Effects of Immunonutrition in Advanced Human Immunodeficiency Virus Disease: A Randomized Placebo-controlled Clinical Trial (Promaltia Study).

Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in human immunodeficiency virus (HIV)-infected subjects initiating antiretroviral therapy (ART) at advanced HIV disease remain unclear. Methods: This was a pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T cells/µL or AIDS were randomized to either daily PMT25341 (a mixture of synbiotics, omega-3/6 fatty acids and amino acids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and α and ß microbiota diversity. Results: Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221 ± 108 cells/µL and mean CD4/CD8 ratio of 0.26 ± 0.19. PMT25341 was well tolerated, without grade 3-4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in mean CD4+ T-cell count change (278 vs 250 cells/µL, P = .474) or CD4/CD8 ratio change (0.30 vs 0.32, P = .854). Similarly, we did not detect differences between treatment arms in secondary endpoints. Conclusions: In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the gut-associated lymphoid tissue and microbiota. Clinical Trials Registration: NCT00870363.

Alternative switching strategies based on regimens with a low genetic barrier: do clinicians have a choice nowadays?

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

Predictive factors of hepatitis C virus eradication after interferon-free therapy in HIV coinfection.

Real-life cohorts have shown that the effectiveness of all-oral, direct-acting antivirals (DAA) for HCV treatment is > 90%. We aimed to explore the predictive factors of DAA success in HIV coinfection. This is an observational prospective study within the cohort "VIH-DOC", Madrid, Spain. HIV/HCV-coinfected patients were included if they had been treated with DAAs between 9 January 2015 and 31 August 2016. The sustained virological response (SVR) was analysed in the intention-to-treat population. Binary logistic regression was used to study the impact of cirrhosis, anti-HCV therapy experience and the IL28B polymorphism on SVR, besides factors with a p value < 0.15 from the univariate analysis. DAA were prescribed to 423 patients. SVR was confirmed in 92.9%. The univariate analysis showed higher proportion of patients with SVR among those with DAA adherence ≥ 95% (difference + 10.3%, 95% CI 3.5-19.6) and a baseline CD4+ cell count ≥ 200/µL (difference + 14.7%, 95% CI 4.1-31.0). Logistic regression evinced that both DAA adherence and baseline CD4+ cell counts predicted the SVR (OR 3.9, 95% CI 1.8-8.8, and OR 5.2, 95% CI 1.9-13.9, respectively). Moreover, men who reported having sex with other men (MSM) were less likely to achieve SVR (OR 4.2, 95% CI 1.1-16.1). Among MSM, three of three patients without SVR were suspected to have experienced HCV reinfection. DAA for HCV in HIV-coinfected patients is highly effective. DAA adherence ≥ 95% and a baseline CD4+ count ≥ 200/µL predicted a higher probability of SVR. A lower rate of SVR was found in MSM, presumably due to a higher frequency of HCV reinfection.

HCV eradication with all-oral therapy in cirrhotic HIV-coinfected patients: an observational study of early changes in liver function and fibrosis tests.

INTRODUCTION: liver laboratory tests improve in hepatitis C virus (HCV)-monoinfected and cirrhotic patients who achieve HCV cure after interferon-free treatment. OBJECTIVE AND METHODS: this study evaluates the changes in those tests in human immunodeficiency virus (HIV)-positive subjects with an eradicated HCV-coinfection using direct-acting antivirals and with a pre-therapy liver stiffness ≥ 14.6 kPa or clinical data of cirrhosis. Serum albumin, bilirubin, creatinine, platelet count and international normalized ratio (INR) values were collected at baseline, week 4, at the end of treatment and 24 weeks after the end-of-treatment. Fibrosis-4 score (FIB4) and Model for End-stage Liver Disease (MELD) score values were calculated and liver stiffness was estimated by transient elastography at baseline and 24 weeks after the end-of-treatment. The means were compared with the Student's t test or the repeated measures ANOVA test. RESULTS: direct-acting antivirals were prescribed to 131 HIV/HCV-coinfected cirrhotic patients. A sustained virological response was confirmed in 120 cases. Albumin, bilirubin and platelet count values improved in the entire population 24 weeks after the end-of-treatment. INR and MELD score values decreased when patients with atazanavir and/or acenocoumarol were excluded and liver fibrosis tests significantly diminished. Nine patients developed liver decompensation and there were three deaths. CONCLUSION: in conclusion, HCV eradication was associated with a short-term improvement in biochemical liver function and fibrosis tests in HIV-coinfected patients with cirrhosis, although clinical events still occur.

[Clinico-epidemiological characteristics of HIV-positive immigrants: study of 371 cases]. / Características clínico-epidemiológicas de los pacientes inmigrantes con infección por el VIH: estudio de 371 casos.

