease was 2.0 cells/mm 3 /week until week 96. Both the CD4 + cell count before enrollment and the increase in CD4 + cell count during ART predicted early decrease; later decrease was predicted by the level of interleukin-7 at enrollment. A Centers for Disease Control and Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2 patients, respectively (all had CD4 + cell counts 1350 cells/mm 3). At week 96, 17 patients had CD4 + cell counts р250 cells/mm 3 , and 46 patients had resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency syndrome). In a multivariate analysis, a higher nadir in CD4 + cell count (1400 cells/mm 3), a lower HIV load (!50 copies/mL) at the time of TI, and an HIV load р22,000 copies/mL before ART predicted a longer time to the primary end point (CDC category B or C event, death, CD4 + cell count р250 cells/mm 3 , or resumption of ART). Conclusion. Disease progression after TI was low in this cohort. A higher nadir in CD4 + cell count, a lower HIV load before ART, and an HIV load р50 copies/mL at the time of TI predicted a longer time to the primary end point. Combination antiretroviral therapy (ART) has prolonged survival and has decreased morbidity due to AIDS [1-3]. Initial guidelines recommended ART for patients with preserved immune function [4, 5]. The inability of ART to eradicate HIV infection and the growing recognition of ART toxicity subsequently led to changes in treatment guidelines; a more conservative approach was embraced, with ART being delayed until
AIDS, 2020
Objectives: Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection. Design: Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection. Methods: We compared regimens based on protease-inhibitors (N ¼ 28), integrasestrand-transfer-inhibitors (InSTI, N ¼ 87) and nonnucleoside-reverse-transcriptase-inhibitors (N ¼ 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 þ T-cell count >900 cells/ml and CD4 þ /CD8 þ ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared. Results: Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in all ART regimens and, InSTI group, comparable for dolutegravir and elvitegravir within InSTIs. CD4 þ T-cell counts at 1 year were comparable in all ART regimens. Overall proportion of patients reaching CD4 þ cell count more than 900 cells/ml and CD4 þ /CD8 þ ratio more than 1 was 36% and 40% and 46% and 63% at 1 and 3 years, respectively with no differences among ART regimens. Starting ART during the earliest Fiebig stages (I-V vs. VI) was associated with higher rates of CD4 þ cell count more than 900 cells/ml at 3 years (P ¼ 0.027). Discontinuation due to adverse events was more frequent with nonnucleoside-reversetranscriptase-inhibitors compared with other ART classes.
The Open AIDS Journal, 2008
Objective: Rates of AIDS defining event (ADE), serious ADE and death by CD4 and HIV RNA categories before and after combination antiretroviral therapy (cART) initiation are lacking for high CD4 counts. Methods: Event rates were estimated within CD4 cell strata using a Poisson regression model adjusting for sex, exposure category, age, and current HIV RNA (<4, 4-4.99, 5 log copies/ml), and including an interaction term between the CD4 cell count and cART indicator. Results : 7317 and 6376 persons contributed to "naïve " and "cART " groups respectively, of whom 3911 contributed to both. At the same CD4 level, the risk of ADE was nearly 2 fold higher during naive follow-up compared to cART for CD4 <500 cells/mm 3. However, after adjustment for current HIV RNA, the risk of ADE became similar for both groups except for CD4 count <200 cells/mm 3 when it is 35% (6-72%) higher for naives. The same results were observed for the risk of serious ADE. There was no evidence of a difference in risk of death between naive and cART follow-up at specific CD4 categories even after adjustment for HIV RNA. Conclusion: Within CD4 cell strata above 200 cells/mm 3 , the risk of ADE before ART initiation is higher than it is following cART initiation.