A CD4+ Cell Count &lt;200 Cells per Cubic Millimeter at 2 Years After Initiation of Combination Antiretroviral Therapy Is Associated With Increased Mortality in HIV-Infected Individuals With Viral Suppression

Loutfy, Mona; Genebat, Miguel; Moore, David; Raboud, Janet; Chan, Keith; Antoniou, Tony; Milan, David J.; Shen, Anya; Klein, Marina B.; Cooper, Curtis; Machouf, Nimâ; Rourke, Sean B.; Rachlis, Anita; Tsoukas, Chris; Montaner, Julio S. G.; Walmsley, Sharon; Śmieja, Marek; Bayoumi, Ahmed M.; Mills, Edward J.; Hogg, Robert S.

doi:10.1097/qai.0b013e3181ec28ff

Cited by 45 publications

(44 citation statements)

References 41 publications

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“…Others argue that patients starting treatment with low counts do not seem to remain disadvantaged if the CD4 cell count at the start of treatment is not predictive of survival once adjusted for a value at 6 mo [4]. We see our results—with a higher CD4 cell count becoming even more important over time for patients with low CD4 cell counts—as more consistent with the idea of lasting damage below some threshold from which recovery is difficult [18],[36]. Many patients starting therapy with a CD4 cell count below 200 cells/µl never achieve a normal CD4 cell count even after 10 y of otherwise effective antiretroviral therapy [37], although this failure to recover could be due to factors other than a low CD4 cell count per se.…”

Section: Discussionsupporting

confidence: 81%

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

2012

PLoS Med

141

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Section: Discussionsupporting

confidence: 81%

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

2012

PLoS Med

141

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“…While these findings provide important insights into the mechanisms determining the immunological response to ART, they still fail to formally prove that the level of microbial translocation is a key factor regulating CD4 ϩ T-cell reconstitution upon virologically suppressive ART. Given the well-described increased risk of AIDS-and non-AIDS-related morbidity and mortality in HIVinfected patients who do not experience full immunological recovery on ART (113,114), further ad hoc-designed observational and randomized studies are warranted to investigate this crucial aspect of SIV/HIV pathogenesis.…”

Section: Clinical Implications Of Microbial Translocation In Hiv Disementioning

confidence: 99%

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

2013

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SUMMARYIn pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species.In vivostudies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4+depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Directin situevidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS.

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“…Virologic suppression was defined as per DHHS guidelines 9 where non-sustained increases in VL were not considered evidence of unsuppressed VL. A value of 200 cells/mm 3 for CD4 counts was chosen because the CDC definition for stage 3 HIV infection (AIDS) was based on this threshold 10 , and because of its association with disease progression 11 and increased mortality 12,13 . A gap in treatment was defined to be three months or more to ensure administrative phenomena resulting from non-uniform prescription refill data were not counted as gaps, and since results from structured treatment interruption trials showed gaps in treatment of 3 months or less had no significant impact on future clinical outcomes 14 .…”

Section: Methodsmentioning

confidence: 99%

A Multi-State Model Examining Patterns of Transitioning Among States of Engagement in Care in HIV-Positive Individuals Initiating Combination Antiretroviral Therapy

Gillis

Loutfy

Bayoumi

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Common measures of engagement in care fail to acknowledge that infrequent follow-up may occur either intentionally among patients with sustained virologic suppression or unintentionally among patients with poor clinical outcomes. Methods Five states of HIV care were defined within the Canadian Observational Cohort (CANOC) Collaboration following combination antiretroviral therapy (cART) initiation: (1) guidelines HIV care (suppressed viral load (VL) and CD4 >200 cells/mm3, no gaps in cART >3 months, no gaps in CD4 or VL measurement >6 months), (2) successful care with decreased frequency of follow-up (as above except no gaps in CD4 or VL measurement >12 months), (3) suboptimal care (unsuppressed VL, CD4<200 cells/mm3 on 2 consecutive visits, ≥1 gap in cART >3 months, or ≥1 gap in CD4 or VL measurement >12 months), (4) loss to follow-up (no contact for 18 months), and (5) death. Multi-state models were used to determine factors associated with transitioning among states. Results 7810 participants were included. Younger age, female gender, Indigenous ethnicity and people who have injected drugs (PWID) were associated with increased likelihoods of transitioning from guidelines to suboptimal care and decreased likelihoods of transitioning from suboptimal to guidelines care. One-fifth of individuals in successful, decreased follow-up after cART initiation (mean sojourn time 0.72 years) were in suboptimal care in subsequent years. Conclusions Using routinely collected data, we have developed a flexible framework that characterizes patient transitions among states of HIV clinical care. We have demonstrated that multi-state models provide a useful approach to supplement ‘cascade of care’ work.

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A CD4+ Cell Count <200 Cells per Cubic Millimeter at 2 Years After Initiation of Combination Antiretroviral Therapy Is Associated With Increased Mortality in HIV-Infected Individuals With Viral Suppression

Abstract: Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.

Cited by 45 publications

References 41 publications

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

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

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

A Multi-State Model Examining Patterns of Transitioning Among States of Engagement in Care in HIV-Positive Individuals Initiating Combination Antiretroviral Therapy

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