INTRODUCTION: The number of HIV-positive immigrants have increased in Spain in the last few years, and now represent a significant proportion of the epidemic. Our objective is to describe the clinico-epidemiological characteristics of HIV-positive immigrants seen in a specialist unit in Madrid. MATERIAL AND METHODS: Retrospective study. Every patient born in a country other than Spain and attended an HIV Unit in Madrid between 1992 and 2009 was included. RESULTS: Of the 371 patients included, 53.1% were Latin Americans, 24.5% Sub-Saharan Africans, and 22.4% others), and 60% were males. Immigrants represented 0.3% of new patients in 1992 and rose to 49.2% in 2009. The principal reason for HIV testing had been pregnancy/delivery among women (32.7%) and having a category-B disease among men (17.4%). Sexual transmission accounted for 92% of patients. Tuberculosis was the principal AIDS-diagnosing illness. Respectively 90%, 7.7%, 60%, 26.7%, 96% and 95% of patients had an IgG for HAV, HCV, Toxoplasma, Treponema, CMV and VZV. VHB-Ags+: 5.4%; PPD+: 17%. At least one syphilis episode was recorded in 62% of the men who have sex with men (MSM). Prevalence of HLA-B5701 was 6%, 0.9% and 3.8% in Caucasians, Amerindians and Afro-Americans, respectively. CONCLUSIONS: Immigrants represent a significant proportion of new HIV-positive patients. It is a very heterogeneous group according to their clinical and epidemiological characteristics.

[Imported diseases by immigrants and travellers: results from the Cooperative Network for the study of Imported Diseases by Immigrants and Travellers +Redivi]. / Infecciones importadas por inmigrantes y viajeros: resultados de la Red Cooperativa para el estudio de las Enfermedades Importadas por Inmigrantes y Viajeros +Redivi.

INTRODUCTION: Imported diseases by travellers and immigrants are a priority in the prevention of emerging infectious diseases in the 21st century. There are international records on imported diseases, but no such records are available in Spain. MATERIAL AND METHODS: The cooperative network +Redivi was created in 2009 and consists of 11 national healthcare centres. +Redivi collects demographic data relating to travel/migration and infectious diseases in brief, computerised forms. RESULTS: From January 2009 to October 2011, we collected 4,570 patients and recorded the main demographic data (age, sex, presence of immunosuppression), travel data (destination, duration, time between the return trip and the consultation) and data regarding the migratory process (country of origin, time between the arrival in Spain and the first consultation), as well as preventive measures that have been taken (pre-travel advice, need for malaria chemoprophylaxis, drug that was used and whether it was correct), the reason for coming to the consultation, and final diagnoses of the travellers, immigrants and immigrants-travellers. Likewise, the most frequent diagnoses of asymptomatic patients who came for a check-up are described for each of the three groups. CONCLUSIONS: The +Redivi network allows us to identify and quantify the geographical origin and the type of patients affected, as well as time pattern of infections imported by migrants and travellers. Preliminary data show the significant presence of transmissible diseases and the potential reintroduction in Spain, as well as the importance of systematic screening in patients that came from tropical areas. The objective of +Redivi is to evaluate the impact of imported diseases in Spain in order to contribute to improving the care of patients, to have an influence on prevention and treatment of the most prevalent imported diseases, and to detect possible outbreaks.

Greater acceptance of routine HIV testing (opt-out) by patients attending an infectious disease unit in Spain.

OBJECTIVE: Our objective was to determine attitudes and opinions of patients seen in our ID Unit on conducting HIV testing universally. METHODS: The survey was conducted in patients between 18 and 65 years without known HIV infection. Requested information about the test was previous embodiment, reasons for rejection, opinion on the universal realization, benefits and/or drawbacks, possible test performance, and availability of results "test negative stigma." RESULTS: We surveyed 91 patients (54.9% males). Surprisingly, up to 18.7% of patients mistakenly believed that HIV testing is routinely performed without consent. A great majority (98.9%) felt that universal performance on the test would benefit mainly in early diagnosing and/or preventing transmission. Patients younger than 42 years were significantly more prone to doing the test as a routine procedure. Only 4 (4.4%) patients did not participate because they believed they were "not infected." A vast majority (80.5%) of respondents would prefer to have results within the first 24 hours. In addition, 20.7% would have a problem with confidentiality if HIV serology testing was done. CONCLUSIONS: In summary, the vast majority (95.6%) of the surveyed patients had a fair opinion about universal HIV testing. Only 4 patients (4.4%) would not consent to HIV testing (because of low-risk perception). Availability of rapid HIV tests can facilitate fast result delivery, facilitating linkage to care. Considering favorable patients' opinion, recent opt-out screening recommendations, highest HIV prevalence in admitted patients, and cost-effectiveness, studies favor universal HIV testing.

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients.

Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.

Sustained virological response at week 12 after interferon-free therapy as criterion for HCV cure definition: Validation in a real-life cohort of HIV-coinfected patients.

