Simplification to single-tablet regimen of elvitegravir, cobicistat, emtricitabine, tenofovir DF from multi-tablet ritonavir-boosted protease inhibitor plus coformulated emtricitabine and tenofovir DF regimens: week 96 results of STRATEGY-PI.

Background: Antiretroviral therapy (ART) simplification to a single-tablet regimen can benefit HIV-1-infected, virologically suppressed, individuals on ART composed of multiple pills.

Objective: We assessed long-term efficacy and safety of switching to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) from multi-tablet ritonavir-boosted protease inhibitor (PI + RTV) plus F/TDF (TVD) regimens.

Methods: STRATEGY-PI was a 96-week, phase 3b, randomized (2:1), open-label, non-inferiority study examining the efficacy, safety, and tolerability of switching to E/C/F/TDF from PI + RTV + TVD regimens in virologically suppressed individuals (HIV-1 RNA <50 copies/mL).

Telaprevir-based therapy for treatment of HIV-1 and hepatitis C virus co-infected patients: An early access programme.

Objectives: HPC3005 is a multicentre, open-label, telaprevir trial in HCV/HIV coinfected patients with severe fibrosis or compensated cirrhosis.

Methods: Patients were treated with telaprevir 750 mg every 8 h (1125 mg if on efavirenz) plus pegylated interferon-alpha (PEG-IFN, 180 μg once-weekly) and ribavirin (RBV, 800 mg/day) for 12 weeks, followed by 36 weeks of PEG-IFN/RBV.

Results: Mean age was 44 years, 97/118 patients were male and all were Caucasian, 68 had severe fibrosis and 50 had cirrhosis.

Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease.

Objective: To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events.

Design: Prospective cohort.

Methods: EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death.

Direct treatment costs of HIV/AIDS in Portugal.

Objective: To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service.

Methods: A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients' characteristics were collected.

Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.

Background: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.

Methods: VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24.

Change in vitamin D levels and risk of severe vitamin D deficiency over 48 weeks among HIV-1-infected, treatment-naive adults receiving rilpivirine or efavirenz in a Phase III trial (ECHO).

Background: This analysis assessed changes in serum 25-hydroxyvitamin D (25[OH]D; the precursor form of active vitamin D) in antiretroviral-naive adults receiving rilpivirine or efavirenz over 48 weeks in a randomized, double-blind, Phase III trial (ECHO).

Methods: ECHO included 690 patients randomized 1:1 to receive rilpivirine 25 mg once daily (n=346) or efavirenz 600 mg once daily (n=344), plus tenofovir disoproxil fumarate/emtricitabine. 25(OH)D was measured in stored serum samples collected at baseline, and weeks 24 and 48.

Boosted protease inhibitor monotherapy in HIV-infected adults: outputs from a pan-European expert panel meeting.

While the introduction of combination highly active antiretroviral therapy (HAART) regimens represents an important advance in the management of human immunodeficiency virus (HIV)-infected patients, tolerability can be an issue and the use of several different agents may produce problems. The switch of combination HAART to ritonavir-boosted protease inhibitor (PI) monotherapy may offer the opportunity to maintain antiviral efficacy while reducing treatment complexity and the risks of toxicity. Current European AIDS Clinical Society (EACS) guidelines recognise ritonavir-boosted PI monotherapy with twice-daily lopinavir/ritonavir or once-daily darunavir/ritonavir as a possible option in patients who have intolerance to nucleoside reverse transcriptase inhibitors, or for treatment simplification.

Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.

Objectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.

Methods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma immunoglobulin G (IgG) antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells.

Baseline susceptibility of primary HIV-2 to entry inhibitors.

Background: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown.

Methods: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug.

Recent advances in antiretroviral treatment and prevention in HIV-infected patients.

Purpose Of Review: To discuss new antiretroviral agents (ARVs) and alternative ARV treatment strategies that are currently being evaluated, and to provide an overview of the most recent advances in HIV vaccine development.

Recent Findings: There is a continuous need for improvements in ARV therapy (ART) and several new ARVs are currently undergoing clinical investigation, including the non-nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment interruption, induction-maintenance and class-sparing regimens, are also being evaluated and have had varying success to date.

Cell-associated viral burden provides evidence of ongoing viral replication in aviremic HIV-2-infected patients.

Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication.

Envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is associated with disease progression.

Objective: To examine the unspecific and envelope-specific IgA and IgG responses in acute and chronic HIV-2 infection.

Methods: Twenty-eight chronically infected adults and two children with perinatal infection were studied. Total plasma concentrations of IgA and IgG were determined by nephelometry.

The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients.

Background: This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2-4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity

Results: The mean intra-host nucleotide diversity was 2.

Low CD4 T-cell counts despite low levels of circulating HIV: insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease.

A significant proportion of HIV-1+ patients with suppression of viremia under antiretroviral therapy fail to recover CD4(+) T-cell counts (ART-Discordants). Similarly, untreated HIV-2+ patients can also exhibit major CD4 depletion in spite of undetectable viremia. We characterize here the immunological disturbances associated with major CD4-lymphopenia in these two scenarios as compared to untreated viremic HIV-1+ patients with similar CD4-lymphopenia and HIV-1+ patients with successful immunological and virological responses under ART.