Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial.

BACKGROUND: Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV. METHODS: SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing. FINDINGS: 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline characteristics were similar; median age was 37 years (range 18-74), 118 (18%) of 670 were female sex at birth, 207 (31%) of 670 were non-White, and median BMI was 25·9 kg/m2 (IQR 23·3-29·5). At month 11-12, long-acting cabotegravir plus rilpivirine showed non-inferior efficacy versus bictegravir, emtricitabine, and tenofovir alafenamide (HIV-1 RNA ≥50 copies per mL, five [1%] of 447 vs one [<1%] of 223), with an adjusted treatment difference of 0·7 (95% CI -0·7 to 2·0). Excluding injection site reactions, adverse events and serious adverse events were similar between groups. No treatment-related deaths occurred. More long-acting group participants had adverse events leading to withdrawal (25 [6%] of 454 vs two [1%] of 227). Injection site reactions were reported by 316 (70%) of 454 long-acting participants; most (98%) were grade 1 or 2. INTERPRETATION: These data support the use of long-acting cabotegravir plus rilpivirine dosed every 2 months as a complete antiretroviral regimen that has similar efficacy to a commonly used integrase strand transfer inhibitor-based first-line regimen, while addressing unmet psychosocial issues associated with daily oral treatment. FUNDING: ViiV Healthcare.

Decay of HIV RNA in Seminal Plasma and Rectal Fluid in Treatment-Naive Adults Starting Antiretroviral Therapy With Dolutegravir Plus Lamivudine or Bictegravir/Emtricitabine/Tenofovir Alafenamide.

BACKGROUND: Decay of HIV in seminal plasma (SP) and rectal fluid (RF) has not yet been described for the antiretroviral combination of dolutegravir (DTG) + lamivudine (3TC). METHODS: In this randomized multicenter pilot trial, males who were antiretroviral naive were randomized (2:1) to DTG + 3TC or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). HIV-1 RNA was measured in blood plasma (BP), SP, and RF at baseline; days 3, 7, 14, and 28; and weeks 12 and 24. RESULTS: Of 25 individuals enrolled, 24 completed the study (DTG + 3TC, n = 16; BIC/FTC/TAF, n = 8). No significant differences were observed between groups for median decline in HIV-1 RNA from baseline at each time point or median time to achieve HIV-1 RNA <20 copies/mL in BP and SP and <20 copies/swab in RF. HIV-1 RNA decay patterns were compared in individuals receiving DTG + 3TC. Despite significantly higher percentages for changes from baseline in BP, median (IQR) times to HIV-1 RNA suppression were shorter in SP (7 days; 0-8.75) and RF (10.5 days; 3-17.5) than in BP (28 days; 14-84; P < .001). CONCLUSIONS: Comparable HIV-1 RNA decay in BP, SP, and RF was observed between DTG + 3TC and BIC/FTC/TAF. As shown with triple-drug integrase inhibitor-based regimens, rapid HIV-1 RNA suppression in SP and RF is achieved with DTG + 3TC, despite decay patterns differing from those of BP. CLINICAL TRIALS REGISTRATION: EudraCT 2019-004109-28.

Characteristics and Outcomes by Ceiling of Care of Subjects Hospitalized with COVID-19 During Four Waves of the Pandemic in a Metropolitan Area: A Multicenter Cohort Study.

INTRODUCTION: The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia. METHODS: Observational study conducted during the first (March-April 2020), second (October-November 2020), third (January-February 2021), and fourth wave (July-August 2021) of COVID-19 in five centers of Catalonia. All subjects were adults (> 18 years old) hospitalized with a proven SARS-CoV-2 infection and with therapeutic ceiling of care assessed by the attending physician at hospital admission. RESULTS: A total of 5813 subjects were analyzed. Subjects with a ceiling of care were mainly older (difference in median age of 20 years), with more comorbidities (Charlson index 3 points higher) and with fewer clinical signs at baseline than patients without a ceiling of care. Some features of their clinical profiles changed among waves. There were differences in treatments received during hospital admission across waves, but not between subjects with and without a ceiling of care. Subjects with a ceiling of care had a death incidence more than four times the death incidence of subjects a without a ceiling of care (risk ratio (RR) ranging from 3.5 in the first wave to almost 6 in the third and fourth). Incidence of severe pneumonia and complications for subjects with a ceiling of care was around 1.5 times the incidence in subjects without a ceiling of care. DISCUSSION: Analysis of hospitalized subjects with SARS-CoV-2 infection should be stratified according to therapeutic ceiling of care to avoid bias and outcome misestimation.

