Documentation of psychiatric disorders and related factors in a large sample population of HIV-positive patients in California.

This retrospective cohort study examined electronic medical records of HIV-positive patients in California (N = 7,834) to find the prevalence of any psychiatric condition and the associations between several factors and the likelihood of these disorders. Approximately 53 % of the patients in this study had a documented psychiatric condition, including 23 % who had a mood disorder, 19 % who had a substance-related disorder, and 16 % who had an anxiety disorder. After controlling for potential confounders, significant positive associations (p < 0.001) were found between female gender and the presence of any mood disorder (adjusted odds ratio [95 % confidence interval, 95 %CI] = 1.58 [1.26-1.99]) or anxiety disorder (AOR = 1.54 [1.18-2.02]) and between homosexual orientation and the presence of any psychiatric condition (AOR = 1.33 [1.15-1.55]), mood disorder (AOR = 1.71 [1.42-2.07]), or anxiety disorder (AOR = 1.41 [1.22-1.88]). There were also significant negative associations between African-American race and the presence of any psychiatric condition (AOR = 0.68 [0.60-0.77]), mood disorder (AOR = 0.74 [0.64-0.86]), anxiety disorder (AOR = 0.43 [0.36-0.52]), or substance-related disorder (AOR = 0.78 [0.67-0.91]) and between state/federal insurance and the presence of any psychiatric condition (AOR = 0.70 [0.62-0.79]), mood disorder (AOR = 0.71 [0.62-0.80]), or anxiety disorder (AOR = 0.77 [0.66-0.89]).

Similar efficacy of raltegravir when used with or without a protease inhibitor in treatment-experienced patients.

BACKGROUND: Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population. METHODS: Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥ 16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI. RESULTS: Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/µL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etravirine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05). CONCLUSIONS: In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV.

Meningitis due to hematogenous dissemination of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in a patient with AIDS.

Meningitis due to methicillin-resistant Staphylococcus aureus is a rare clinical presentation but has been well documented in postneurosurgical patients. To our knowledge, no case of methicillin-resistant Staphylococcus aureus meningitis has been previously reported in a nonneurosurgical patient with AIDS. In this case report we describe a person with AIDS who had no history of a neurosurgical procedure, shunt devices, head trauma, or recent hospitalization that presented with methicillin-resistant Staphylococcus aureus meningitis. The infection was successfully treated. Methicillin-resistant Staphylococcus aureusshould be considered in the differential of meningitis in people with AIDS.

Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial.

A putative source of inappropriate immune activation that drives human immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract. Even with effective antiretroviral treatment, residual activation persists. We hypothesized that an oral probiotic could improve the residual immune activation in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086 capsule probiotic in HIV-1-infected persons with suppressed viremia on stable antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10 probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was administered monthly. Blood was tested at the start and end of placebo/probiotic administration for viremia, CD4(+) T cell percentage/concentration, soluble (s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C-reactive protein (CRP), interleukin-8, and tumor necrosis factor-α. All participants maintained viremia <40 RNA copies/ml. The probiotic was safe and well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its administration was associated with a significant increase in the percentage of blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although CD4(+) T cell concentrations were generally unchanged in both groups. None of the biomarkers showed significant changes on probiotic treatment or between-group differences in change (although significance was borderline for a greater sCD163 drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed significant correlations to each other, particularly D-dimer with CRP and sCD14 with tumor necrosis factor (TNF)-α. These data demonstrate the safety and possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved.

Use of maraviroc-, raltegravir-, and etravirine-containing regimens in treatment-experienced patients: a case-series study.

The development of newer agents such as raltegravir, etravirine and maraviroc has improved the perspective of viral load suppression. However, there is not enough data regarding their use together. In this study, we describe nine patients who were triple-class experienced and were on a salvage regimen consisting of a combination of raltegravir, etravirine, and maraviroc. Our results showed that this regimen is safe with no major side effect and has good virological efficacy with two-thirds of the patients achieving an undetectable viral load by 24 weeks.

Barriers and unmet need for supportive services for HIV patients in care in Los Angeles County, California.

Abstract HIV-infected patients frequently experience depression, drug use, and unstable housing but are often unable to access supportive services to manage these challenges. Data on barriers to needed supportive services are critical to improving patient access. Data from the Medical Monitoring Project (MMP), a national supplemental surveillance system for HIV-infected persons in care, was used to examine barriers to support service use and factors associated with need and unmet need for services. Interview data for 333 patients in care in 2007 and 2008 in Los Angeles County (LAC) showed that 71% (n=236) reported needing at least one supportive service and of these, 35% (n=83) reported at least one unmet need for services (46% Latino; 25% white; 83% male; 92% 30+; 77% gay/bisexual; 40% response rate). The main reasons that supportive services were not accessed included lack of information (47%; do not know where to go or who to call); an agency barrier (33%; system too confusing, wait list too long); or a financial/practical barrier (18%; too expensive, transportation problems). In a logistic regression that included all participants (n=333), African Americans (OR=3.1, 95% CI: 1.1-8.7) and those with incomes less than $10,000 were more likely to have service needs (odds ratio [OR]=3.5; 95% confidence interval [CI]: 1.3-9.3). Among those with at least one service need (n=236), those who were gay or bisexual were more likely to report at least one unmet service need (OR=2.8; 95% CI: 1.3-6.1). Disparities were found for need and unmet need for supportive services by race/ethnicity; income and sexual orientation. The reported reasons that services were not obtained suggest needed improvements in information dissemination on availability and location of HIV support services and more streamlined delivery of services.