INTRODUCTION: Sustained virological response (SVR) 12 weeks after the end-of-therapy (EOT) has been correlated with SVR24 for HCV-monoinfection. We aim to validate SVR12 as criterion for definition of HCV cure in HIV-coinfected patients treated with all-oral direct-acting antivirals (DAA). METHODS: Prospectively observational study including HIV/HCV-coinfected subjects who received DAA and had HCV-RNA measures at weeks 12 and 24 after EOT. Every patient who took ≥1 drug dose was analyzed. RESULTS: DAA were prescribed to 423 patients, of whom 387 had HCV-RNA measures both at weeks 12 and 24 after EOT. SVR12 was confirmed in 379/387 patients, while SVR24 was confirmed in 377/387 subjects. The positive-predictive-value (PPV) of SVR12 for SVR24 was 99.5% (95%CI: 98.1-99.9). One of the recurrences was clinically suspected to be a late relapse. CONCLUSIONS: SVR12 has a high PPV for HCV cure in HIV/HCV-coinfection, though further follow-up could be necessary for those with deeper immunosuppression.

Health care issues affecting transgender people living with HIV: an opportunity for improvement.

The high vulnerability of transgender (TG) persons to HIV infection and the difficulties associated with access to health services can lead to delays in the diagnosis and treatment of HIV infection, thus increasing the risk of transmission of HIV by this population. We performed a retrospective study to analyze the main characteristics of TG living with HIV infection in a hospital in Madrid, Spain and to identify issues related to lack of access to the health care system and combination antiretroviral therapy (cART). We analyzed 28 TG, of whom 22 (78.6%) were TG women. Median age was 28 years (interquartile range [IQR]: 29-45), 24 (85.7%) were Latin American (all of them without health insurance), and 12 (42.8%) were sex workers. Accessibility to the health system was more difficult for 22 (78.6%) of foreign-born TG people living with HIV, with a median delay to initiation of cART of six months (IQR: 2-24). These values were greater than those recorded for the control group comprising other people living with HIV (16.9% and one month, respectively). At the first access to health care in our hospital, CD4+ cell count and HIV viral load (VL) were worse in TG patients, with a median baseline CD4+ cell count below 350 cells/µl and a higher median HIV VL, both in naïve patients (28.6%) and in pre-treated patients whose therapy was interrupted owing to access-related issues (46.4%). These data show high vulnerability to HIV infection among TG and highlight that issues associated with access to health care can cause delays in the diagnosis and treatment of HIV infection. Based on our results, we think that the health care system should adapt to the sociodemographic, clinical, and behavioral characteristics of TG people living with HIV and develop specific, targeted preventive programs to address the vulnerability of this group.

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study.

BACKGROUND: Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN: Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS: We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. RESULTS: The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/µL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9-24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. CONCLUSIONS: Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

Should we look for Strongyloides stercoralis in foreign-born HIV-infected persons?

The objective was to evaluate the implementation of a systematic Strongyloides stercoralis screening programme in HIV infected immigrants attending an HIV Unit in Spain. An enzyme-linked immunosorbent assay (ELISA) was performed to assess the presence of Strongyloides IgG. Patients with a positive serology were treated with ivermectin; serologic follow-up testing was performed. 237 patients were screened (65.4 % men). Origin: 64.1 % came from Latin America, 16.5 % from Sub-Saharan Africa, 9.7 % from the Caribbean, 9.7 % from other areas. Strongyloides stercolaris IgG was positive in 13 cases (5.5 %). In the multivariate analysis, factors associated with a positive Strongyloides serology were illiteracy (OR: 23.31; p = 0.009) and eosinophilia (OR: 15.44; p < 0.0001). Nine of the 13 patients positive for S. stercoralis IgG and treated with ivermectin had a follow up serologic test: 77.8 % achieved a serologic response (55.5 % seroreversion). Screening of HIV-positive immigrants may be desirable, at least in those with higher risk of hyperinfection syndrome. Serologic testing seems a useful tool in both diagnosis and follow-up of these patients.

Boosted protease inhibitor monotherapy. What have we learnt after seven years of research?

Boosted protease inhibitor monotherapy has emerged as an antiretroviral alternative option to avoid the use of nucleosides. After more than seven years of research with hundreds of patients exposed to this kind of therapy, controversy about its use remains. While European and Spanish guidelines for the use of antiretroviral therapy in adults include monotherapy as an alternative for simplification, experts in the USA express the view that this strategy cannot be currently recommended. Our conclusion, after more than seven years of research, is that simplification of a suppressive triple antiretroviral therapy to boosted protease inhibitor monotherapy has demonstrated safety and efficacy in a high proportion of patients. Although this is not a strategy to implement indiscriminately in all patients, it could be a good option for those patients with toxicity related to nucleoside reverse transcriptase inhibitors, or for trying to avoid such toxicities in virologically controlled patients without previous failure to protease inhibitors, restarting nucleosides if the viral load does not remain undetectable. If simplification to monotherapy is selected to treat some patients, twice-daily lopinavir/ritonavir, or preferably once-daily darunavir/ritonavir, should be chosen as data with other boosted protease inhibitors are inconclusive or even nonexistent. Nevertheless, more studies focusing on the control of HIV replication in viral reservoirs with monotherapy, as with triple therapy, are warranted.