Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE / ATV/r+RAL (DT) after failure with NNRTI

Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba-sado en INNTR.ClinicalTrials.gov, Número: NCT01829802.Método: Estudio piloto abierto, multicéntrico y aleatoriza-do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta-dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue-ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues-ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/µL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H).Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802

Background: Dual therapy has emerged as a novel concept for HIV treatment. This study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.Methods: Randomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.Results: Out of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/µL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802

Retention among transgender women treated with dolutegravir associated with tenofovir/lamivudine or emtricitabine in Argentina: TransViiV study.

In Argentina, transgender women (TGW) have a high HIV prevalence (34%). However, this population shows lower levels of adherence, retention in HIV care and viral suppression than cisgender patients. The World Health Organization (WHO) recommends the transition to dolutegravir (DTG)-based regimens to reduce adverse events and improve adherence and retention. The purpose of this study was to determine retention, adherence and viral suppression in naïve TGW starting a DTG-based first-line antiretroviral treatment (ART) and to identify clinical and psychosocial factors associated with retention. We designed a prospective, open-label, single-arm trial among ART-naïve HIV positive TGW (Clinical Trial Number: NCT03033836). Participants were followed at weeks 4, 8, 12, 24, 36 and 48, in a trans-affirmative HIV care service that included peer navigators, between December, 2015 and May, 2019. Retention was defined as the proportion of TGW retained at week 48 and adherence was self-reported. Viral suppression at <50 copies/mL was evaluated using snapshot algorithm and as per protocol analysis. Of 75 TGW screened, 61 were enrolled. At baseline, median age was 28 y/o., HIV-1-RNA (pVL) 46,908 copies/mL and CD4+ T-cell count 383 cells/mm3. At week 48, 77% were retained and 72% had viral suppression (97% per protocol). The regimen was well tolerated and participants reported high adherence (about 95%). Eleven of the fourteen TGW who discontinued or were lost to follow-up had undetectable pVL at their last visit. Older age was associated with better retention. DTG-based treatment delivered by a trans-competent team in a trans-affirmative service was safe and well tolerated by TGW and associated with high retention, high adherence and high viral suppression at 48 weeks among those being retained.

Techniques for Self-Cannulation.

Abstract.

Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy.

BACKGROUND: Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). METHODS: In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ±â€…ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. RESULTS: Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. CONCLUSIONS: Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

The Decline in Community Preceptor Teaching Activity: Exploring the Perspectives of Pediatricians Who No Longer Teach Medical Students.

PURPOSE: Difficulty in recruiting and retaining community preceptors for medical student education has been described in the literature. Yet little, if any, information is known about community outpatient preceptors who have stopped or decreased teaching time with students. This study aimed to examine these preceptors' perspectives about this phenomenon. METHOD: Using a phenomenology framework, this multi-institutional qualitative study used semistructured interviews with community pediatric preceptors who had stopped or reduced teaching time with medical students. Interviews were conducted between October 2017 and January 2018 and transcribed verbatim. Interviews explored factors for engaging in teaching, or decreasing or ceasing teaching, that would enable future teaching. An initial code book was developed and refined as data were analyzed to generate themes. RESULTS: Twenty-seven community pediatricians affiliated with 10 institutions participated. Thirty-seven codes resulted in 4 organizing themes: evolution of health care, personal barriers, educational system, and ideal situations to recruit and retain preceptors, each with subthemes. CONCLUSIONS: From the viewpoints of physicians who had decreased or stopped teaching students, this study more deeply explores previously described reasons contributing to the decline of community preceptors, adds newly described barriers, and offers strategies to help counter this phenomenon based on preceptors' perceptions. These findings appear to be manifestations of deeper issues including the professional identify of clinical educators. Understanding the barriers and strategies and how they relate to preceptors themselves should better inform education leaders to more effectively halt the decline of community precepting and enhance the clinical precepting environment for medical students.

An Interview with Neiltje Gedney - Home Dialyzor and Patient Advocate.

This article describes one woman's journey to home hemodialysis therapy. Her training and trials in adjusting to the therapy led to a passion for promoting improvements in dialysis for herself and others. Ms. Gedney has become a patient advocate who travels the country speaking for home dialyzers to politicians, physicians, and an alphabet soup of renal care committees. Her example should inspire others in the renal care community to speak out to make a difference for positive change.

Fostemsavir: a new CD4 attachment inhibitor.

PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21-1.73 log10 copies/ml from baseline after 8 days of functional monotherapy; at 48 weeks, up to 82% of patients treated with FTR and an optimized background ARV regimen achieved virological suppression below 50 copies/ml. SUMMARY: FTR is an investigational HIV drug with a novel mechanism of action that demonstrates virologic activity in HIV-infected treatment-experienced individuals.

Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study.

INTRODUCTION: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. METHODS: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). RESULTS: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180-462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients. CONCLUSIONS: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. CLINICALTRIALS.GOV IDENTIFIER: NCT02211482.

Recruiting and Retaining Community-Based Preceptors: A Multicenter Qualitative Action Study of Pediatric Preceptors.

PURPOSE: The recruitment and retention of community preceptors to teach medical students is difficult. The authors sought to characterize the underlying motivational factors for becoming a preceptor and to identify strategies for recruiting and retaining community-based pediatric preceptors. METHOD: This multicenter qualitative action study included semistructured interviews with community-based pediatric preceptors affiliated with 12 institutions from August to December 2015. Only active preceptors were included, and participating institutions were diverse with respect to geographic location and class size. Interviews were conducted over the telephone and transcribed verbatim. Six investigators used deidentified transcripts to develop a codebook. Through a constant comparative method, codes were revised as data were analyzed and disagreements were resolved through discussion. All investigators organized the themes into dimensions. RESULTS: Fifty-one preceptors were interviewed. Forty-one themes coalesced into four dimensions: (1) least liked aspects of teaching, (2) preparation to teach, (3) inspiration to teach, and (4) ways to improve recruitment and retention. Time constraints and patient care demands were the most commonly cited deterrents to teaching. Successful preceptors balanced their clinical demands with their desire to teach using creative scheduling. External rewards (e.g., recognition, continuing medical education credit) served as incentives. Internal motivation inspired participants to share their enthusiasm for pediatrics and to develop longitudinal relationships with their learners. CONCLUSIONS: Changes in health care delivery have imposed more time constraints on community-based preceptors. However, this study identified underlying factors motivating physicians to volunteer as preceptors. Strategies to recruit new and retain current preceptors must be collaborative.

Modification of the HIV-specific CD8+ T-cell response in an HIV elite controller after chikungunya virus infection.

OBJECTIVE: To evaluate the impact of chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8 T-cell (CTL) response in an HIV elite controller. DESIGN: Three blood samples were obtained from an elite controller at 27 days (EC-CHIKV, Sample 1, S1), 41 days (S2) and 1 year (S3) after CHIKV infection. Additionally, samples from another nine elite controllers and nine viremic chronics were obtained. METHODS: CD4 T-cell counts, viral load and immune activation were recorded. Natural killer (NK) cells and HIV-specific CTL quality were evaluated. Data were analyzed using nonparametric statistics. RESULTS: A male HIV elite controller was confirmed for CHIKV infection. At S1, he presented 211 cells/µl CD4 T-cell count, a HIV viral load blip (145 copies/ml) and high T-cell activation. NK cell percentage and activation were higher at S2. All parameters were recovered by S3. CTLs at S1 were exclusively monofunctional with a high proportion (>80%) of degranulating CTLs. By S3, CTL polyfunctionality was more similar to that of a typical elite controller. The distribution of CTL memory subsets also displayed altered profiles. CONCLUSION: The results showed that the phenotype and function of HIV-specific CTLs were modified in temporal association with an HIV viral load blip that followed CHIKV infection. This might have helped to control the transient HIV rebound. Additionally, NK cells could have been involved in this control. These results provide useful information to help understand how elite controllers maintain their status, control HIV infection and alert about the negative impact to the immune function of HIV-infected individuals living in CHIKV endemic areas.

Human factors engineering and design validation for the redesigned follitropin alfa pen injection device.

OBJECTIVES: To demonstrate, using human factors engineering (HFE), that a redesigned, pre-filled, ready-to-use, pre-asembled follitropin alfa pen can be used to administer prescribed follitropin alfa doses safely and accurately. METHODS: A failure modes and effects analysis identified hazards and harms potentially caused by use errors; risk-control measures were implemented to ensure acceptable device use risk management. Participants were women with infertility, their significant others, and fertility nurse (FN) professionals. Preliminary testing included 'Instructions for Use' (IFU) and pre-validation studies. Validation studies used simulated injections in a representative use environment; participants received prior training on pen use. RESULTS: User performance in preliminary testing led to IFU revisions and a change to outer needle cap design to mitigate needle stick potential. In the first validation study (49 users, 343 simulated injections), in the FN group, one observed critical use error resulted in a device design modification and another in an IFU change. A second validation study tested the mitigation strategies; previously reported use errors were not repeated. CONCLUSIONS: Through an iterative process involving a series of studies, modifications were made to the pen design and IFU. Simulated-use testing demonstrated that the redesigned pen can be used to administer follitropin alfa effectively and safely.

Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study.

INTRODUCTION: Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. MATERIALS AND METHODS: The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. RESULTS: Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC. CONCLUSION: Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL-C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction (1). So, the DT strategy, even missing the lipid-lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.

Switching to nevirapine-based regimens after undetectable viral load is not associated with increased risk of discontinuation due to toxicity.

INTRODUCTION: Due to its good tolerability, favourable cardiovascular risk-profile, low-pill burden and cost, nevirapine-based regimens are an attractive simplification strategy for patients with suppressed viral load (VL). However, current guidelines recommend caution if nevirapine (NVP) is prescribed in males and females with CD4 counts above 400 or 250 cells/µL, respectively. The aim of this study is to determine the prevalence and risk factors associated with development of toxicity or treatment discontinuation in patients switching to NVP-based regimens. MATERIALS AND METHODS: Retrospective chart review of HIV-infected patients with suppressed VL who switched from a PI-based regimen to a NVP-based regimen in four HIV clinics in Argentina, between 1997 and 2013. Bivariate and multivariate analyses were performed to explore factors associated with treatment discontinuation. High CD4 count was defined as CD4-cell count ≥400 or 250 cells/µL in males and females, respectively. RESULTS: Of 218 patients included, 165 (75.7%) were male; 21 (9.6%) were co-infected with HCV and/or HBV. Median baseline (BSL) CD4 count: 138 cells/µL (IQR: 64-276). At switch, patients had a median age of 38 years (IQR: 33.4-43.8) and had been suppressed for a median of 1.4 years (IQR: 0.6-2.2); 138 patients (63.3%) had high CD4-cell counts: among females, median CD4 count at switch was 462 (IQR: 330-709) cells/µL; among males, 433 (IQR: 305-595) cells/µL. Thirty-six patients (13.5%) presented NVP-related toxicity (30 skin toxicity, 6 hepatic toxicity), 29 (13.3%) discontinued NVP. Median time to development to toxicity: 32 days (IQR: 15-75). In bivariate analysis, chronic hepatitis was the only variable associated with development of toxicity (OR: 2.90, 95% CI 1.08-7.78). In multivariate analysis, no statistical significant associations were observed between either development of toxicity or treatment discontinuation and gender, chronic hepatitis, age or CD4-cell count at BSL or at switch (all p>0.05). CONCLUSIONS: In our study, switching to a NVP-based regimen in patients with undetectable VL was associated with a low incidence of skin or liver toxicity, and treatment discontinuation. Moreover, these were unrelated to the CD4-cell count. Our findings suggest that, in contrast with ART-naïve patients, switching to NVP-based regimens could be a safe strategy for patients with suppressed viremia regardless of the CD4-cell count.

Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease.

BACKGROUND: Regulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development. METHODS: The Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data. RESULTS: The literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011. CONCLUSIONS: We summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.

Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.

