Impact of coronavirus disease 2019 epidemics on prevention and care for HIV and other sexually transmitted infections.

OBJECTIVE: To assess the impact of coronavirus disease 2019 (COVID-19) epidemics on the prevention and care for HIV and other sexually transmitted infections at a major reference centre providing preventive and clinical services in Catalonia, Spain. DESIGN: We retrospectively compared anonymized clinical and laboratory data from March to December 2020 vs. 2019. METHODS: Monthly clinical data on HIV preexposure and postexposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae,and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database. RESULTS: There were less (↓28%, P  = 0.003) but more advanced (mean CD4+ cells/µl 305 vs. 370, P  < 0.001) HIV infections and more gonorrhoea (↑39%, P  < 0.001) and chlamydia (↑37%, P  < 0.001) infections in 2020 vs. 2019. In people with HIV, rates of HIV RNA less than 50 copies/ml remained stable (11 vs. 11%, P  = 0.147) despite less scheduled visits (↓25%, P  < 0.001). However, they had less antiretroviral prescription changes (↓10%, P  = 0.018), worse plasma lipids [mean total cholesterol 190 vs. 185 mg/dl, P  < 0.001;mean low-density lipoprotein (LDL) cholesterol 114 vs. 110 mg/dl, P  < 0.001; mean triglycerides 136 vs. 125 mg/dl, P  < 0.001; mean high-density lipoprotein (HDL) cholesterol 47 vs. 48 mg/dl, P  = 006], and an excess of mortality (↑264%, P  = 0.006) due in great part not only to COVID-19 but also to other causes. CONCLUSION: In our setting, COVID-19 epidemics was associated with an increase in some prevalent sexually transmitted infections, with less but more advanced HIV infections, and with worse nonvirologic healthcare outcomes and higher mortality in people living with HIV.

Immunological and virological efficacy of different antiretroviral regimens initiated during acute/recent HIV infection.

OBJECTIVES: Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection. DESIGN: Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection. METHODS: We compared regimens based on protease-inhibitors (N = 28), integrase-strand-transfer-inhibitors (InSTI, N = 87) and nonnucleoside-reverse-transcriptase-inhibitors (N = 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 T-cell count >900 cells/µl and CD4/CD8 ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared. RESULTS: Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in all ART regimens and, InSTI group, comparable for dolutegravir and elvitegravir within InSTIs. CD4 T-cell counts at 1 year were comparable in all ART regimens. Overall proportion of patients reaching CD4 cell count more than 900 cells/µl and CD4/CD8 ratio more than 1 was 36% and 40% and 46% and 63% at 1 and 3 years, respectively with no differences among ART regimens. Starting ART during the earliest Fiebig stages (I-V vs. VI) was associated with higher rates of CD4 cell count more than 900 cells/µl at 3 years (P = 0.027). Discontinuation due to adverse events was more frequent with nonnucleoside-reverse-transcriptase-inhibitors compared with other ART classes. CONCLUSION: Viral suppression and immunological recovery were excellent, with no differences between ART regimens. Earlier ART initiation was associated with a higher proportion of long-term immunological recovery.

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.

A maintenance 3-day-per-week schedule with the single tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate is effective and decreases sub-clinical toxicity.

BACKGROUND: Antiretroviral drugs contained in single tablet Atripla have pharmacokinetic properties that could allow for longer than once-daily dosing. We hypothesized that simplifying Atripla once daily to 3-day per week would be feasible, able to maintain viral suppression and less toxic. METHODS: Virologically suppressed (≥2 years) HIV+ adults on Atripla once daily, CD4 greater than 350 cells/µl at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their once-daily (OD) regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W) (A-TRI-WEEK pilot trial). Primary end-point was the proportion of patients free of treatment failure (noncompleter = failure) at 24 weeks. CD4 and CD8 cells, ultrasensitive HIV-1 RNA, Pittsburg Sleep Quality Index (PSQI), bone mineral density, plasma efavirenz levels, and fasting blood and urine chemistries were measured at baseline and 24 weeks. The study is registered at ClinicalTrials.gov, NCT01778413. RESULTS: Sixty-one patients were randomized. All patients in both arms remained free of treatment failure (estimated difference 0%; 95% confidence interval -14.1 to 14.1). Ultrasensitive plasma HIV-1 RNA below detection threshold showed no difference between arms (70% in the 3W arm vs. 71% in the OD arm, P = 0.933) at 24 weeks. Total cholesterol and femur T-score significantly increased, whereas PSQI, plasma efavirenz, albumin/creatinine and beta-2-microglobulin in urine significantly decreased in the 3W arm relative to OD arm. CONCLUSION: The A-TRI-WEEK study represents a proof of concept for the feasibility of three-day per week Atripla maintenance that should be further confirmed in a larger, well powered clinical trial.

