Alfonso Cabello

Peripheral T follicular helper Cells Make a Difference in HIV Reservoir Size between Elite Controllers and Patients on Successful cART

HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group differences were tested using non-parametric tests. Compared with the TX patients, the EC patients had smaller HIV reservoir not only in Trm but also in pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh cells harbored similar levels of HIV-DNA in the EC (p = 0.60) and TX patients (p = 0.17); however, the contribution to HIV-DNA levels in memory CD4+ T-cells varied among the pTfh and non-pTfh subsets in both groups of patients. The EC patients showed smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a population of cells with a pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection in pTfh cells and the ability of the EC patients to spontaneously control HIV replication.

The use of steroids to prevent cutaneous reactions to benznidazole in patients with Chagas disease.

Abstract The treatment of Chagas disease is limited by the frequent cutaneous side effects of benznidazole. We tested the use of steroids plus escalating doses of benznidazole to prevent this complication in 17 adult patients with chronic Trypanosoma cruzi infection and found extremely good tolerance. A randomized trial is warranted.

HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells.

Background There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. Patients and methods Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. Results HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. Conclusions We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

Tinea nigra palmaris: a clinical case in a rural Ethiopian hospital

ABSTRACT Tinea nigra is an infrequent, superficial fungal infection, mainly caused by Hortaea werneckii, which is still underreported in Ethiopia. An asymptomatic 62-year-old male patient sought a rural hospital of Ethiopia, showing dark plaques on the palms of both hands. A superficial mycosis was suspected and a direct light microscopic mycological examination from skin scrapings revealed short brownish hyphae. To our knowledge, this is the first case of tinea nigra from the Ethiopian highlands. This may be due to the actual rarity of the condition or to underreporting.

Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia

INTRODUCTION Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. MATERIAL AND METHODS The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 - 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. RESULTS In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. CONCLUSIONS Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

Long-Term Efficacy of Nevirapine Plus Co-Formulated Abacavir/ Lamividune as Simplification Therapy in HIV-Infected Patients with Undetectable Viral Load

Background: The long-term efficacy of NVP+ABC+3TC as a simplification strategy for the treatment of HIV-1 infected patients with undetectable viral load has not been properly assessed in randomized trials. This low-cost treatment with limited renal and bone side effects must be of particular interest in this era of cost-containment urgency and also in limited resource settings. Methods: Observational study of 232 HIV1-infected patients with undetectable viral load who initiated nevirapine (NVP) + abacavir (ABC) + lamivudine (3TC). Reasons for the switching were treatment simplification (56%), renal problems (6%), osteopenia/osteoporosis (7%), hyperlipidemia (11%) and others (20%). HIV-1 viral load, CD4 cell count and fasting biochemistry profiles were determined on a routine clinical practice. The aim of the study was to evaluate long-term efficacy of this combination and its effect on renal function and lipid metabolism. Results: 232 patients had a mean follow-up of 4 years (712 patients-year). The mean increment of CD4 after 4 years was 83 cells/μL (13% from baseline). Viral load remained undetectable in all but 14 patients (6%). Triglycerides levels decreased by 10% overtime (p < 0,05). 25 patients (10,7%) stopped therapy due to NVP associated side effects; no ABC associated side-effects were observed. No changes were found in renal function or bone mineral density. Conclusions: The combination of NVP+ABC+3TC is a safe option for maintaining longterm viral suppression and immunological control, preserving renal function and improving hypertriglyceridemia.

Fiebre entérica en Madrid. Una revisión de los últimos 30 años

BACKGROUND Our aim is analyze the epidemiological factors of enteric fever in Madrid (Spain) over the last 30 years. MATERIAL AND METHODS A retrospective review was conducted on cases of typhoid and paratyphoid fever studied in the Fundación Jiménez Díaz (Madrid) between 1980 and 2010. Two similar periods in time were studied (P1: 1980-1993; P2: 1994-2010). RESULTS There was a total of 61 confirmed cases of enteric fever: 51 (84%) were typhoid and 10 were paratyphoid: 45 patients were native Spanish (40 belonging to P1) and 16 were immigrants (15 in P2, with 11 of them coming from the Indian sub-continent). CONCLUSION Enteric fever must be present in the differential diagnosis of persistent fever without clear focus in immigrants, mainly from the Indian subcontinent, and travelers from endemic areas.