The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort.

HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients

Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicidal Ideation or Attempted or Completed Suicide: An Analysis of Trial Data

The relationship between efavirenz use and suicidality is not well defined

Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-Thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median prechemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. © 2014 Cillo et al

Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research

<p>Abstract</p> <p>Background</p> <p>There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies.</p> <p>Methods</p> <p>Sixteen studies, all observational, were identified using a standard citation search. They fulfilled the following inclusion criteria: conducted in the HAART era; sample size > 10; treatment effect involved more than one antiretroviral and none had a retrospective design. The qualitative phase of review of these studies consisted of (i) a blind assessment rating studies on features such as sample size, statistical methods and definitions of neuroHAART, and (ii) a non-blind assessment of the sensitivity of the neuropsychological methods to HIV-associated neurocognitive disorder (HAND). During quantitative evaluation we assessed the statistical power of studies, which achieved a high rating in the qualitative analysis. The objective of the power analysis was to determine the studies ability to assess their proposed research aims.</p> <p>Results</p> <p>After studies with at least three limitations were excluded in the qualitative phase, six studies remained. All six found a positive effect of neuroHAART on neurocognitive function or CSF HIV suppression. Of these six studies, only two had statistical power of at least 80%.</p> <p>Conclusions</p> <p>Studies assessed as using more rigorous methods found that neuroHAART was effective in improving neurocognitive function and decreasing CSF viral load, but only two of those studies were adequately statistically powered. Because all of these studies were observational, they represent a less compelling evidence base than randomised control trials for assessing treatment effect. Therefore, large randomised trials are needed to determine the robustness of any neuroHAART effect. However, such trials must be longitudinal, include the full spectrum of HAND, ideally carefully control for co-morbidities, and be based on optimal neuropsychology methods.</p

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity

<p>Abstract</p> <p>Background</p> <p>Central nervous system (CNS) infection is a nearly universal feature of untreated systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment.</p> <p>Results</p> <p>After establishing an <it>accurate mass and time </it>(AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral therapy and correlated abundances of identified proteins a) within and between subjects, b) with all other proteins across the entire sample set, and c) with "external" CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) ≤ -0.3 and ≥0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node.</p> <p>Conclusions</p> <p>Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.</p