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Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART.
Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who i...
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Citations
... [13] A multi-centre study done in Spain found that the outcome of patients on a long term was associated with immunologic response by the end of one year of therapy and age at the time of HAART initiation, but not with the first antiretroviral combination selected. [14] A study in South Korea showed that fewer new medicines in HAART, advanced clinical stage, and poor adherence to clinic appointment for 1 year after HAART were important risk factors for developing new AIDS-defining illnesses or death. The study concluded that adherence to clinic visits early after starting HAART is an independent predictor of long-term clinical advancement in HIV patients. ...
... This is similar to 5.3% of patients in a study in Spain who developed a new AIDS-defining event while on HAART. [14] This similarity may be due to similarities in HAART regimen which were protease inhibitor-based and non-nucleoside reverse-transcriptase inhibitor-based. Similarly in Taiwan, it was found that HIV-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of HAART or non-adherent to HIV care and HAART, and those in whom non-HIV-related infections have emerged as a significant cause of disease and death in the post-HAART era. ...
Human Immunodeficiency Virus (HIV) attacks the body’s immune system and is responsible for a
major public health problem. Highly Active Anti-Retroviral Therapy (HAART) is key to its management. This study
aimed at evaluating and comparing the clinical and virological outcomes of three HAART regimens - TLD, TLE and
TL/LPV/r. Number of participants was 330 patients (110 in each group). Data were analysed and compared between
groups. A 5-parameter scoring system was used to compare the performance of the regimens. Overall mean age was
44.7 (±10.7) years. Normal BMI 138 (41.8%), overweight (33.3%), obese (20.9%) and underweight (3.9%). Normal
hemoglobin level, 194 (58.8%). Mean baseline CD4 count was 389.9 ± 293.7. Adherence to TLD (90.0%), TLE
(89.1%), TL/LPVr (62.7%). TLD group showed the most clinical improvement with the most patients in stage 1
after one year, 108 (99.1%). Viral suppression at 6 months for TLD (86.4%), TLE (86.4%), TL/LPVr (50.0%) and at
12 months, TLD (90.0%), TLE (91.8%), TL/LPVr (88.2%). The difference in viral suppression between the
TLD/TLE and TL/LPVr groups was statistically significant (p < 0.001). Factors associated with WHO clinical stage
1 at 6 months were age ≥35 years with TLD and female sex for TLE; and with viral suppression at 6 months were
good adherence with TLD and TL/LPVr and female sex with TLE. For all patients collectively, good adherence was
significantly associated with viral suppression at 6 months and 1 year. Predictor of WHO stage 1 at 6 months was
female sex, OR 0.483 (95% CI 0.238 – 0.980). For predictors of viral suppression at 6 months, good adherence had
the highest odds ratio, OR 6.911 (95% CI 3.768 – 12.676), being currently married OR 1.826 (95% CI 1.036 –
3.217). TLD performed best with a score of 14, TLE 13, TL/LPVr 5, out of a maximum score of 15.
... (14) In a multi-centre study done in Spain the commonest causes of death were cancers and liver failure. (15) An Indian study determined that the mean baseline CD4 cell count was 112 ± 60 cells/μL. During follow-up, as many as 80.8% patients showed clinical improvement. ...
Laboratory parameters are used to monitor diseases and treatment processes. Abnormalities in laboratory parameters of HIV patients before commencement of anti-retroviral therapy and their association with patients' treatment outcomes were evaluated. Patients were followed up and data on laboratory investigations and WHO clinical staging of were collected from 330 patients in 2021 and 2022. One hundred and thirty-six (41.2%) were found to be anaemic. Mean baseline CD4 count was 389.9 ± 293.7. The majority had other baseline laboratory parameters within normal range, creatinine 308 (93.3%), ALAT 285 (86.4%) and ASAT 253 (76.7%). Predictor of WHO stage 1 at 6 months was CD4 ≥ 350 cells/mm 3 , OR 1.474 (95% CI 0.096-0.545). Predictor of viral suppression at 6 months was also CD4 ≥ 350 cells/mm 3 , OR 0.994 (95% CI 0.217-0.632).
... 8,[10][11][12][13] Although ART results in a decrease in the hospitalization rate for AIDS-related disease, it increased the risk of many complications related to "non-AIDS" as a cause of death and hospitalization. [17][18][19][20][21] Until now, a comprehensive literature survey has revealed the scarce of information in Saudi Arabia concerning diseases among PLWHIV whose HIV infection is under control and the conditions that lead to deaths. The present research study was therefore designed to examine the prevalence of PLWHIV related AIDS diseases, data profiling levels AIDS-related illness and death among patients treated at PSMMC in Riyadh, Saudi Arabia. ...