Quantification and Progress Over Time of Specific Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 in Breast Milk of Lactating Women Vaccinated With BNT162b2 Pfizer-BioNTech Coronavirus Disease 2019 Vaccine (LacCOVID).

Background: Several observational studies demonstrated the passage of postvaccine antibodies through breast milk in women vaccinated against coronavirus disease 2019 (COVID-19), mostly with messenger RNA (mRNA)-based vaccines, but lacked long-term data. Methods: A 6-month prospective cohort study was performed to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced antibody levels in the breast milk of 33 lactating healthcare workers at different timepoints after mRNA BNT162b2 Pfizer-BioNTech COVID-19 vaccination. Moreover, we examined the correlation of SARS-CoV-2 antibody levels between serum and breast milk, adverse events related to vaccination, and rate of SARS-CoV-2 infections. Results: Mothers' median age was 38 (interquartile range [IQR], 36-39) years and 15 (IQR, 10-22) months for infants. Median (IQR) SARS-CoV-2 immunoglobulin G (IgG) spike protein subunit S1 (S1) vaccine-induced levels at different timepoints for serum-milk pairs were 519 (234-937) to 1 (0-2.9) arbitrary units (AU)/mL at 2 weeks after first dose and 18 644 (9923-29 264) to 78 (33.7-128), 12 478 (6870-20 801) to 50.4 (24.3-104), 4094 (2413-8480) to 19.9 (10.8-51.9), 1350 (831-2298) to 8.9 (7.8-31.5) AU/mL at 2, 4, 12 and 24 weeks after second dose, respectively. We observed a positive correlation of antibody levels between serum and breast milk, no serious adverse events related to vaccination, and 2 (6%) COVID-19 vaccine breakthrough infections. Conclusions: Women vaccinated with Pfizer-BioNTech transmit antibodies into breast milk with a positive correlation with serum levels. Both decreased over time in a 6-month follow-up.

Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study).

Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicentre study (BACTCOVID).

OBJECTIVES: The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. METHODS: We performed a severity matched case-control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. RESULTS: Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9-20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65-4.07; p < 0.001). DISCUSSION: Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk.

Global Perspectives on Immunization Against SARS-CoV-2 During Pregnancy and Priorities for Future Research: An International Consensus Paper From the World Association of Infectious Diseases and Immunological Disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis.

BACKGROUND: Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered. METHODS: In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005-2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded. RESULTS: We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a "missed" PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%). CONCLUSIONS: During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

Lower Success Rate of Débridement and Implant Retention in Late Acute versus Early Acute Periprosthetic Joint Infection Caused by Staphylococcus spp. Results from a Matched Cohort Study.

BACKGROUND: Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed. QUESTIONS/PURPOSES: (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure? METHODS: In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy. RESULTS: Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001). CONCLUSIONS: Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

Timing of implant-removal in late acute periprosthetic joint infection: A multicenter observational study.

