Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy

Zhang, Shuangjie; Sighem, Ard van; Kesselring, Anouk; Gras, Luuk; Smit, Colette; Prins, Jan M.; Kauffmann, Robert H.; Richter, Clemens; Wolf, Frank de; Reiss, Peter

doi:10.1097/qai.0b013e318258c651

Cited by 28 publications

(25 citation statements)

References 32 publications

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“…Several studies discussed above suggest the potential for alteration of immune activation and inflammation during periods of LLV. However, a large cohort study found no increased risk of non-AIDS disease associated with LLV compared to that associated with viral suppression, although 75% of LLV episodes consisted of viral blips only (95).…”

Section: Figmentioning

confidence: 95%

“…Two recent studies found no association between LLV (Ͻ400 cpm) and AIDS progression and/or overall mortality (94,95 preted with caution, because any impact on morbidity and mortality is likely to be modest and require a long period of follow-up and a large number of participants in order to be detected. Other investigators have observed a correlation between cumulative plasma HIV-1 exposure over time and both AIDS and non-AIDS morbidity and mortality (96), and they speculated that these effects may be due to the sequelae of increased systemic immune activation and inflammation (82,97).…”

Section: Figmentioning

confidence: 99%

“…Some markers of inflammation and/or endothelial activation have also been studied (91)(92)(93)(94)(95). In the subgroup with a pVL of Ͻ400 cpm in one study, the levels of von Willebrand factor (vWF) remained higher than in the HIV-negative controls and correlated with levels of interleukin-6 (IL-6) (91).…”

Section: Figmentioning

confidence: 99%

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Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

Ryscavage

Kelly

et al. 2014

Antimicrob Agents Chemother

112

101

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A goal of HIV therapy is to sustain suppression of the plasma viral load below the detection limits of clinical assays. However, widely followed treatment guidelines diverge in their interpretation and recommended management of persistent viremia of low magnitude, reflecting the limited evidence base for this common clinical finding. Here, we review the incidence, risk factors, and potential consequences of low-level HIV viremia (LLV; defined in this review as a viremia level of 50 to 500 copies/ml) and verylow-level viremia (VLLV; defined as a viremia level of <50 copies/ml detected by clinical assays that have quantification cutoffs of <50 copies/ml). Using this framework, we discuss practical issues related to the diagnosis and management of patients experiencing persistent LLV and VLLV. Compared to viral suppression at <50 or 40 copies/ml, persistent LLV is associated with increased risk of antiretroviral drug resistance and overt virologic failure. Higher immune activation and HIV transmission may be additional undesirable consequences in this population. It is uncertain whether LLV of <200 copies/ml confers independent risks, as this level of viremia may reflect assay-dependent artifacts or biologically meaningful events during suppression. Resistance genotyping should be considered in patients with persistent LLV when feasible, and treatment should be modified if resistance is detected. There is a dearth of clinical evidence to guide management when genotyping is not feasible. Increased availability of genotypic assays for samples with viral loads of <400 copies/ml is needed.

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Section: Figmentioning

confidence: 95%

Section: Figmentioning

confidence: 99%

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Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

Ryscavage

Kelly

et al. 2014

Antimicrob Agents Chemother

112

101

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“…24 Evidence concerning the effect of low, detectable levels (,200 copies/mL) of HIV viraemia on clinical outcomes is scant. 10,18,23 Our study is the first, to our knowledge, to evaluate the effect of low-level viraemia, measured as VCY-l, on allcause mortality. Our findings show that patients who maintain low-level VCY-l have a risk of death similar to those with suppressed VCY during follow-up.…”

Section: Discussionmentioning

confidence: 99%

Low-level viraemia, measured as viraemia copy-years, as a prognostic factor for medium–long-term all-cause mortality: a MASTER cohort study

Quiros-Roldan

Raffetti

Castelli

et al. 2016

J. Antimicrob. Chemother.

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“…33 Recently in an observational cohort of ART-treated patients, episodes of high-level viremia predicted cardiovascular events. 34 In light of emerging evidence regarding the harm of uncontrolled 29 and from a Danish nationwide population-based cohort (right). 14 …”

Section: Discussionmentioning

confidence: 99%

Incidence and Clinical Features of Cerebrovascular Disease Among HIV-Infected Adults in the Southeastern United States

Vinikoor

Napravnik

Floris-Moore

et al. 2013

AIDS Research and Human Retroviruses

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With aging of the HIV-infected population, non-AIDS conditions such as cardiovascular disease (CVD) now account for substantial mortality and morbidity. While myocardial infarction is the major outcome of interest in the field of HIV and CVD, cerebrovascular disease remains understudied, especially in the Southeastern United States. We determined the incidence and clinical features of cerebrovascular events (CVE) in a large HIV clinical cohort in North Carolina (NC). A total of 2,515 HIV-infected adults contributed a median of 4.5 years (IQR: 2.0, 7.8) of follow-up. Fifty-three CVEs were adjudicated for an incidence rate of 3.87 per 1,000 person-years (95% CI: 2.90, 5.06). The ischemic stroke incidence was 2.26 per 1,000 person-years (95% CI: 1.53, 3.21), approximately 1.5 times the rate of a population-based cohort in NC. At the time of CVE, the median age was 48 years (IQR: 42, 55). Of ischemic strokes 76% resulted from large artery atherosclerosis or small vessel (lacunar) disease. In multivariable analyses, age, hypertension, dyslipidemia, recent CD4 + cell count £ 200 cells/mm 3 , and recent HIV RNA > 400 copies/ml were associated with an increased risk of CVE. Antiretroviral therapy (ART) was not associated with the risk of CVE. We concluded that in the post-ART era, HIV-infected individuals appear to be at moderately increased risk of stroke. Prevention of CVEs in this population will require modification of traditional CVD risk factors and early, effective treatment of HIV infection.

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Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy

Cited by 28 publications

References 32 publications

Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

Low-level viraemia, measured as viraemia copy-years, as a prognostic factor for medium–long-term all-cause mortality: a MASTER cohort study

Incidence and Clinical Features of Cerebrovascular Disease Among HIV-Infected Adults in the Southeastern United States

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