Neurological involvement in patients with acute/recent HIV-1 infection. A case-control study.

Primary HIV-1 infection is a relevant period for its virological and epidemiological consequences. Most patients present a symptomatic disease that can be potentially serious, but neurological involvement during primary HIV-1 infection has been poorly studied. The aim of this study was to describe the characteristics and outcomes of primary HIV-1 infection patients presenting neurological symptoms and to compare them with primary HIV-1 infection patients without neurological involvement. Retrospective case-control study (1:3) comparing primary HIV-1 infection patients with and without neurological involvement enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016. Matching criteria included age (±10 years), gender, year of diagnosis (±4 years), and Fiebig stage. The conditional logit model was used for comparisons. Fourteen out of 463 patients (3.02%) enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016 presented neurological symptoms. 28.5% of cases presented as meningitis and 71.5% as meningoencephalitis. Cerebrospinal fluid showed non-specific findings, including pleocytosis with lymphocyte predominance and increased protein levels. All cases required hospitalisation, whereas only 19% of the controls did. No other pathogen was identified in any case, but five patients initiated empirically antimicrobial treatment for other aetiologies until diagnosis was confirmed. CD4/CD8 ratio was significantly lower (p = 0.039) and plasmatic viral load significantly higher in the case group, compared to controls (p = 0.028). Risk factors, HIV-1 tropism, subtype distribution, and prescribed ART regimens were comparable between cases and controls. After 6 months on ART, 92% of cases had undetectable viral load, similar to controls, and CD4/CD8 ratio became also comparable between groups. All cases recovered rapidly with ART and were discharged without sequels. Neurological involvement during primary HIV-1 infection is unusual but serious, always requiring hospitalisation. Diagnosis is difficult because of the wide range of symptoms and similarities with other viral aetiologies. Neurological manifestations during primary HIV-1 infection are associated with a lower CD4/CD8 ratio and with a higher viral load than controls. Immediate ART initiation and rapid viral load decrease are required, allowing complete clinical recovery.

Tolerability of integrase inhibitors in a real-life setting.

Background: Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. Aims: We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Methods: Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit. Major outcomes were early discontinuation (≤1 year) due to any reason and more specifically due to toxicity. Incidence was calculated as number of episodes per 1000 person-years. Risk factors for discontinuation were assessed by multivariate Cox models. Results: Early discontinuations due to any reason were 271 (raltegravir), 168 (elvitegravir) and 264 (dolutegravir) per 1000 patient-years ( P = 0.0821). Early discontinuations due to toxicity were 76 (raltegravir), 103 (elvitegravir) and 81 (dolutegravir) per 1000 patient-years ( P = 0.6792). Overall, the most common toxicities leading to discontinuation were neuropsychiatric, osteomuscular or digestive. Most frequent neuropsychiatric manifestations reported at discontinuation were insomnia, dizziness, headache and anxiety irrespective of the integrase inhibitor. Among discontinuations due to toxicity, neuropsychiatric effects were more common with dolutegravir than with raltegravir or elvitegravir ( P = 0.0046). Age (HR 1.04, 95% CI 1.02-1.07, P = 0.0007) was the only independent risk factor for early discontinuation due to toxicity. Conclusions: Discontinuations due to any reason tended to be less common with elvitegravir, but discontinuations due to toxicity did not differ among integrase inhibitors. Neuropsychiatric toxicity leading to drug discontinuation was more frequent with dolutegravir.

Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression.

