The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, ...information in real-life cohorts is relatively scarce for first-line use.
A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL.
135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure M = F) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic.
In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris is an uncommon infection for which there is no optimal therapy. We describe a young, female patient who presented with extensive ...cutaneous and neurological involvement and who recovered after receiving prolonged treatment with miltefosine, fluconazole, and albendazole.
People living with human immunodeficiency virus have an increased risk of anal cancer.
The aim of this study is to estimate anal cancer incidence and related risk factors in a national cohort of ...HIV-infected patients.
Prospective multicentric cohort study.
Multicentric study including patients from the Spanish HIV Research Network.
We collected data from 16,274 HIV-infected treatment-naïve adults, recruited from January 2004 to November 2020.
The primary outcome measures of this study were incidence and prevalence of anal carcinoma. Secondary outcome measures included the associations between baseline and time-dependent covariables and the primary endpoint.
Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29/100,000 persons-year which was stable over the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), with a median age of 43 years (IQR: 35 - 51), 34.6% (9/26) < 35 years, more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16248; 15%) and had lower nadir CD4 cell counts (115 µL vs 303 µL). In multivariable analysis, men who have sex with men and patients with prior AIDS-defining illness had an 8.3-fold (95%CI: 1.9 - 36.3) and 2.7-fold (95%CI: 1.1 - 6.6) increased hazard ratio for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI: 41%- 22%).
Lack of information on some potential risk factors, screening and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period.
While the overall incidence in our study was low, there was a significant number of patients < 35 years old with anal cancer. In addition to age, other factors such as men who have sex with men and patients with severe immunosuppression (current or past) should be prioritized for anal cancer screening.
T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV ...progression, and its potential association with CD4 changes in treated and untreated infection.
96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 IQR: 31-60 months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.
Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).
Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Granulomatous amoebic encephalitis caused by free‐living amoebae is a rare condition that is difficult to diagnose and hard to treat, generally being fatal. Anti‐amoebic treatment is often delayed ...because clinical signs and symptoms may hide the probable causing agent misleading the appropriate diagnostic test. There are four genera of free‐living amoeba associated with human infection, Naegleria, Acanthamoeba sp., Balamuthia and Sappinia. Two boys were admitted with diagnosis of acute encephalitis. The history of having been in contact with swimming pools and rivers, supports the suspicion of an infection due to free‐living amoebae. In both cases a brain biopsy was done, the histology confirmed granulomatous amoebic encephalitis with the presence of amoebic trophozoites.
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•A lower COVID-19 mortality rate was observed in HIV patients.•Similar hospitalization and ICU admission rates were observed in HIV patients.•Age and comorbidities also represent the ...main poor COVID-19 prognostic factors in PLHIV.•HIV severity or type of antiretroviral treatment does not influence the COVID-19 outcome.
Information on how COVID-19 affects people living with HIV (PLHIV) remains scarce.
An observational study was conducted in four public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 were included and compared with COVID-19 patients without HIV infection.
Sixty-three patients with HIV infection and confirmed or suspected COVID-19 were analyzed. The median age was 46 years (IQR: 37–56 years), and 88.9% were men. The median duration of HIV infection was 10.8 years (IQR: 6.5–16.8 years), and 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever (66.1%), cough (66.1%) and dyspnea (46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease, and 32.3% were admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. A significant association was observed between age, arterial hypertension, overweight, and diabetes mellitus and the severity of COVID-19. No association was observed between HIV-related factors and the severity of COVID-19. The rate of COVID-19 in HIV-patients was 1.68%. Similar hospitalization (31.74% vs 32.57%) and ICU admission (3.17% vs 2%) rates were observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and a lower global mortality rate (3.17% vs 6.96%) were also observed.
Established poor prognostic factors for COVID-19 patients, such as age and comorbidities, remain the main determinants for PLHIV. Neither the HIV severity nor the type of ARV treatment seem to influence the outcome of COVID-19. Large prospective cohorts are needed in order to establish the differences between HIV-positive and HIV-negative patients.
Free-living Amoebae of
Acanthamoeba
genus include non-pathogenic and pathogenic strains that are currently classified in 18 different genotypes, T1–T18. In this study, a survey was carried out to ...evaluate the presence of
Acanthamoeba
strains in soil samples collected between 2012 and 2013 in Gran Canaria Island, Canary Islands, Spain. Samples were inoculated onto non-nutrient agar (NNA) plates and were checked for the presence of
Acanthamoeba
. Identification of
Acanthamoeba
strains was based on the morphology of the cyst and trophozoite forms. Subsequently, positive samples were cloned for their molecular characterization at the genotype level by sequencing the DF3 region located in the 18S rDNA gene of
Acanthamoeba
as previously described. Sequencing results revealed the presence of T2, T5 and T4 genotypes within the studied samples. To the best of our knowledge, this is the first report demonstrating the presence of
Acanthamoeba
in Gran Canaria Island and the first study at the genotype level in the Canary Islands.
In Chagas disease (ChD) caused by Trypanosoma cruzi, new biomarkers to predict chronic cardiac pathology are urgently needed. Previous studies in chagasic patients with mild symptomatology showed ...that antibodies against the immunodominant R3 epitope of sCha, a fragment of the human basic helix‐loop‐helix transcription factor like 5, correlated with cardiac pathology. To validate sCha as a biomarker and to understand the origin of anti‐sCha antibodies, we conducted a multicenter study with several cohorts of chagasic patients with severe cardiac symptomatology. We found that levels of antibodies against sCha discriminated the high risk of sudden death, indicating they could be useful for ChD prognosis. We investigated the origin of the antibodies and performed an alanine scan of the R3 epitope. We identified a minimal epitope MRQLD, and a BLAST search retrieved several T. cruzi antigens. Five of the hits had known or putative functions, of which phosphonopyruvate decarboxylase showed the highest cross‐reactivity with sCha, confirming the role of molecular mimicry in the development of anti‐sCha antibodies. Altogether, we demonstrate that the development of antibodies against sCha, which originated by molecular mimicry with T. cruzi antigens, could discriminate electrocardiographic alterations associated with a high risk of sudden death.
To validate sCha as a biomarker and to understand the origin of anti‐sCha antibodies, we conducted a multicenter study with several severe cardiac cohorts of patients. Our results allowed us to identify the origin of autoantibodies against sCha by a molecular mimicry mechanism between the immunodominant R3H5 epitope and the PPDC peptide, and even though their pathological role was not evaluated, they are without doubt good discriminating biomarkers of ECG alterations associated with a high risk of sudden death.
Mycobacterium gordonae is a nontuberculous mycobacterium found in diverse environments and is considered an opportunistic pathogen in immunocompromised patients. We report the draft genome sequence ...of a Mycobacterium gordonae strain isolated from a free-living amoeba found in a nosocomial environment in Lima, Peru.
Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been ...reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use.
Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use.
The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors).
Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK