Efficacy and safety of raltegravir plus lamivudine maintenance therapy.

BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.

Surveillance of SARS-CoV-2 virus circulation using Acute Respiratory Infections sentinel system of Catalonia (PIDIRAC) during the 2019-2020 season: A retrospective observational study.

BACKGROUND: In the context of COVID-19 pandemic in Catalonia (Spain), the present study analyses respiratory samples collected by the primary care network using Acute Respiratory Infections Sentinel Surveillance System (PIDIRAC) during the 2019-2020 season to complement the pandemic surveillance system in place to detect SARS-CoV-2. The aim of the study is to describe whether SARS-CoV-2 was circulating before the first confirmed case was detected in Catalonia, on February 25th, 2020. METHODS: The study sample was made up of all samples collected by the PIDIRAC primary care network as part of the Influenza and Acute Respiratory Infections (ARI) surveillance system activities. The study on respiratory virus included coronavirus using multiple RT-PCR assays. All positive samples for human coronavirus were subsequently typed for HKU1, OC43, NL63, 229E. Every respiratory sample was frozen at-80°C and retrospectively studied for SARS-CoV-2 detection. A descriptive study was performed, analysing significant differences among variables related to SARS-CoV- 2 cases comparing with rest of coronaviruses cases through a bivariate study with Chi-squared test and statistical significance at 95%. RESULTS: Between October 2019 and April 2020, 878 respiratory samples from patients with acute respiratory infection or influenza syndrome obtained by PIDIRAC were analysed. 51.9% tested positive for influenza virus, 48.1% for other respiratory viruses. SARS-CoV-2 was present in 6 samples. The first positive SARS-CoV-2 case had symptom onset on 2 March 2020. These 6 cases were 3 men and 3 women, aged between 25 and 50 years old. 67% had risk factors, none had previous travel history nor presented viral coinfection. All of them recovered favourably. CONCLUSION: Sentinel Surveillance PIDIRAC enhances global epidemiological surveillance by allowing confirmation of viral circulation and describes the epidemiology of generalized community respiratory viruses' transmission in Catalonia. The system can provide an alert signal when identification of a virus is not achieved in order to take adequate preparedness measures.

Viral Culture Confirmed SARS-CoV-2 Subgenomic RNA Value as a Good Surrogate Marker of Infectivity.

Determining SARS-CoV-2 viral infectivity is crucial for patient clinical assessment and isolation decisions. We assessed subgenomic RNA (sgRNA) as a surrogate marker of SARS-CoV-2 infectivity in SARS-CoV-2-positive reverse transcription PCR (RT-PCR) respiratory samples (n = 105) in comparison with viral culture as the reference standard for virus replication. sgRNA and viral isolation results were concordant in 99/105 cases (94%), indicating highly significant agreement between the two techniques (Cohen's kappa coefficient 0.88, 95% confidence interval [CI] 0.78 to 0.97, P < 0.001). sgRNA RT-PCR showed a sensitivity of 97% and a positive predictive value of 94% to detect replication-competent virus, further supporting sgRNA as a surrogate marker of SARS-CoV-2 infectivity. sgRNA RT-PCR is an accurate, rapid, and affordable technique that can overcome culture and cycle threshold (CT) value limitations and be routinely implemented in hospital laboratories to detect viral infectivity, which is essential for optimizing patient monitoring, the efficacy of treatments/vaccines, and work reincorporation policies, as well as for safely shortening isolation precautions.

Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients.

Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3-27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.

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.

Assessment of RNA amplification by multiplex RT-PCR and IgM detection by indirect and capture ELISAs for the diagnosis of measles and rubella.

The aim of the study was to compare RNA amplification using multiplex RT-PCR and IgM detection by means of indirect and capture ELISAs for the diagnosis of measles and rubella. A total of 229 cases of maculopapular rash with serum and throat swab samples were included. Specific serological IgM to measles and rubella was determined by Enzygnost (Siemens) and Platelia (Bio-Rad). Both viruses were researched using multiplex RT-PCR performed on throat samples. Criteria for inclusion of measles or rubella cases were a positive RT-PCR result for one virus and negative for the other; and/or a positive IgM result for one virus by both ELISAs and negative RT-PCR for the other virus. A total of 74 cases were classified as measles and 54 as rubella. In measles, sensitivity and specificity were 93.2% and 100% for RT-PCR, 97.3% and 98.1% for Enzygnost, and 90.5% and 95.5% for Platelia. For rubella, these values were 42.6% and 100% for RT-PCR, 100% and 97.1% for Enzygnost, and 94.4% and 98.3% for Platelia. Enzygnost and Platelia are useful techniques for detecting IgM against measles and rubella. RNA amplification by RT-PCR was both sensitive and specific for the diagnosis of measles; however, for rubella, the sensitivity of this technique must be improved.

Measles risk groups in Spain: implications for the European measles-elimination target.

The European Region has set itself the goal of eliminating measles by 2010. Incidence has increased in recent years. This study sought to investigate outbreaks in Spain in the period 2005-2007, in order to identify measles-vulnerable groups and compare Spain to other European countries which have also had measles outbreaks. The pattern observed for Spain proved different to that of other European countries, i.e., whereas young adults and infants aged under 15 months were affected in Spain, children aged under 9 years comprised the predominant group in other European countries. Measles cases in Spain reflect low coverage when vaccination began, a pattern that could be repeated in neighbouring countries. Vaccination efforts should thus be targeted at vulnerable groups, namely: young adults; health professionals; travelling communities; and adopted infants and foreigners from countries with important pockets of susceptibles.

Large outbreak of measles in a community with high vaccination coverage: implications for the vaccination schedule.

BACKGROUND: Attempts to eliminate measles from a country or region may be disrupted by an imported case that affects indigenous persons. The objective of this study was to analyze epidemiological and clinical characteristics of a measles outbreak in Catalonia, Spain, in 2006. METHODS: Data on cases of measles reported to the Department of Health, Generalitat of Catalonia, during the period 28 August 2006 through 8 July 2007 were collected. Suspected cases were confirmed by determination of measles-specific immunoglobulin M antibodies and/or detection of virus genome. Incidences were calculated using the estimated population of Catalonia for 2006, and 95% confidence intervals were determined assuming a Poisson distribution. The association between proportions was determined using the chi(2) test and Fisher's exact test. The level of statistical significance was set at alpha = .05. RESULTS: A total of 381 cases were confirmed, for an incidence of 6.6 cases per 100,000 persons. A total of 89.5% of cases occurred in nonvaccinated persons, mainly those aged < or =15 months (incidence, 278.2 cases per 100,000 persons; mean age of patients, 12 months). Indigenous subjects accounted for 89.8% of cases, and laboratory confirmation of results was obtained for 87.1%. Measles genotype D4 was identified in all sequenced samples. CONCLUSIONS: The age distribution of cases of measles among children aged <15 months suggests that the first dose of vaccine should be routinely administered at the age of 12 months.