OBJECTIVES: We evaluated the treatment outcome in late acute (LA) periprosthetic joint infections (PJI) treated with debridement and implant retention (DAIR) versus implant removal. METHODS: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy. LA PJI was defined as acute symptoms <3 weeks in patients more than 3 months after the index surgery and with a history of normal joint function. RESULTS: 445 patients were included, comprising 340 cases treated with DAIR and 105 cases treated with implant removal (19% one-stage revision (n = 20), 74.3% two-stage revision (n = 78) and 6.7% definitive implant removal (n = 7). Overall failure in patients treated with DAIR was 45.0% (153/340) compared to 24.8% (26/105) for implant removal (p < 0.001). Difference in failure rate remained after 1:1 propensity-score matching. A preoperative CRIME80-score ≥3 (OR 2.9), PJI caused by S. aureus (OR 1.8) and implant retention (OR 3.1) were independent predictors for failure in the multivariate analysis. CONCLUSION: DAIR is a viable surgical treatment for most patients with LA PJI, but implant removal should be considered in a subset of patients, especially in those with a CRIME80-score ≥3.

Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention.

OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described. METHODS: Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: (i) the need for implant removal, (ii) infection related death, (iii) the need for suppressive antibiotic therapy and/or (iv) relapse or reinfection during follow-up. RESULTS: 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35). CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection.

Virological Outcome Measures During Analytical Treatment Interruptions in Chronic HIV-1-Infected Patients.

BACKGROUND: Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies. METHODS: We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated. RESULTS: The set point was lower than baseline VL (median delta set point, -0.26; P < .001). This difference was >1 log10 copies/mL in 13.9% of the cases. The median TtR was 2 weeks; no patients had an undetectable VL at week 12. The median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions. CONCLUSIONS: TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

Correction: Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization.

[This corrects the article DOI: 10.1371/journal.pone.0186602.].

Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization.

BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. RESULTS: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. CONCLUSIONS: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923610.

Current outcomes and predictors of treatment failure in patients with surgical site infection after elective colorectal surgery. A multicentre prospective cohort study.

OBJECTIVE: To determine current outcomes and predictors of treatment failure among patients with surgical site infection (SSI) after colorectal surgery. METHODS: A multicentre observational prospective cohort study of adults undergoing elective colorectal surgery in 10 Spanish hospitals (2011-2014). Treatment failure was defined as persistence of signs/symptoms of SSI or death at 30 days post-surgery. RESULTS: Of 3701 patients, 669 (18.1%) developed SSI; 336 (9.1%) were organ-space infections. Among patients with organ-space SSI, 81.2% required source control: 60.4% reoperation and 20.8% percutaneous/transrectal drainage. Overall treatment failure rate was 21.7%: 9% in incisional SSIs and 34.2% in organ-space SSIs (p < 0.001). Median length of stay was 15 days (IQR 9-22) for incisional SSIs and 24 days (IQR 17-35) for organ-space SSIs (p < 0.001). One hundred and twenty-seven patients (19%) required readmission and 35 patients died (5.2%). Risk factors for treatment failure among patients with organ-space SSI were age ≥65 years (OR 1.83, 95% CI: 1.07-1.83), laparoscopy (OR 1.7, 95% CI: 1.06-2.77), and reoperation (OR 2.8, 95% CI: 1.7-4.6). CONCLUSIONS: Rates of SSI and treatment failure in organ-space SSI after elective colorectal surgery are notably high. Careful attention should be paid to older patients with previous laparoscopy requiring reoperation for organ-space SSI, so that treatment failure can be identified early.

Predictive Factors for HIV Seroconversion Among Individuals Attending a Specialized Center After an HIV Risk Exposure: A Case-Control Study.

