CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: A Longitudinal Cohort Study from COHERE

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doi:10.1371/journal.pmed.1001194

Cited by 145 publications

(74 citation statements)

References 40 publications

(57 reference statements)

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“…The declining CD4 cell count influences both the frequency and severity of active TB disease [20], and active TB disease may be associated with a higher HIV viral load and more rapid progression of HIV disease [21]. Such cases presenting for TB treatment with advanced HIV infection are also likely to present with other AIDS-defining diseases which further add to the risk of dying [22]. …”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

Takarinda

Sandy

Masuka

et al. 2017

Tuberculosis Research and Treatment

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Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46–282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35–4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10–1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44–2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22–0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART.

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Section: Discussionmentioning

confidence: 99%

Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

Takarinda

Sandy

Masuka

et al. 2017

Tuberculosis Research and Treatment

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“…Indeed, AIDS-related events are still the leading cause of early mortality among persons living with HIV on cART in low- and middle-income settings, even among those with virologic suppression 15,33 . Consequently, current treatment guidelines offer no provision for patients who start cART but who will ultimately clinically progress.…”

Section: Discussionmentioning

confidence: 99%

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case–Cohort Study

Balagopal

Asmuth

Yang

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

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“…Persistently low CD4+ T cell counts despite ART has been consistently associated with an increased risk for combined non-AIDS morbidity and mortality in several large cohort studies and clinical trials in North America and Europe (Achhra et al, 2010; Baker et al, 2008; Marin et al, 2009; Mocroft et al, 2010; Smurzynski et al, 2010). Interestingly, there continues to be an incremental decrease in mortality risk with increasing CD4+ T cell counts even among those with CD4+ T cell counts >500 cells/mm 3 , suggesting that continued CD4+ T cell recovery—even after recovering “normal” levels—may continue to confer clinical benefit (Young et al, 2012). Several studies have also linked persistent CD4+ T cell lymphopenia to an increased risk of specific non-AIDS morbidities including cardiovascular disease (Lichtenstein et al, 2010; Triant et al, 2010), osteoporosis, and fracture risk (Yong, Elliott, Woolley, & Hoy, 2011).…”

Section: Persistent Cd41+ T Cell Lymphopenia Predicts Clinical Outmentioning

confidence: 99%

Residual Immune Dysregulation Syndrome in Treated HIV infection

Lederman

Funderburg

Sékaly

et al. 2013

Advances in Immunology

303

273

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Antiretroviral therapy has revolutionized the course of HIV infection, improving immune function and decreasing dramatically the mortality and morbidity due to the opportunistic complications of the disease. Nonetheless, even with sustained suppression of HIV replication, many HIV-infected persons experience a syndrome characterized by increased T cell activation and evidence of heightened inflammation and coagulation. This residual immune dysregulation syndrome or RIDS is more common in persons who fail to increase circulating CD4+ T cells to normal levels and in several epidemiologic studies it has been associated with increased morbidity and mortality. These morbid and fatal events are not the typical opportunistic infections and malignancies seen in the early AIDS era but rather comprise a spectrum of cardiovascular events, liver disease, metabolic disorders, kidney disease, bone disease, and a spectrum of malignant complications distinguishable from the opportunistic malignancies that characterized the earlier days of the AIDS epidemic. While immune activation, inflammation, and coagulopathy are characteristic of untreated HIV infection and improve with drug-induced control of HIV replication, the drivers of RIDS in treated HIV infection are incompletely understood. And while inflammation, immune activation, and coagulopathy are more common in treated persons who fail to restore circulating CD4+ T cells, it is not entirely clear how these two phenomena are linked.

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CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: A Longitudinal Cohort Study from COHERE

Abstract: Using data from the Collaboration of Observational HIV Epidemiological Research Europe, Jim Young and colleagues show that in successfully treated patients the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression.

Cited by 145 publications

References 40 publications

Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case–Cohort Study

Residual Immune Dysregulation Syndrome in Treated HIV infection

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