Cross-sectional comparison of age- and gender-related comorbidities in people living with HIV in Canada.

Because antiretroviral therapy (ART) is allowing people living with human immunodeficiency virus (PLWH) to survive longer, they are developing more age-related comorbidities. We evaluated the effects of age and gender on the burden of age-related comorbidities among PLWH. In this retrospective real-world study, de-identified data were extracted from the medical charts of 2000 HIV-positive adults on ART across 10 sites in Canada. The prevalence of age-related comorbidities was determined in 6 age subgroups (<30, 30-39, 40-49, 50-59, 60-69, and ≥70 years). The effects of gender on these comorbidities were also examined. Risks of cardiovascular disease and chronic kidney disease (CKD) were calculated using the Framingham and D:A:D equations. Most persons were White (68%), male (87%), and virologically suppressed (94%). The mean age was 50.3 years (57% aged ≥50 years), and mean CD4+ T-cell count was 616 cells/mm3. The most common comorbidities were neuropsychiatric symptoms (61%), overweight/obesity (43%), liver disease (37%), and dyslipidemia (37%). The mean number of comorbidities increased across age subgroups (P < .001). Across all age subgroups, the prevalence of hypertension (P = .04), dyslipidemia (P = .04), CKD (P = .03), bone fragility (P = .03), and depression (P = .02) differed between males and females. Both age (P < .001) and gender (P < .001) impacted cardiovascular disease and CKD risk. Age and gender influenced the burden, types, and risks of age-related comorbidities in PLWH in this Canadian cohort. These comorbidities should be diagnosed and treated in routine clinical practice.

Healthcare resource utilization and costs associated with renal, bone and cardiovascular comorbidities among persons living with HIV compared to the general population in Quebec, Canada.

There is limited understanding on healthcare utilization and costs of age-related comorbidities such as cardiovascular, bone and renal disease/disorder in people living with human immunodeficiency virus, so we compared comorbidity prevalence and associated healthcare utilization and costs. Through the Quebec health insurance database, people living with human immunodeficiency virus on antiretroviral therapy for ≥6 months from January 2006 to June 2012 were categorized by their comorbidity status using International Classification of Diseases (ICD)-9 codes, and controls without human immunodeficiency virus diagnosis or antiretroviral therapy use were age and gender matched. We compared healthcare utilization and costs. A total of 3,905 people living with human immunodeficiency virus and 11,715 control individuals were included. The mean age of people living with human immunodeficiency virus was 45.3 years and 77.3% were men. Prevalence of comorbidities was higher and occurred earlier in people living with human immunodeficiency virus and increased with older age regardless of human immunodeficiency virus status. Interestingly, bone comorbidity was high (37%) and 5-fold greater in people living with human immunodeficiency virus <20 years than the controls. Polypharmacy and comorbidity scores were greater in people living with human immunodeficiency virus than controls (p<0.01), as were cardiovascular, bone and renal comorbidities (40.3%, 26.0% and 5.5%, respectively; p<0.01). People living with human immunodeficiency virus had higher healthcare utilization and costs than controls largely due to longer hospital stays and prescriptions. Mean total healthcare cost/person/year for people living with human immunodeficiency virus was CAD$6,248 and was highest for those with renal disease (CAD$19,617). Comorbidities in people living with human immunodeficiency virus are more prevalent, occur earlier and incur a higher burden on the healthcare system; earlier screening and improved preventative and management strategies may reduce the burden to people living with human immunodeficiency virus and to the healthcare system.

DDX17 promotes the production of infectious HIV-1 particles through modulating viral RNA packaging and translation frameshift.

RNA helicases are a large family of proteins that rearrange RNA structures and remodel ribonucleic protein complexes using energy derived from hydrolysis of nucleotide triphosphates. They have been shown to participate in every step of RNA metabolism. In the past decade, an increasing number of helicases were shown to promote or inhibit the replication of different viruses, including human immunodeficiency virus type 1. Among these helicases, the DEAD-box RNA helicase DDX17 was recently reported to modulate HIV-1 RNA stability and export. In this study, we further show that the helicase activity of DDX17 is required for the production of infectious HIV-1 particles. Over expression of the DDX17 mutant DQAD in HEK293 cells reduces the amount of packaged viral genomic RNA and diminishes HIV-1 Gag-Pol frameshift. Altogether, these data demonstrate that DDX17 promotes the production of HIV-1 infectious particles by modulating HIV-1 RNA metabolism.

From promoting to inhibiting: diverse roles of helicases in HIV-1 Replication.

Helicases hydrolyze nucleotide triphosphates (NTPs) and use the energy to modify the structures of nucleic acids. They are key players in every cellular process involving RNA or DNA. Human immunodeficiency virus type 1 (HIV-1) does not encode a helicase, thus it has to exploit cellular helicases in order to efficiently replicate its RNA genome. Indeed, several helicases have been found to specifically associate with HIV-1 and promote viral replication. However, studies have also revealed a couple of helicases that inhibit HIV-1 replication; these findings suggest that HIV-1 can either benefit from the function of cellular helicases or become curtailed by these enzymes. In this review, we focus on what is known about how a specific helicase associates with HIV-1 and how a distinct step of HIV-1 replication is affected. Despite many helicases having demonstrated roles in HIV-1 replication and dozens of other helicase candidates awaiting to be tested, a deeper appreciation of their involvement in the HIV-1 life cycle is hindered by our limited knowledge at the enzymatic and molecular levels regarding how helicases shape the conformation and structure of viral RNA-protein complexes and how these conformational changes are translated into functional outcomes in the context of viral replication.

The transmembrane domain of BST-2 determines its sensitivity to down-modulation by human immunodeficiency virus type 1 Vpu.

Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin) restricts the production of a number of enveloped viruses by blocking virus release from the cell surface. This antiviral activity is counteracted by such viral factors as Vpu of human immunodeficiency virus type 1 (HIV-1). Here, we report that Vpu antagonizes human BST-2 but not BST-2 derived from African green monkeys. The determinants of susceptibility to Vpu map to the transmembrane domain of BST-2. In accordance with this, expression of human BST-2 containing a modified transmembrane domain effectively blocks the replication of wild-type Vpu-expressing HIV-1 in CD4+ T cells. Furthermore, these BST-2 variants, as opposed to wild-type human BST-2, are refractory to Vpu-mediated down-regulation as a result of an attenuated interaction with Vpu. In view of the work by others pointing to a key role of the transmembrane domain of Vpu in promoting virus release, our data suggest that a direct interaction through the transmembrane domain of each of these two proteins is a prerequisite for Vpu to down-modulate BST-2.