Objectives:
To investigate clinical characteristics and the outcome of people living with HIV (PLWHIV) at tertiary care center in Riyadh, Saudi Arabia. Methods: The present retrospective, observational study was carried between 2000-2019 at Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. The demographic and clinical characteristics of 137 PLWHIV patients were collected by reviewing the medical data record. Results: Of the total 137 PLWHIV, 78.8% were male and 21.2% were female. At care entry, the most opportunistic infections found were the cytomegalovirus infections. cytomegalovirus (CMV) infections in 13.8% of patients, tuberculosis (8%), AIDS associated malignancy (10.9%), hepatitis B (5.8%), NTM (3.6%), hepatitis C (2.2%). In the present study, more than half of the patients received integrase based combination therapy. The highest number (n=20) of patients were diagnosed in 2018. Conclusions: Our findings describe the clinical characteristics and outcomes of PLWHIV at a major tertiary referral hospital in Saudi Arabia. The non AIDS related disease is the major cause of death in HIV infected patients. Early diagnosis and initiation of antiretroviral therapy resulted in a significant decrease in morbidity and mortality.
... Антиретровирусная терапия (АРТ) подавляет репликацию ВИЧ, чем способствует росту числа CD4 + Т-лимфоцитов, увеличению про-должительности и улучшению качества жизни больных. Вместе с тем по неизвестной причине у 10-30% ВИЧ-позитивных лиц снижение вирусной нагрузки не приводит к повышению количества CD4 + Т-клеток, что увеличивает риск заболеваемости и смертности пациентов от СПИД-ассоциированных болезней и заболеваний, не ассоциированных со СПИД [4]. Характерным признаком таких субъектов, называемых Активация и IL-7R при ВИЧ-инфекции Activation and IL-7R in HIV-infection 2020, Vol. 23, № 3 2020, Т. 23, № 3 иммунологическими неответчиками на лечение, является высокий уровень хронической иммунной активации, постепенно нарушающей гомеостаз CD4 + Т-лимфоцитов [7]. ...
Approximately 30 % of HIV-infected patients with viral load being suppressed during the course of antiretroviral therapy do not recover their peripheral CD4+T-lymphocyte counts. The reason for this phenomenon, named immunological non-response to treatment, remains unknown. In HIV-positive subjects receiving treatment, interleukin 7 plays a key role in increasing the number and supporting the viability of CD4+T-lymphocytes. We hypothesized that chronic immune activation, which develops in response to immunological failure during the therapy course, may reduce the susceptibility of CD4+T-cells to interleukin 7 in HIV-positive subjects. We examined 38 HIV-infected immunological non-responders to therapy; 42 HIVpositive patients with a standard response to treatment; 19 uninfected volunteers. The content of CD4+, CD4+CD127+ and activated HLA-DR+CD38+T-lymphocytes was determined in the peripheral blood of the examined individuals; the concentration of interleukin 7 was established. As a result, it was shown that interleukin 7 concentrations in the blood plasma of HIV positive immunological non-responders to treatment does not differ from the corresponding values of patients who gave a standard response to antiretroviral therapy. At the same time, immunological non-responders to treatment compared with subjects of both control groups were characterized by a deficiency of absolute and relative CD4+CD127+T-cell counts capable of responding to interleukin 7. Moreover, the interleukin 7 receptor expression level was reduced on CD4+T-lymphocytes of immunological non-responders. The higher was the frequency of activated CD4+T-lymphocytes; the lower was the CD127+ expression density. It should be noted that after excluding the data obtained from patients coinfected with HIV and hepatitis C virus, which are known to have significantly higher levels of chronic immune activation and systemic inflammation, we found no differences in CD127 expression between HIVpositive patients with distinct effectiveness of the immunological response to treatment. Thus, in the present study, we showed that in HIV-infection, poor immunologic response to antiretroviral therapy is associated with a decrease in the CD4+CD127+T-cell counts. Moreover, an increase in the level of chronic immune activation is associated with a decrease in CD127 expression density on CD4+T-lymphocytes.
... older age, low CD4 nadir, long duration of HIV infection) but none of these factors provides a full explanation for the lack of immune reconstitution [4]. Additionally, INR have been associated with an increased risk of AIDS and serious non-AIDS events as well as mortality [5][6][7]. For these reasons, substantial efforts are being pursued to improve the identification and management of this key population [7][8][9][10]. ...