OBJECTIVE: To better target our current prevention strategies, we assessed factors associated with HIV seroconversion in individuals attending a specialized center after a risk exposure. MATERIALS AND METHODS: We studied individuals from an HIV Unit's contact risk cohort at a tertiary care hospital in Barcelona, Spain, between 2003 and 2013 and performed a retrospective matched case-control study. Cases were individuals who seroconverted to HIV after at least 3 months since first follow-up visit for a contracting risk. Controls were HIV-negative individuals from the same cohort. Demographics and behavior variables were studied and compared using a McNemar test assessing factors associated with seroconversion. Univariate analysis and binary logistic regression were performed to develop a model for predicting probability of HIV seroconversion. We also evaluated sensitivity and specificity of our model and an area under Receiver Operating Characteristic (ROC) curve was estimated. RESULTS: Sixty-nine (2.2%) individuals seroconverted after a median (interquartile range) of 24 (9-34) months since last follow-up. Seroconverters were predominantly male (96%) and men who have sex with men (MSM) (94%). No differences were observed regarding risk of exposure. Being MSM [odds ratio (OR) 5.2 (1.4-20.2), p = .01], having a known HIV-positive partner [OR 2.7 (1.2-6.2), p = .02], previous postexposure prophylaxis (PEP) [OR 3.9 (1.0-15.6), p = .05], and having previous sexually transmitted infections (STIs) [OR 4.6 (1.9-10.9), p = .001] were the factors independently associated with HIV seroconversion. The sensitivity and specificity of our model were 64.06% and 73.53%, respectively, and the area under ROC curve was 0.777. DISCUSSION: HIV seroconversions were observed frequently between individuals attending a specialized center because of a risk exposure. Being MSM, having had previous PEP, an HIV-positive sexual partner, and previous STI were predictive factors for HIV seroconversion. Closer and longer follow-up and/or pre-exposure prophylaxis should be considered to prevent HIV infections in this high-risk population.

Post-exposure prophylaxis for HIV infection: a clinical trial comparing lopinavir/ritonavir versus atazanavir each with zidovudine/lamivudine.

BACKGROUND: A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed. METHODS: A total of 255 individuals attending the emergency rooms of six hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up. Secondary end points were incidence of side effects, follow-up at days 90 and 180 and rate of seroconversions. RESULTS: A total of 55 patients (29 in lopinavir/ritonavir and 26 in atazanavir arms) did not attend the first scheduled appointment (day 1) and were excluded from the analysis. The rate of discontinuation before day 28 owing to any cause was similar between groups (37/102 [36%] in lopinavir/ritonavir and 35/98 [36%] in atazanavir arms, P=0.82). Adverse events were the reason for discontinuation or switching of PEP in 33 individuals (16/102 [16%] in the lopinavir/ritonavir arm and 17/98 [17%] in the atazanavir arm, P=0.84). Adverse events were reported in 92/200 (46%) of individuals on PEP who attend at least the day 1 appointment (50/102 [49%] in the lopinavir/ritonavir arm and 42/98 [43%] in the atazanavir arm, P=0.38). There were no seroconversions. CONCLUSIONS: The rate of discontinuation of PEP before day 28 was similar with zidovudine/lamivudine plus either lopinavir/ritonavir or atazanavir. The rate of discontinuation of PEP because of adverse events was low in both arms. Almost 50% of the patients of both arms suffered side effects. New strategies are needed to improve the tolerance.

Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02).

BACKGROUND: To investigate the safety and immunogenicity of a modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B), a phase-I, doubled-blind placebo-controlled trial was performed. METHODS: 30 HIV-uninfected volunteers at low risk of HIV-1 infection were randomly allocated to receive 3 intramuscular injections (1×10(8)pfu/dose) of MVA-B (n=24) or placebo (n=6) at weeks 0, 4 and 16. All volunteers were followed 48 weeks. Primary end-points were adverse events and immunogenicity. RESULTS: A total of 169 adverse events were reported, 164 of grade 1-2, and 5 of grade 3 (none related to vaccination). Overall 75% of the volunteers showed positive ELISPOT responses at any time point. The magnitude (median) of the total responses induced was 288SFC/10(6)PBMC at week 18. Antibody responses against Env were observed in 95% and 72% of vaccinees at week 18 and 48, respectively. HIV-1 neutralizing antibodies were detected in 33% of volunteers. CONCLUSIONS: MVA-B was safe, well tolerated and elicited strong and durable T-cell and antibody responses in 75% and 95% of volunteers, respectively. These data support further exploration of MVA-B as an HIV-1 vaccine candidate. Clinical Trials.gov identifier: NCT00679497.