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Objectives To determine if switching virologically suppressed patients on a regimen containing lopinavir/r (LPV/r) or fosamprenavir (FPV/r) to darunavir/r (DRV/r) or atazanavir/r (ATV/r) results in improved TGs while maintaining virological suppression. Methods Eligibility criteria were undetectable HIV RNA ≥12 weeks, no PI resistance, receiving LPV/r ( n = 46) or FPV/r ( n = 3) plus nucleosides, and fasting TGs >200 mg/dl. Patients were randomized to either QD ATV/r or DRV/r (maintaining the same nucleosides). Primary endpoint was change in TGs from baseline to week 24. Results 66 were screened, 51 enrolled and two withdrew consent after randomization. 24 patients received ATV/r; 25 received DRV/r. Baseline mean CD4 cell count was 569; HIV RNA was p Conclusions Patients with high TGs who switched from LPV/r or FPV/r to DRV/r or ATV/r had improved TGs, while maintaining virological suppression and high adherence and QOL.

Objective This paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naive HIV-1-infected adults. Methods ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. Results Of 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA Conclusion Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naive patients.

Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA(R)), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA

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.

Darunavir (formerly known as TMC 114) is a protease inhibitor that was approved by the US FDA in June 2006 for use in treatment-experienced patients, with markedly greater virological and immunological benefits compared with the standard of care. It is dosed twice daily with food and requires boosting with ritonavir. It has demonstrated virological efficacy in vivo, with activity against protease inhibitor-resistant HIV, and in treatment-naive patients in clinical studies with up to 48-week follow-up in combination with an optimized background regimen. Darunavir used with low-dose ritonavir is a largely well-tolerated protease inhibitor with proven efficacy.

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.

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

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.

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]).

Patients virologically suppressed on TDF/FTC + ATV/r may require alternative regimens that maintain suppression while addressing some drug-related side effects. We explored two alternative regimens that replace RTV and/or TDF/FTC. This open-label exploratory pilot trial enrolled 43 patients on TDF/FTC + ATV/r. Subjects were randomized to one of three arms. Arm 1 (n=15) replaced TDF/FTC with RAL 400 mg BID while continuing ATV/r. Arm 2 (n=14) made two changes: TDF/FTC was stopped and RAL BID was used instead; ritonavir was stopped and ATV 300 mg BID was used. Arm CTL (n=14) continued the baseline (BL) regimen. The week 48 final endpoint is summarized. The primary endpoint was maintaining virologic suppression ( 200 c/mL on two consecutive tests) were on arm 2; both reported adherence problems and no resistance mutations were detected. Overall CD4 counts were 534/mm 3 at BL and 555/mm 3 at week 48. There was a significant CD4 cell count difference favoring CTL (+52/mm 3 ) vs. arm 2 (-14/mm 3 ), p=0.03. No significant differences across arms were noted in lipid fractions or other lab tests. There were no clinically significant EKG changes across arms. Among AEs of interest through week 48, there were more neurologic AEs on arm 1 (n=7) and 2 (n=6) vs. CTL (n=1), and more musculoskeletal events noted on arm 2 (n=7) vs. arm 1 (n=3) and CTL (n=1). Quality of life was measured with a self-assessment Likert scale. Scores were similar across arms despite the BID dosing in two arms. Self-reported adherence using 3-day recall was >95% in all three arms at both baseline and week 48. In this randomized pilot study, two of the three arms maintained virologic suppression in all subjects; there were two virologic rebounds in arm 2. No resistance mutations were detected in either, and adherence issues were noted for both subjects. We also noted that the CD4 cell change was significantly less on arm 2, and there were more neurologic and musculoskeletal AEs on arm 2 vs. CTL. In this study, the use of ATV/r with either TDF/FTC or RAL was successful over 48 weeks, but unboosted BID ATV 300 mg + BID RAL 400 mg as an alternative in virologically suppressed patients should be used with caution. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Cohen C et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18279 http://www.jiasociety.org/index.php/jias/article/view/18279 | http://dx.doi.org/10.7448/IAS.15.6.18279

Background Although the durability of antiretroviral (ARV) efficacy has improved, mainly due to better tolerability, ease of administration (adherence) and potency, some patients still encounter virological and immunological treatment failure. These patients have been on multiple regimens containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitor (NNRTI) and Protease Inhibitor (PI) and have become resistant to one or more of these classes. Hence, the need for salvage therapies using newly approved antiretrovirals that are NRTI, NNRTI and PI sparing is a clinical reality. Raltegravir, maraviroc and etravirine are 3 new agents with distinguished characteristics which are now available however guidelines for their use continue to evolve and none exist yet on using them all in combination. In this study we reviewed patients who were four ARV class experienced and on salvage regimens consisting of a combination of raltegravir, etravirine and maraviroc.

This letter to the editor discusses the results of a Development of Antiretroviral Therapy in Africa (DART) study which found that little survival benefit was attained with laboratory monitoring as opposed to clinical monitoring alone in the care of HIV-infected patients. It states that the DART results suggest that a high level of health may be attained and sustained without routine laboratory monitoring and up to one-third more HIV-infected people could be treated with the money saved.

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.

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.

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.

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.

Background: Approximately 30% of HIV-infected patients are co-infected with hepatitis C (HCV). The current treatment standard of care for HCV, pegylated interferon and ribavirin (RBV), has demonstrated a sustained virologic response (SVR) in less than 50% of HCV/HIV co-infected patients, and only 17-35% in HCV genotype 1 patients. It has been previously shown that using a weight-based RBV dose results in favorable SVR rates. Prior studies suggest that HCV/HIV co-infected patients receiving a HAART regimen that included tenofovir (TDF) had higher SVR rates than those who received abacavir (ABC) in their nucleos(t)ide analogue (N(t)RTI) backbone. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P211 Cite this article as: Bhatti et al.: Response to treatment of hepatitis C in HCV/HIV co-infected patients is not influenced by either abacavir or tenofovir with weight-based ribavirin. Journal of the International AIDS Society 2010 13(Suppl 4):P211. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112996/

ARTEMIS was a Phase III, randomised, open-label study assessing efficacy and safety of DRV/r 800/100mg qd versus LPV/r 800/200mg total daily dose (qd or bid) in treatment-naive HIV-1-infected adults. At 96 wks, DRV/r demonstrated non-inferiority and superiority to LPV/r in virological response. Wk 192 results are reported. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P3 Cite this article as: Orkin et al.: ARTEMIS: 192-week efficacy and safety of once-daily darunavir/ritonavir (DRV/r) vs lopinavir/r (LPV/r) in treatment-naive HIV-1-infected adults. Journal of the International AIDS Society 2010 13(Suppl 4):P3. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113031/