A recent article in the journal Addiction compares clinical outcomes for HIV patients infected via injection drug use (IDU) or sexual transmission (ST). The authors compare outcomes for over a thousand IDU patients to nearly 9000 ST patients in Spain. Perhaps not surprisingly the IDU patients have greater risks in every metric evaluated. 16Garcia
To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS.
Prospective multi-centre cohort study of HIV-infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS).
Thirty-one centres from the Spanish public health-care system.
A total of 9355 patients were included (1064 HIV-IDU and 8291 HIV-ST) during 2004-13.
We compared LP (defined as presentation for care with a CD4 cell count < 350/μl and/or AIDS-defining illness), delayed ART initiation (defined as initiating treatment more than 6 months after the date when treatment was indicated by the guidelines, or not initiating treatment at all when it was indicated), virological and immunological response to ART (defined as viral load < 50 HIV-1 RNA copies/ml and a CD4 count increase of at least 100 cells/μl, respectively, after 1 year of treatment), mortality and progression to AIDS in HIV-IDU and HIV-ST.
Compared with HIV-ST, HIV-IDU had higher risk of LP [odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.41-2.18], delayed ART initiation (OR 1.87; 95% CI = 1.46-2.40) and higher mortality [hazard ratio (HR) = 1.43; 95% CI = 1.03-2.01] and risk of progression to AIDS [subhazard ratio (SHR) = 1.68; 95% CI = 1.29-2.18]. Virological suppression due to ART was lower in HIV-IDU than in patients with HIV-ST only among patients without hepatitis C virus (HCV) infection [adjusted OR (aOR) = 0.59; 95% CI = 0.36-0.95]; among patients with HCV infection, virological suppression due to ART did not show significant differences between HIV-IDU and HIV-ST. There were no significant differences in immunological response after adjusting by HCV (aOR = 0.74; 95% CI = 0.52-1.06).
In Spain, patients who acquire HIV infection through use of injected drugs appear to have a higher risk of late presentation, delayed initiation of anti-retroviral treatment and progression to AIDS and death than patients who acquire HIV by sexual transmission.
Protease inhibitors are a widely used anti-retroviral therapy, but they do have some significant side effects. Patient compliance with a drug regimen declines when they experience side effects. Several therapies to counteract the protease inhibitor effects on fat metabolism have been attempted with limited results.
In this recent study (16Dasuri) the authors evaluate the effects of adiponectin on metabolism in mice treated with protease inhibitors. It should be noted that mice aren’t always the best models for neuro-cognitive disorders (for example, there’s no good mouse model for Alzheimer’s or ASD). However, this is a very interesting study.
HIV protease inhibitors are key components of HIV antiretroviral therapies, which are fundamental in the treatment of HIV infection. However, the protease inhibitors are well-known to induce metabolic dysfunction which can in turn escalate the complications of HIV, including HIV associated neurocognitive disorders. As experimental and epidemiological data support a therapeutic role for adiponectin in both metabolic and neurologic homeostasis, this study was designed to determine if increased adiponectin could prevent the detrimental effects of protease inhibitors in mice. Adult male wild type (WT) and adiponectin-overexpressing (ADTg) mice were thus subjected to a 4-week regimen of lopinavir/ritonavir, followed by comprehensive metabolic, neurobehavioral, and neurochemical analyses. Data show that lopinavir/ritonavir-induced lipodystrophy, hypoadiponectinemia, hyperglycemia, hyperinsulinemia, and hypertriglyceridemia were attenuated in ADTg mice. Furthermore, cognitive function and blood–brain barrier integrity were preserved, while loss of cerebrovascular markers and white matter injury were prevented in ADTg mice. Finally, lopinavir/ritonavir caused significant increases in expression of markers of brain inflammation and decreases in synaptic markers in WT, but not in ADTg mice. Collectively, these data reinforce the pathophysiologic link from metabolic dysfunction to loss of cerebrovascular and cognitive homeostasis; and suggest that preservation and/or replacement of adiponectin could prevent these key aspects of HIV protease inhibitor-induced toxicity in clinical settings.
The Retrovirology Journal Club will continue through the summer and fall semesters. Science never stops!
Journal club is the first and third Wednesday of the month at 5:00 pm. Rooms are:
6/15/16 BRT 105
10/19/16 No journal club
12/21/16 No journal club