OBJECTIVES: We reviewed the 24 week outcomes of HIV-infected patients from our hospital who had their ART switched to dolutegravir monotherapy on an individual clinical basis. METHODS: Retrospective hospital database assessment of virally suppressed patients in whom the treating physician had switched to 50 mg of dolutegravir once daily due to one or more of the following reasons: antiretroviral-related adverse effects; comorbidities; risk of interactions; or archived resistance. Patients had ≥24 weeks of follow-up. Population, virological and immunological responses and safety and tolerability are described. RESULTS: Thirty-three (22 on PIs, of whom 18 had ritonavir-boosted PI monotherapy) patients were identified: median (IQR) age of 56 (50-62) years, 55% women, median (IQR) of 19 (17-23) years of known HIV infection, 39% prior AIDS events, median (IQR) of 8 (4-13) years with undetectable plasma HIV-1 RNA and median (IQR) CD4 cell count of 596 (420-843) cells/mm(3). Twenty-five (76%) patients had antiretroviral-related adverse effects, 32 (97%) patients had comorbidities, 28 (85%) patients had risk of interactions and 16 (48%) patients had archived resistance. One patient with suboptimal adherence had low-level virological failure through weeks 4-24. HIV RNA genotypic resistance tests detected no integrase mutations at weeks 4 and 24, but 118R was detected in 7% of the integrated HIV DNA at 24 weeks. Patients had significant median decreases in triglycerides (-117 mg/dL), total cholesterol (-36 mg/dL), the total cholesterol/HDL cholesterol ratio (-0.7) and high-sensitivity C-reactive protein (-0.05 mg/dL) (P ≤ 0.007), although the Chronic Kidney Disease Epidemiology Collaboration equation also decreased (-7.1 mL/min) (P < 0.0001). CONCLUSIONS: These data suggest the efficacy of dolutegravir monotherapy as a maintenance strategy to be further confirmed in randomized clinical trials.

Pandemic influenza A(H1N1) outbreak among a group of medical students who traveled to the Dominican Republic.

BACKGROUND: From the beginning of the influenza pandemic until the time the outbreak described here was detected, 77,201 cases of pandemic influenza A(H1N1) with 332 deaths had been reported worldwide, mostly in the United States and Mexico. All of the cases reported in Spain until then had a recent history of travel to Mexico, the Dominican Republic, or Chile. We describe an outbreak of influenza among medical students who traveled from Spain to the Dominican Republic in June 2009. METHODS: We collected diagnostic samples and clinical histories from consenting medical students who had traveled to the Dominican Republic and from their household contacts after their return to Spain. RESULTS: Of 113 students on the trip, 62 (55%) developed symptoms; 39 (45%) of 86 students tested had laboratory evidence of influenza A(H1N1) infection. Most students developed symptoms either just before departure from the Dominican Republic or within days of returning to Spain. The estimated secondary attack rate of influenza-like illness among residential contacts of ill students after return to Spain was 2.1%. CONCLUSIONS: The attack rate of influenza A(H1N1) can vary widely depending on the circumstances of exposure. We report a high attack rate among a group of traveling medical students but a much lower secondary attack rate among their contacts after return from the trip. These findings may aid the development of recommendations to prevent influenza.

Influenza C virus surveillance during the first influenza A (H1N1) 2009 pandemic wave in Catalonia, Spain.

Although particular attention is paid to influenza A and B virus isolates during influenza surveillance, influenza C virus (FLUCV) coexisted during the first influenza A (H1N1) 2009 pandemic wave during the 2009-2010 season. From 27 April 2009 to 9 May 2010, 12 strains of FLUCV were detected in specimens collected from 1713 nonhospitalized patients with upper respiratory tract illness using a molecular method. Half of the patients with FLUCV infection were older than 14 years. The most frequent symptoms were cough and fever, similar to other viral respiratory infections. Phylogenetic analysis of the hemagglutinin-esterase gene revealed that the strains belonged to the C/Kanagawa/1/76-related and C/Sao Paulo/378/82-related lineages, demonstrating their co-circulation in Catalonia. In addition to regular virological surveillance that provides information about the incidence and the exact role of FLUCV in acute viral respiratory infections in the general population, the genetic lineage identification offers additional data for epidemiological purposes.

Clinical presentation and prognosis of the 2009 H1N1 influenza A infection in HIV-1-infected patients: a Spanish multicenter study.