An unusual pathogen for a liver abscess in a human immunodeficiency virus-infected individual.

Pyogenic liver abscesses are rarely encountered in HIV-infected patients living outside of temperate climates and are usually polymicrobial in nature, with a majority of the pathogens arising from gastrointestinal flora. We describe the second case of a liver abscess in an HIV-positive individual that was caused by methicillin-resistant Staphylococcus aureus (MRSA), most likely due to a partially treated community-acquired MRSA skin abscess. The liver abscess was successfully managed by percutaneous drainage and intravenous antibiotics. This case underlines the ubiquitous nature of community-acquired MRSA and its possible unusual presentations in immunocompromised hosts.

Maraviroc: a new CCR5 antagonist.

Maraviroc is a small molecule and a member of a new class of antiretroviral compounds known as CCR5 antagonists, which block R5-tropic HIV entry into CD4 cells. HIV entry into the cell requires binding to a CD4 molecule and, in the majority of cases, to a coreceptor, either chemokine coreceptor 4 (CXCR4) or 5 (CCR5). In August 2007, the US FDA approved maraviroc for use in combination with other antiretroviral agents for treatment-experienced adults infected with CCR5-tropic HIV-1 only and who have evidence of viral replication. Maraviroc prevents the virus from entering uninfected cells by blocking the CCR5 coreceptor. Maraviroc has two dose formulations (150- and 300-mg tablets) and can be taken with or without food. The dosing recommendations are based on concomitant medications due to drug interactions. It is excreted primarily in the feces, with approximately 25% via urine. The safety and efficacy of maraviroc have not been established in pregnant women or pediatric patients. Maraviroc has been shown to achieve an undetectable HIV-1 RNA level in clinically advanced, class 3 antiretroviral treatment-experienced adults with evidence of CCR5-tropic HIV-1 replication despite ongoing antiretroviral therapy. It is generally well tolerated and its development is responding to a desperate need for new classes of antiretroviral agents that can target novel steps of the HIV lifecycle and do not share crossresistance with currently available therapy.

Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.

Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

Raltegravir: the first in a new class of integrase inhibitors for the treatment of HIV.

Raltegravir (formerly known as MK-0518; Isentress) is the first in a new class of integrase inhibitors approved for the use in treatment-experienced adult patients who have evidence of viral replication and HIV strains resistant to multiple antiretroviral agents. It is dosed twice daily with or without food. Raltegravir is a novel antiretroviral that has been shown to be well tolerated. It has demonstrated potent efficacy in the virologic suppression of HIV-1 RNA levels up to 48 weeks in two controlled studies that were conducted in clinically advanced, three-class antiretroviral, treatment-experienced adults.

Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48.

BACKGROUND: The present primary analysis of AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) compares the efficacy and safety of once-daily darunavir/ritonavir (DRV/r) with that of lopinavir/ritonavir (LPV/r) in treatment-naive patients. METHODS: Patients with HIV-1 RNA at least 5000 copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III, open-label trial, and randomized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg total daily dose (bid or qd) plus fixed-dose tenofovir and emtricitabine for 192 weeks. The primary objective was to demonstrate non-inferiority of DRV/r as compared with LPV/r in HIV-1 RNA less than 50 copies/ml per-protocol time-to-loss of virologic response at 48 weeks. RESULTS: Six hundred and eighty-nine patients were randomized and treated; mean baseline HIV-1 RNA: 4.85 log10 copies/ml and median CD4 count: 225 cells/microl. At 48 weeks, 84% of DRV/r and 78% of LPV/r patients achieved HIV-1 RNA less than 50 copies/ml (estimated difference = 5.6 [95% confidence interval -0.1-11]%), demonstrating non-inferiority of DRV/r as compared with LPV/r (P < 0.001; per-protocol time-to-loss of virologic response). Patients with HIV-1 RNA at least 100 000 copies/ml had a significantly higher response rate with DRV/r (79%) versus LPV/r (67%; P < 0.05). Median CD4 cell count increases (non-completer = failure; cells/mul) were 137 for DRV/r and 141 for LPV/r. DRV/r had a lower incidence of possibly treatment-related grade 2-4 gastrointestinal-related adverse events (7 versus 14%) and treatment-related moderate-to-severe diarrhea (4 versus 10%) than LPV/r. Adverse events leading to discontinuation were DRV/r: 3% and LPV/r: 7%. CONCLUSION: DRV/r 800/100 mg qd was non-inferior to LPV/r 800/200 mg at 48 weeks, with a more favorable safety profile. Significantly higher response rates were observed with DRV/r in patients with HIV-1 RNA at least 100 000 copies/ml. DRV/r 800/100 mg offers a new effective and well tolerated once-daily, first-line treatment option for treatment-naive patients.