Search

Objective: Studies focusing on HIV-hepatitis C virus (HCV) coinfected individuals without a history of IDU are limited. It is plausible that poorer clinical outcomes in HIV-HCV coinfection are due to factors associated with IDU, not from HCV itself. This study compares HIV treatment outcomes and survival between HIV-HCV coinfected individuals with and without IDU history., Design: Observational cohort study., Methods: We analyzed data from a multisite Canadian cohort study of HIV-positive individuals initiating combination antiretroviral therapy (ART) after 1 January 2000. This analysis was restricted to 1254 participants with HCV coinfection and known IDU history. Cox proportional hazards regression was used to evaluate time from ART initiation to virologic suppression (two consecutive measures <250 copies/ml) and CD4 cell count recovery (+100 cells/μl). In order to account for loss to follow-up (LTFU), competing risk analysis was used to evaluate time to death., Results: A total of 1254 participants (31% women) were included. During a median follow-up time of 3.8 years (interquartile range = 2.1-6.2), 217 deaths were reported and 148 participants were LTFU. In adjusted multivariable analysis, individuals with IDU history were significantly less likely to achieve virologic suppression [adjusted hazard ratio (AHR) = 0.78, 95% confidence interval (CI) = 0.64-0.95]; marginally less likely to have CD4 cell count recovery (AHR = 0.82, 95% CI = 0.66-1.00); and had a significantly higher risk of death (AHR = 2.15, 95% CI = 1.25-3.70)., Conclusion: IDU history independently elevates risk for poorer clinical outcomes, separate from HCV coinfection. HIV-HCV coinfected persons are not homogeneous in characteristics or outcomes, suggesting care should be taken during statistical analyses if attributing poorer HIV-specific outcomes solely to HCV coinfection.

Objective(s): We investigated the probability of transitioning in or out of the CD3⁺ T-cell homeostatic range during antiretroviral therapy, and we assessed the clinical impact of lost T-cell homeostasis (TCH) on AIDS-defining illnesses (ADIs) or death., Design: Within the Canadian Observational Cohort (CANOC), we studied 4463 antiretroviral therapy (ART)-naive HIV-positive patients initiating combination ART (cART) between 2000 and 2010., Methods: CD3⁺ trajectories were estimated using a four state Markov model. CD3⁺ T-cel percentage states were classified as follows: very low (<50%), low (50-64%), normal (65-85%), and high (>85%). Covariates associated with transitioning between states were examined. The association between CD3⁺ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models., Results: A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3⁺ T-cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4⁺ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3⁺ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27-2.89) and hazard ratio=1.49 (95% CI: 1.13-1.96), respectively]., Conclusion: Patients with very low or high CD3⁺ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART-treated HIV-positive patients.

Objective: Malaria and HIV-1 adversely interact, with HIV-positive individuals suffering higher parasite burdens and worse clinical outcomes. However, the mechanisms underlying these disease interactions are unclear. We hypothesized that HIV coinfection impairs the innate immune response to malaria, and that combination antiretroviral therapy (cART) may restore this response. Our aim was to examine the innate inflammatory response of natural killer (NK), natural killer T (NKT), and γδ T-cells isolated from the peripheral blood of HIV-infected therapy-naive donors to malaria parasites, and determine the effect of cART on these responses., Methods: Freshly isolated peripheral blood mononuclear cells from 25 HIV-infected individuals pre-cART (month 0) and post-cART (months 3 and 6), and HIV-negative individuals at matched time-points, were cultured in the presence of Plasmodium falciparum parasitized erythrocytes. Supernatants and cells were collected to assess cytokine production and phenotypic changes., Results: Compared to HIV-negative participants, NKT, NK, and γδ T-cell subsets from participants with chronic HIV infection showed marked differences, including decreased production of interferon γ (IFNγ) and tumor necrosis factor (TNF) in response to malaria parasites. IFNγ production was linked to interleukin-18 receptor (IL-18R) expression in all three cell types studied. Six months of cART provided partial cellular reconstitution but had no effect on IL-18R expression, or IFNγ and TNF production., Conclusion: These data suggest that HIV infection impairs the inflammatory response of innate effector cells to malaria, and that the response is not fully restored within 6 months of cART. This may contribute to higher parasite burdens and ineffective immune responses, and have implications for vaccination initiatives in coinfected individuals.

Background: Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART., Objective: We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut)., Methods: Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400  mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4(+) T cells carrying HIV-1 proviral DNA was determined., Results: Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4(+) T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4(+) T-cell counts., Conclusion: In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4(+) T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4(+) T-cell counts.

Objective: To evaluate the safety and efficacy of polyalkylimide gel (PAIG) in the treatment of HIV-associated facial lipoatrophy., Design: A randomized, open-label, single-centre study., Methods: HIV-positive individuals with facial lipoatrophy (based on physician assessment) were randomly assigned to immediate (weeks 0 and 6) or delayed (weeks 12 and 18) PAIG injections administered into the subcutaneous plane. Outcome measures included a change in facial lipoatrophy severity scores (five-point scale), adverse events, photographic assessment, and changes in quality of life (QoL), depression and anxiety using validated surveys., Results: Thirty-one patients (median age 48 years, 97% male) were enrolled and completed 48 weeks of follow-up. Overall, the median volume of product injected bilaterally was 16.0 ml. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of 3 days. There were no cases of necrosis, nodules or infection. Compared with patients randomly assigned to delayed treatment, patients in the immediate therapy group had significantly lower physician-rated facial lipoatrophy scores (0 versus 2; P < 0.0001), improved QoL (P = 0.01), and lower anxiety (P = 0.02) at week 12. At week 48, median physician and patient facial lipoatrophy scores were 0 and 1, respectively, for the entire cohort, and were not significantly different between the groups. Significant improvements in patient anxiety (P = 0.001) and depression (P = 0.01) were observed from baseline to week 48., Conclusion: Treatment with PAIG was effective and safe and led to improvements in facial lipoatrophy grading, QoL, anxiety and depression scores in HIV-infected patients with facial lipoatrophy.