BACKGROUND: Daily oral triple therapy is effective at halting HIV disease progression, but can have toxic effects and is costly. We investigated whether dual therapy with lopinavir and ritonavir plus lamivudine is non-inferior to standard triple therapy. METHODS: The GARDEL study (Global AntiRetroviral Design Encompassing Lopinavir/r and Lamivudine vs LPV/r based standard therapy) is a 48 week, phase 3, randomised, controlled, open-label, non-inferiority trial in antiretroviral-therapy-naive adults (age ≥18 years) with documented HIV-1 RNA viral load of at least 1000 copies per mL. The study was done at 19 centres in six countries. Patients were randomly assigned (1:1) to dual therapy or triple therapy by sealed envelopes, in blocks of four, stratified by baseline viral load (<100,000 vs ≥100,000 copies per mL). Dual therapy consisted of lopinavir 400 mg and ritonavir 100 mg plus lamivudine 150 mg, both twice daily. Triple therapy consisted of lopinavir 400 mg and ritonavir 100 mg twice daily and lamivudine or emtricitabine plus another nucleoside reverse transcriptase inhibitor (NRTI) in fixed-dose combination. Efficacy was analysed in all participants who received at least one dose of study drug. The primary endpoint was virological response rate, defined as the proportion of patients with HIV RNA less than 50 copies per mL at 48 weeks. Dual therapy was classed as non-inferior to triple therapy if the lower bound of the 95% CI for the difference between groups was no lower than -12%. Patients and investigators were unmasked to treatment allocation. This study is registered with ClinicalTrials.gov, number NCT01237444. FINDINGS: Between Dec 10, 2010, and May 15, 2012, 217 patients were randomly assigned to the dual-therapy group and 209 to the triple-therapy group. 198 patients in the dual-therapy group and 175 in the triple-therapy group completed 48 weeks of treatment. At week 48, 189 patients (88·3%) in the dual-therapy group and 169 (83·7%) in the triple-therapy group had viral response (difference 4·6%, 95% CI -2·2 to 11·8; p=0·171). Patients with baseline viral load of at least 100,000 copies per mL showed similar results (87·2% vs 77·9%, respectively; difference 9·3%, 95% CI -2·8 to 21·5; p=0·145). Toxicity-related or tolerability-related discontinuations were more common in the triple-therapy group (n=10 [4·9%]) than in the dual-therapy group (n=1 [0·4%]; difference 4·5%, 95% CI -8·1 to -0·9; p=0·011). 65 adverse events in the dual-therapy group and 88 in the triple-therapy group were possibly or probably drug related (p=0·007). Two serious adverse events occurred, both in the dual-therapy arm, one of which (a case of gastritis) was reported as possibly or probably related to drug treatment. INTERPRETATION: Dual therapy with lopinavir and ritonavir plus lamivudine regimen warrants further clinical research and consideration as a potential therapeutic option for antiretroviral-therapy-naive patients. FUNDING: Fundación Huésped and AbbVie.

Treatment as prevention: are Argentinean HIV care providers willing to adopt earlier antiretroviral therapy?

HIV guidelines increasingly recommend antiretroviral therapy (ART) initiation at a higher CD4 levels. The extent to which these evolving standards are translated into routine clinical care has not been evaluated in Argentina. During October 2012, we conducted an online survey among Argentinean HIV clinicians to assess their attitudes and practices toward ART initiation and its potential use for HIV prevention. Of the 280 physicians included, 61% would prescribe ART at CD4 ≤ 500 cells/µL for asymptomatic patients. Although, only 11% would recommend ART irrespective of CD4 cell count, 72% would do it for serodiscordant couples, and 75% for sex workers. Most participants agreed that they would consider earlier initiation of ART if transmission risk exists, and that expansion of ART could help decrease HIV incidence. These results suggest that a large proportion of Argentinean HIV care providers are willing to adopt the recently updated Argentinean guidelines recommending earlier ART, especially when high HIV transmission risk exists.

Design validation and labeling comprehension study for a new epinephrine autoinjector.

BACKGROUND: To facilitate the correct use of epinephrine autoinjectors (EAIs) by patients and caregivers, a novel EAI (Auvi-Q) was designed to help minimize use-related hazards. OBJECTIVE: To support validation of Auvi-Q final design and assess whether the instructions for use in the patient information leaflet (PIL) are effective in training participants on proper use of Auvi-Q. METHODS: Healthy participants, 20 adult and 20 pediatric, were assessed for their ability to complete a simulated injection by following the Auvi-Q instructions for use. Participants relied only on the contents of the PIL and other labeling features (device labeling and its instructions for use, electronic voice instructions and visual prompts). RESULTS: The mean ± SD age of the adult and pediatric participants was 39.4 ± 11.6 and 10.9 ± 2.3 years, respectively. In total, 80% of adult and 35% of pediatric participants had prior experience with EAIs. All adults and 95% of pediatric participants completed a simulated injection on the first attempt; 1 pediatric participant required parental training and a second attempt. Three adult and 4 pediatric participants exhibited a noncritical issue while successfully completing the simulated injection. Most participants agreed that the injection steps were easy to follow and the PIL facilitated understanding on using Auvi-Q safely and effectively. CONCLUSION: The PIL and other labeling features were effective in communicating instructions for successful use of Auvi-Q. This study provided validation support for the final design and anticipated instructions for use of Auvi-Q.

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

OBJECTIVES: To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. METHODS: This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). RESULTS: Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. CONCLUSION: At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in virologically-suppressed patients merits further prospective long-term evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159224.