Objectives
Immune non-responders (INR) have poor CD4 recovery and are associated with increased risk of serious events despite antiretroviral therapy (ART). A clinically relevant definition for INR is lacking.Methods
We conducted a retrospective analysis of three large cohorts: Infectious Disease Clinic at the Atlanta Veterans Affairs Medical Center, the US Military HIV Natural History Study and Infectious Disease Program of the Grady Health System in Atlanta, Georgia. Two-stage modeling and joint model (JM) approaches were used to evaluate the association between CD4 (or CD4/CD8 ratio) slope within two years since ART initiation and a composite endpoint (AIDS, serious non-AIDS events and death) after two years of ART. We compared the predictive capacity of four CD4 count metrics (estimated CD4 slope, estimated CD4/CD8 ratio slope during two years following ART initiation and CD4 at 1 and 2 years following ART initiation) using Cox regression models.ResultsWe included 2,422 patients. Mean CD4 slope (±standard error) during two years of ART was 102 ± 2 cells/μl/year (95% confidence interval: 98-106 cells/μl/year), this increase was uniform among the three cohorts (p = 0.80). There were 267 composite events after two years on ART. Using the JM approach, a CD4 slope ≥100 cells/μL/year or CD4/CD8 ratio slope >0.1 higher rate per year were associated with lower composite endpoint rates (adjusted hazard ratio [HR] = 0.80, p = 0.04 and HR = 0.75 p
... In the late cART era, hospitalization rates have decreased, mostly due to a decrease in the rate of AIDS-related illnesses. Consequently, non-AIDS related illnesses have become more common as the cause of mortality and hospitalization [5][6][7][8]. This shift in the cause of death and hospitalization is associated with the widespread use of combined antiretroviral therapy (cART) and better care in developed settings [9][10][11]. ...
Background
Acquired ImmunoDeficiency Syndrome (AIDS) related illnesses are the leading cause of death in the developing world. However; there is limited evidence regarding the incidence of mortality among admitted HIV patients in Ethiopia.
Objective
To determine the incidence of mortality and its predictors among admitted HIV/AIDS patients in selected tertiary care hospitals in Ethiopia.
Methods
A prospective cohort study involving 136 admitted HIV/AIDS patients from April 1 to August 31, 2018 was conducted in selected tertiary care hospitals in Ethiopia. Data were collected on socio-demographic, clinical characteristics, and drug related variables. Kaplan-Meier and Cox regression were used to compare survival experience of the patients and identify independent predictors of mortality. Hazard ratio was used as a measure of strength of association and p-value of <0.05 was considered to declare statistical significance.
Results
Of 136 patients, 80 (58.8%) were females. The overall in-hospital incidence of mortality was 2.83 per 1000 person-years. The incidences of mortality due to AIDS and non-AIDS related admissions were 6.1 [3.95, 8.67] and 5.3 [3.35, 8.23] per 1000 person-years respectively. The mean ± SD survival times among patients with AIDS and non-AIDS related illnesses were 32 ± 3.1 and 34 ± 3.3 days respectively (log rank p = 0.599). Being on non-invasive ventilation (AHR: 2.99, 95%CI; [1.24, 7.28]; p = 0.015) and having baseline body mass index (BMI) of less than 18.5 (AHR: 2.6, 95%CI; [1.03, 6.45]; p = 0.04) were independent predictors of mortality.
Conclusion
The study found high incidence of in-hospital mortality among admitted HIV/AIDS patients in Ethiopian tertiary care hospitals. Being on non-invasive ventilation and body mass index (BMI) of less than 18.5 were found to be independent predictors of mortality.
... 4 Suppression of viral replication is the key goal of ART 5 because it allows immune reconstitution, 6 maintains or improves CD4 + levels, 7 prevents HIV transmission, 2,8 decreases the risk of selecting drug-resistant mutations, 9 and reduces HIV-related morbidity and mortality. [10][11][12][13] Early virological response to ART, commonly assessed by HIV viral load (VL) counts 6 months after treatment initiation, is of particular interest because it has proven to be of important prognostic value both in the short and long term for AIDS [14][15][16][17] and allcause mortality. 11,[15][16][17] Virological failure may result from insufficient adherence, presence of pre-treatment HIV drug resistance, issues related to drug absorption or pharmaceutical interactions, or any combination of these factors. ...
Objective:
To identify clinical, sociodemographic, and treatment-related factors associated with early virological response in HIV-infected adults starting antiretroviral treatment (ART) in Brazil in 2014-2015.
Methods:
Data from 4 information systems from the Brazilian AIDS Program were combined to create a historical cohort. Unconditional logistic regression models were used to assess the likelihood of not achieving viral load suppression (VLS), defined as having either a viral load (VL) count >200 copies per milliliter or an aids-related death recorded within 180 ± 90 days after treatment initiation.
Results:
Among 76,950 individuals, 64.8% were men; median age, CD4, and VL counts were 34 years, 378 cells per micro liter, and 38,131 copies per milliliter, respectively, and 85.2% achieved VLS. In the multivariate analysis, some factors which increased the odds of non-VLS were as follows: lower CD4 and higher VL counts, younger age, heterosexual or injection drug use groups (relative to men who have sex with men), lower educational level, black/brown race, higher pill burden, and higher dosing frequency. Regimens containing boosted protease inhibitors were similar to those containing nonnucleoside reverse transcriptase inhibitors and superior to those containing unboosted protease inhibitors (all P values <0.001). No difference was observed between patients with CD4 counts 350-499 and 500+ cells per micro liter.
