Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens.

OBJECTIVES: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. METHODS: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. RESULTS: We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%-4.3%), 4.7% (95% CI 2.2%-7.1%) and 7.6% (95% CI 5.4%-9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3-0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. CONCLUSIONS: In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 µg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral response.

Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study.

Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy.

OBJECTIVE: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent. DESIGN: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks. METHODS: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6). RESULTS: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints. CONCLUSION: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review.

BACKGROUND: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. METHODS: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. RESULTS: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. CONCLUSIONS: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Clinical characteristics, risk factors, and incidence of symptomatic coronavirus disease 2019 in a large cohort of adults living with HIV: a single-center, prospective observational study.

BACKGROUND: It is unclear how characteristics, risk factors, and incidence of coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) differ from the general population. METHODS: Prospective observational single-center cohort study of adult PLWH reporting symptoms of COVID-19. We assessed clinical characteristics, risk factors for COVID-19 diagnosis and severity, and standardized incidence rate ratio for COVID-19 cases in PLWH cohort and in Barcelona. RESULTS: From 1 March 2020 to 10 May 2020, 53 out of 5683 (0.9% confidence interval 0.7-1.2%) PLWH were diagnosed with COVID-19. Median age was 44 years, CD4 T cells were 618/µl and CD4/CD8 was 0.90. All but two individuals were virologically suppressed. Cough (87%) and fever (82%) were the most common symptoms. Twenty-six (49%) were admitted, six (14%) had severe disease, four (8%) required ICU admission, and two (4%) died. Several laboratory markers (lower O2 saturation and platelets, and higher leukocytes, creatinine, lactate dehydrogenase, C reactive protein, procalcitonin, and ferritin) were associated with COVID-19 severity. No HIV or antiretroviral-related factors were associated with COVID-19 diagnosis or severity. Standardized incidence rate ratios of confirmed or confirmed/probable COVID-19 in PLWH were 38% (95% confidence interval 27-52%, P < 0.0001) and 33% (95% confidence interval 21-50%, P < 0.0001), respectively relative to the general population. CONCLUSION: PLWH with COVID-19 did not differ from the rest of the HIV cohort. Clinical presentation, severity rate, and mortality were not dependent on any HIV-related or antiretroviral-related factor. COVID-19 standardized incidence rate was lower in PLWH than in the general population. These findings should be confirmed in larger multicenter cohort studies.

Estimating the HIV undiagnosed population in Catalonia, Spain: descriptive and comparative data analysis to identify differences in MSM stratified by migrant and Spanish-born population.

OBJECTIVE: Undiagnosed HIV continues to be a hindrance to efforts aimed at reducing incidence of HIV. The objective of this study was to provide an estimate of the HIV undiagnosed population in Catalonia and compare the HIV care cascade with this step included between high-risk populations. METHODS: To estimate HIV incidence, time between infection and diagnosis and the undiagnosed population stratified by CD4 count, we used the ECDC HIV Modelling Tool V.1.2.2. This model uses data on new HIV and AIDS diagnoses from the Catalan HIV/AIDS surveillance system from 2001 to 2013. Data used to estimate the proportion of people enrolled, on ART and virally suppressed in the HIV care cascade were derived from the PISCIS cohort. RESULTS: The total number of people living with HIV (PLHIV) in Catalonia in 2013 was 34 729 (32 740 to 36 827), with 12.3% (11.8 to 18.1) of whom were undiagnosed. By 2013, there were 8458 (8101 to 9079) Spanish-born men who have sex with men (MSM) and 2538 (2334 to 2918) migrant MSM living with HIV in Catalonia. A greater proportion of migrant MSM than local MSM was undiagnosed (32% vs 22%). In the subsequent steps of the HIV care cascade, migrants MSM experience greater losses than the Spanish-born MSM: in retention in care (74% vs 55%), in the proportion on combination antiretroviral treatment (70% vs 50%) and virally suppressed (65% vs 46%). CONCLUSIONS: By the end of 2013, there were an estimated 34 729 PLHIV in Catalonia, of whom 4271 were still undiagnosed. This study shows that the Catalan epidemic of HIV has continued to expand with the key group sustaining HIV transmission being MSM living with undiagnosed HIV.

Occlusive vasculopathy in human immunodeficiency virus (HIV)-associated vasculitis: unusual clinical and imaging course.

Human immunodeficiency virus (HIV)-associated vasculitis is a rare secondary systemic vasculitis involving small and medium arteries. We report a 42-year-old man with uncontrolled HIV infection presenting with long-lasting abdominal pain. An abdominal CT angiography revealed multiple microaneurysms and stenoses in intrarenal arteries, with involvement of mesenteric and hepatic arteries. HIV-associated vasculitis was diagnosed and glucocorticoids and raltegravir-based antiretroviral therapy were administered with good initial clinical and virological response. Several episodes of acute intestinal ischaemia were later developed requiring bowel resections of which histological examination showed vascular occlusive fibrotic changes without active vasculitic lesions. Vasculitis persisted in remission and intrarenal microaneurysms disappeared.

Mortality, Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort.

INTRODUCTION: Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. MATERIALS AND METHODS: We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. MORTALITY RESULTS: 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower [1.7/1000 py; (1.0-2.4/1000 py)]. SURVIVAL RESULTS: Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versus MSM. CONCLUSION AND RECOMMENDATION: There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.

Epidemiology of infections by HIV, Syphilis, Gonorrhea and Lymphogranuloma Venereum in Barcelona City: a population-based incidence study.

BACKGROUND: The aim of this study was to determine the evolution of HIV infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their epidemiological characteristics in Barcelona city. METHODS: Population-based incidence study of all newly occurring diagnoses of HIV infection, syphilis, gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A descriptive analysis was performed. The annual incidence rates per 100,000 inhabitants were calculated by sex, sexual conduct and educational level. To estimate global sex-specific rates we used the Barcelona city census; for the calculation of rates by sexual conduct and educational level we used estimates of the Barcelona Health Interview Survey. Trends were analysed using the chi-squared test for linear trend. RESULTS: HIV. 66.8 % of the HIV cases were men who had sex with men (MSM). The incidence rates in MSM over the study period were from 692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh. and the MSM with a university education ranged from 196.3/100,000 to 1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with university education ranged from 176.7/100,000 to 530.1/100,000 inh.. Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with university education ranged from 9.3/100,000 to 265/100,000 inh. CONCLUSION: An increase in cases of STI was observed. These STI mainly affected MSM with a university education. Continuing to monitor changes in the epidemiology of STI, and identifying the most affected groups should permit redesigning preventive programs, with the goal of finding the most efficient way to reach these population groups.

Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection.

BACKGROUND: Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir. METHODS: Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally. RESULTS: Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4 T-cell counts was higher in the +MVC arm. Conversely, CD8 T-cell counts and CD4 T-cell activation decreased slower in the +MVC arm. Absolute CD4 T-cell and CD8 T-cell counts, immune activation, CD4/CD8 T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study. CONCLUSION: Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR newly infected cells and recovery of CD4 T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.

Epidemiological characteristics and predictors of late presentation of HIV infection in Barcelona (Spain) during the period 2001-2009.

BACKGROUND: Early diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09. METHODS: Demographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation. RESULTS: Of the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002). CONCLUSION: Late presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.

A new multidisciplinary home care telemedicine system to monitor stable chronic human immunodeficiency virus-infected patients: a randomized study.

BACKGROUND: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. METHODOLOGY: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. FINDINGS: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4+ T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels >90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. CONCLUSIONS: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection. TRIAL REGISTRATION: Clinical-Trials.gov: NCT01117675.

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain).

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.