Suchergebnisse

AbstractIntroduction: 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.

IntroductionTreatment 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 MethodsThe 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.ResultsPatient'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.ConclusionChanges 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.

BackgroundTuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to Mycobacterium tuberculosis (Mtb), we assessed basal and Mtb‐induced proliferation, cytokine production, and expression of signalling lymphocytic activation molecule (SLAM), inducible costimulator (ICOS) and programmed death‐1 (PD‐1) on T lymphocytes from HIV‐positive individuals coinfected with TB, HIV‐positive subjects, TB patients and healthy donors (HD).FindingsHIV‐TB patients showed increased ICOS, SLAM and PD‐1 basal levels on T lymphocytes, whereas HIV‐positive individuals displayed elevated levels of SLAM and PD‐1, TB patients high levels of SLAM, and HD low levels of the three proteins. Mtb‐stimulation enhanced ICOS expression in the four groups, but only TB and HD increased SLAM and PD‐1 levels.ConclusionsThese data show the immune deregulation that takes place during the immune response against TB in different study populations.

AbstractIntroduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.Methods: We searched PubMed, in addition to hand‐review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low‐ and middle‐income countries (LMICs) published in the last fifteen years.Results and Discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease‐of‐use, suitability for application and distribution in LMIC, and throughput for high‐volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI – evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point‐of‐care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre‐exposure prophylaxis outcomes by avoiding treatment initiation for HIV‐seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting.Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale‐up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point‐of‐care diagnostics, and efficacious and effective first‐line regimens.

BackgroundDiagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial.MethodsOur objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI‐patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT‐CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients.ResultsAmong 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non‐AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12‐month progression rate among untreated patients with ARS was 34% (95% CI 22.5‐46.3) versus 13% (95% CI 1.1‐24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT‐CD4 < 350 cells/mm3, and baseline and six‐month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97‐73.42) and 9.44 (95% CI 1.38‐64.68), respectively.ConclusionsIn Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.