Conclusions:
Our findings support the decision made in Brazil in 2013 to recommend immediate initiation of ART regardless of clinical stage or CD4. Several factors were found to be associated with poorer virologic outcomes and should be addressed to maximize ART adherence and success rates.
... [19,22,23] The relative CD4 recovery of nPHIV youth living with HIV is unclear; studies that have attempted to evaluate the question have tended to lump youth into older age groups or mixed nPHIV youth with perinatally HIV-infected youth, impairing assessment of the specific responses of nPHIV youth to cART. [21,24] [40] [41,42] It is well established that the lower the CD4 at initiation of therapy, the lower CD4 threshold that one will be able to reach, as evidenced by the longitudinal data in this study. [38,43] Individuals with the lowest baseline CD4 values ( 200 cells/mm 3 ), compared to those in the higher CD4 categories, had more rapid rises in CD4 counts (i.e., higher linear slope), but ultimately had lower CD4 levels at the end of follow-up. ...
Background
Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13–24 years-old) and adults (≥25–44 years-old).
Methods
Retrospective analysis of ART-naïve nPHIV individuals 13–44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13–24, 25–34, 35–44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4).
Results
Among 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92–249). Baseline CD4 was higher for youth (320 cells/mm³) than for ages 25–34 (293) or 35–44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm³, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm³, individuals with baseline CD4 of 201–500 and >500 cells/mm³ had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes.
Conclusions
Despite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.
... While the initial goal of these programs was to initiate large numbers of patients on ART and, subsequently, reduce overall morbidity and mortality, the continuing aim is to maintain patients on high quality life-long care. Many studies have examined short-and medium-term outcomes in adult patients enrolled in ART programs across the globe, but there are relatively limited data on the long-term outcomes for large-scale ART programs [2][3][4][5][6][7][8][9][10][11][12]. ...
Background
While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria.
Methods
We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted.
Results
Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm³ (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients retained through 84 months maintained ≥95% adherence.
Conclusion
While improved access to HIV care and treatment remains a challenge in Nigeria, our study shows that a high quality of care was achieved as evidenced by strong long-term clinical, immunologic and virologic outcomes.
... The cART in HIV-infected individuals usually reduces the plasma HIV-RNA to undetectable levels, restores CD4+ T-cell levels and preserves immunologic function [4,5]. However, there is substantial variability in the rate and extent of CD4+ T-cell recovery after starting cART [6]. A significant percentage of cART-treated patients fail to achieve substantial increases in CD4+ T-cell count, and it may contribute to increase the risk of both acquired immune deficiency syndrome (AIDS) and non-AIDS morbidity and mortality [7][8][9]. ...
Background:
The IL7RA polymorphisms have recently been associated associated with CD4+ T-cell decline in untreated HIV-infected subjects, and CD4+ T-cell recovery in patients on combination antiretroviral therapy (cART). The aim of this study was to evaluate whether IL7RA polymorphisms are associated with CD4+ T cell recovery in HIV-infected patients on long-term cART.
Study design:
We performed a retrospective study in 151 naïve cART patients with severe immunodeficiency (CD4+ counts ≤200 cells/mm(3) ). IL7RA polymorphisms genotyping was performed by using Sequenom's MassARRAY platform. The outcome variable was the time to achieve the first value of CD4+ count ≥500 cells/mm(3) during the follow-up.
Results:
Two different trends of CD4+ T cell recovery were found in Kaplan-Meier analysis. During the first 48 months, 60/151 (39.7%) of the patients reached CD4+ T cell values ≥500 cells/mm(3) , and no differences were observed between IL7RA genotypes. After the first 48 months of follow-up, 27/151 (17.8%) of the patients reached CD4+ T cell values ≥500 cells/mm(3) , with a different pattern of CD4+ recovery depending on IL7RA genotype. Patients with rs10491434 TT genotype and rs6897932 TT genotype were more likely of achieving CD4+ value ≥500 cells/mm(3) than patients with rs10491434 CT/CC genotype (adjusted hazard ratio (aHR)=3.59; p=0.005) and patients with rs6897932 CC/CT genotype (aHR=11.7; p<0.001).
Conclusions:
The IL7RA polymorphisms seem to be associated with CD4+ T cell recovery in HIV-infected patients who started cART with severe immunodeficiency, in the second phase of CD4+ T cell recovery after long-term cART. This article is protected by copyright. All rights reserved.
