Sífilis maligna, una presentación de sífilis a tener en cuenta / Syphilis Maligna: A Presentation to Bear in Mind

La sífilis maligna es una forma infrecuente de sífilis secundaria asociada a la infección por el VIH, caracterizada clínicamente por nódulos necróticos y lesiones ulceradas generalizadas. Presentamos 4 pacientes diagnosticados de sífilis maligna tras revisar los casos de sífilis diagnosticados en nuestro centro entre 2012 y 2016. Describimos los aspectos epidemiológicos, clínicos, histopatológicos y serológicos, así como su relación con el VIH y la respuesta al tratamiento. Aunque se trate de una forma de sífilis poco frecuente, en los últimos años ha aumentado el número de casos publicados, principalmente pacientes jóvenes infectados por el VIH. Es necesario incluir la sífilis maligna en el diagnóstico diferencial de pacientes infectados por el VIH con lesiones ulceradas y necróticas

Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions

Syphilis Maligna: A Presentation to Bear in Mind. / Sífilis maligna, una presentación de sífilis a tener en cuenta.

Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions.

Epidemiological changes of acute/recent human immunodeficiency virus type 1 infection in Barcelona, Spain (1997-2015): a prospective cohort study.

OBJECTIVE: To describe the epidemiology of acute/recent human immunodeficiency virus (HIV) infection over two decades in Barcelona (Spain). METHODS: Prospective, single-centre cohort including all patients with an acute/recent HIV infection (<180 days) since 1997. Patients were stratified into four periods. Phylogenetic analysis was performed to determine clusters of transmission. RESULTS: A total of 346 consecutive acute/recently infected patients were included. The annual proportion of recent infections among total new HIV diagnoses increased over time from 1% (29 out of 1964) to 8% (112 out of 1474) (p <0.001). Proportion of men who have sex with men (MSM) in the cohort increased from 62% (18 out of 29) to 89% (100 out of 112) (p <0.001). The proportion of migrants showed a non-significant increasing trend (24% (7 of 29) to 40% (45 of 112)) likewise the non-B subtype (0% to 22% (22 of 112)). The mean time from infection to diagnosis was 53.6 days (interquartile range (IQR) 50-57), comparable among all periods. Mean time from infection to treatment decreased over the years from 575 (IQR 467-683) to 471 (IQR 394-549) days (p <0.001) without significant differences between migrants and non-migrants (133 (IQR 71-411) versus 208 (IQR 90-523) days p 0.089). Almost 50% (152 of 311) of recently infected individuals were included in a cluster of transmission, and 92% (137 of 149) of them were MSM. CONCLUSION: The MSM population has progressively grown within acutely/recently infected patients in Barcelona, and is frequently involved in transmission clusters. Although the time between diagnosis and treatment has been reduced, the time between infection and diagnosis still needs to be shortened.

Sexual acquisition of HIV infection after solid organ transplantation: Late presentation and potentially fatal complications.

INTRODUCTION: While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV-infection after transplantation through sexual route, the primary mode of transmission in the general population. METHODS: From two different centers, we report nine new cases of HIV infection in SOT recipients attributed to sexual acquisition: eight cases of kidney-transplant recipients and one heart-transplant recipient. FINDINGS: There were nine cases of post-transplant HIV-infection detected among 14 526 transplants performed 1998 to 2015. In 6/9 cases, infection was contracted 5 years after SOT. All but one patient had stable allograft function under immunosuppressive therapy. The main trigger to diagnosis was late CMV disease and sexually transmitted diseases; five patients had CDC-stage 3 HIV infection. In 7/9 patients, virologic response and CD4 recovery were achieved within 3 months after starting antiretroviral therapy (ART). After an average of 3.6 years post diagnosis, 5/9 patients remained alive with well-controlled infection and functioning allograft. CONCLUSION: Sexual acquisition of HIV infection after SOT represents a difficult challenge, as it may occur in any kind of transplant and at any time. The course of infection resembles that of the general population, with life-threatening infectious complications, but good response to ART. Assessment of lifestyle and risk behavior is paramount, as indications may be not disclosed without direct questioning.

Estimation of renal function by CKD-EPI versus MDRD in a cohort of HIV-infected patients: a cross-sectional analysis.

BACKGROUND: Accurately determining renal function is essential for clinical management of HIV patients. Classically, it has been evaluated by estimating glomerular filtration rate (eGFR) with the MDRD-equation, but today there is evidence that the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has greater diagnostic accuracy. To date, however, little information exists on patients with HIV-infection. This study aimed to evaluate eGFR by CKD-EPI vs. MDRD equations and to stratify renal function according to KDIGO guidelines. METHODS: Cross-sectional, single center study including adult patients with HIV-infection. RESULTS: Four thousand five hundred three patients with HIV-infection (864 women; 19%) were examined. Median age was 45 years (IQR 37-52), and median baseline creatinine was 0.93 mg/dL (IQR 0.82-1.05). A similar distribution of absolute measures of eGFR was found using both formulas (p = 0.548). Baseline median eGFR was 95.2 and 90.4 mL/min/1.73 m2 for CKD-EPI and MDRD equations (p < 0.001), respectively. Of the 4503 measurements, 4109 (91.2%) agreed, with a kappa index of 0.803. MDRD classified 7.3% of patients as "mild reduced GFR" who were classified as "normal function" with CKD-EPI. Using CKD-EPI, it was possible to identify "normal function" (>90 mL/min/1.73 m2) in 73% patients and "mild reduced GFR" (60-89 mL/min/1.73 m2) in 24.3% of the patients, formerly classified as >60 mL/min/1.73 m2 with MDRD. CONCLUSIONS: There was good correlation between CKD-EPI and MDRD. Estimating renal function using CKD-EPI equation allowed better staging of renal function and should be considered the method of choice. CKD-EPI identified a significant proportion of patients (24%) with mild reduced GFR (60-89 mL/min/1.73 m2).

Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.

OBJECTIVES: The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection. METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing. RESULTS: Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions. CONCLUSIONS: Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection.

UNLABELLED: A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel of six recombinant viruses from five different subtypes (M. Medina-Ramirez et al., J Virol 85:5804-5813, 2011, http://dx.doi.org/10.1128/JVI.02482-10). Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The neutralization breadth was positively associated with time postinfection (P = 0.0001), but contrary to what has been reported for chronic infections, no association with the viral load was observed. Notably, five individuals within the first 6 months of infection (two as early as 77 and 96 days postinfection) showed substantial cross-neutralization. This was confirmed with an extended panel of 20 Env pseudoviruses from four different subtypes (two in tier 3, 14 in tier 2, and four in tier 1). Sera from these individuals were capable of neutralizing viruses from four different subtypes with a geometric mean 50% infective dose (ID50) between 100 and 800. These results indicate that induction of cross-neutralizing responses, albeit rare, is achievable even within 6 months of HIV-1 infection. These observations encourage the search for immunogens able to elicit this kind of response in preventive HIV-1 vaccine approaches. IMPORTANCE: There are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier than previously thought. The identification of HIV-1-infected patients with these activities within the first months of infection and characterization of these responses will help in defining new immunogen designs and neutralization targets for vaccine-mediated induction of bNAbs.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort.

In this prospective, multicentre cohort study, we analysed specific prognostic factors and the impact of timing of highly active antiretroviral therapy (HAART) on disease progression and death among 625 human immunodeficiency virus (HIV)-1-infected, treatment-naïve patients diagnosed with an AIDS-defining disease. HAART was classified as early (<30 days) or late (30-270 days). Deferring HAART was significantly associated with faster progression to a new AIDS-defining event/death overall (p 0.009) and in patients with Pneumocystis jiroveci pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio 1.83; 95% CI 1.25-2.68). Other independent risk factors for poorer outcome were baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4(+) count (<50 cells/µL).

Liver retransplantation in HIV-infected patients: a prospective cohort study.

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Simultaneous pancreas-kidney transplantation in HIV-infected patients: a case report and literature review.

Since the introduction of combined antiretroviral therapy (cART), solid organ transplantation (SOT) has become a therapeutic option for the HIV-positive population. In contrast with liver and kidney transplantation, only three simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV-infected patients. Herein we have reported the first SPKT in an HIV-infected patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9 months because of a Pseudomonas aeruginosa infection. The three recipients reported in the literature lived, despite the failure of both the pancreas and kidney grafts in one subject. Despite the poor outcome of our case, HIV-1 infection was controlled after transplantation (stable CD4(+) cells and no AIDS-related events), and the kidney graft functioned with no episodes of rejection. The cART regimen used in the pretransplant period was switched at the time of transplantation to raltegravir and two nucleoside reverse transcriptase inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs. Target plasma levels of tacrolimus were achieved at a dose similar to that used in HIV-negative transplant recipients. The most adequate antiretroviral regimen for HIV-infected SOT recipients has not yet been established; however, one may consider switching protease inhibitors or non-NRTI-based regimens for a raltegravir-based regimen at the time of transplantation.

Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation.

BACKGROUND: Cidofovir (CDV) is a nucleotide analogue with broad antiviral activity. This drug has a very favorable pharmacokinetic profile that enables intermittent dosing, but the potential for nephrotoxicity has hitherto restricted its use in stem cell transplant recipients. Data on pediatric patients are limited. OBJECTIVES: To report the efficacy and toxicity of CDV in a group of pediatric patients with cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation. STUDY DESIGN: Prospective evaluation of safety and efficacy of CDV used pre-emptively for CMV reactivation in 10 out of 30 children who underwent allogeneic hematopoietic stem cell transplantation from January 2000 to December 2001. In all the patients but one, CDV was used as second-line therapy (after foscarnet or ganciclovir) of CMV reactivation. RESULTS: Overall, 12 courses of CDV were administered with a median 5 doses per course, range 1-6 (two patients were treated twice). Considering the first CDV treatment episode, 8 out of 10 patients had positive CMV antigenemia assay when they started CDV. Five of eight antigenemic patients responded completely while three were switched to foscarnet or ganciclovir, respectively, due to increasing (one) or persistent CMV antigenemia (two). Overall, the therapy with CDV was well tolerated, but it was withdrawn in one patient due to a two-fold increase in the baseline creatinine level. This patient concurrently had a high tacrolimus blood level. CONCLUSION: Safety is the major concern regarding the use of CDV but the adoption of probenicid, intravenous hydration and anti-emetic therapy improved its tolerability profile. Our data suggest that CDV has an acceptable toxicity and would deserve further controlled studies in the setting of pre-emptive therapy for CMV.