OBJECTIVE: The aim of the study was to describe the clinical presentation and prognosis in HIV-1-infected patients with hospital admission and pandemic influenza A 2009 (H1N1) confirmed, and compare this data with those of a general population. DESIGN: : This is a prospective study in nature. METHODS: All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009(H1N1) virus infection by real-time reverse transcriptase PCR assay or culture from June 12 to November 10, 2009 were recruited and followed up until 1 month after discharge. In the HIV group risk factors for HIV infection, AIDS criteria, last CD4 cell count and viral load, and antiretroviral therapy and pneumococcal vaccines were collected. RESULTS: Five hundred and eighty-five patients were recruited, 26 with HIV-1 infection and 559 non-HIV. The HIV patients had a long-term well controlled infection with a median CD4 cell count 503 cells/µl and 84% with undetectable viral load, although more frequently they had chronic liver and chronic obstructive pulmonary disease. No significant differences were observed about reported symptoms and physical findings on hospital admission. About 50% of patients in both groups present radiological infiltrates and 30% present respiratory failures. Practically all the patients in both groups received influenza antiviral therapy and in each group 80% received antibacterial therapy. No differences were observed in clinical outcomes. CONCLUSION: In HIV patients, well controlled on HAART, the pandemic influenza virus AH1N1 had a similar clinical outcome and prognosis to that of non-HIV patients.

Analytic performance of the PENTRA 80 automated blood cell analyzer for the evaluation of normal and pathologic WBCs.

We evaluated performance of the ABX PENTRA 80 (ABX Diagnostics, Montpellier, France) hematology analyzer in enumerating the most frequent subsets of WBCs in peripheral blood, atypical lymphocytes (ALYs), and large immature cells (LICs) by comparing results with those obtained by manual microscopic counts, another hematology analyzer, and flow cytometric immunophenotyping. Identification and enumeration of neutrophils and lymphocytes with the PENTRA 80 showed high correlation with all 3 reference methods (R2 > or = 0.92 and R2 > or = 0.88, respectively); quantification of eosinophils showed good correlation with the other analyzer and flow cytometric immunophenotyping (R2 > or = 0.70); lower correlation coefficients were found for comparisons with conventional microscopy (R2 > or = 0.50). For monocytes, lower but acceptable correlation and agreement were found; marginal correlation was found for basophils. The PENTRA 80 also showed good performance in detecting LICs but was less effective for the identification of ALYs in relatively low frequencies in abnormal peripheral blood samples. We found good performance of the 5-part leukocyte differential analyses for the PENTRA 80, especially for enumeration of neutrophils, lymphocytes, eosinophils, and LICs.

Viral community-acquired pneumonia in nonimmunocompromised adults.

INTRODUCTION: Viral community-acquired pneumonia (CAP) has been poorly studied and clinically characterized. Using strict criteria for inclusion, we studied this type of infection in a large series of hospitalized adults with CAP. MATERIALS AND METHODS: All nonimmunocompromised adult patients with a diagnosis of CAP having paired serology for respiratory viruses (RVs) [338 patients] were prospectively included in the study from 1996 to 2001 at our 1,000-bed university teaching hospital, and subsequently were followed up. We compared patients with pure viral (PV), mixed viral (RV + bacteria), and pneumococcal CAP. RVs (ie, influenza, parainfluenza, respiratory syncytial virus, and adenovirus) were diagnosed by means of paired serology. RESULTS: Sixty-one of 338 patients (18%) with paired serology had an RV detected, and in 31 cases (9%) it was the only pathogen identified. Influenza was the most frequent virus detected (39 patients; 64%). Patients with chronic heart failure (CHF) had an increased risk of acquiring PV CAP (8 of 26 patients; 31%) when compared to a mixed viral/bacterial etiology (2 of 26 patients; 8%; p = 0.035) or CAP caused by Streptococcus pneumoniae (1 of 44 patients; 2%; p = 0.001). Multivariate analysis revealed that CHF (odds ratio [OR], 15.3; 95% confidence interval [CI], 1.4 to 163; p = 0.024) and the absence of expectoration (OR, 0.14; 95% CI, 0.04 to 0.6; p = 0.006) were associated with PV pneumonia compared to pneumococcal CAP. CONCLUSION: RVs are frequent etiologies of CAP (single or in combination with bacteria). Patients with CHF have an increased risk of acquiring a viral CAP.