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Background: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo., Methods: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models., Results: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers., Conclusions: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract., (© 2024. The Author(s).)

Introduction: HIV continues to represent a problem of great relevance for public health in Spain. This study aims to carry out an analysis that will provide in-depth knowledge of the resources, clinical care, and management during the diagnosis, follow-up, and treatment phases of HIV infection in Spain., Methods: In the first phase, a multidisciplinary Scientific Committee designed an information collection tool in the form of a survey. In the second phase, carried out in the autonomous communities of Andalusia, Catalonia, and La Rioja, a multidisciplinary group of 42 experts, representatives of the public administration, clinical profiles, and representatives of NGOs in the field of HIV answered the survey., Results: The assessment of HIV resources is generally positive. As regards diagnosis, the experts considered that there was good coordination between Primary and Hospital care. Regarding treatment, the evaluations reflected good opinions on therapeutic conciliation and adherence, with a negative opinion in the evaluation of drug interactions with antiretroviral treatment. Regarding follow-up, the perception expressed was disparate concerning the coordination between Hospital and Primary Care as well as the adaptation of care to chronicity, aging, fragility, mental health, and oncological processes., Conclusion: There are certain processes that can be improved in the management of HIV infection in people with HIV in Spain, including protocols for follow-up and coordination between primary and hospital care in the treatment and follow-up of the disease., (Copyright © 2022 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors., Methods: We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004-2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors., Results: Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use., Conclusion: Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population., (© 2023. The Author(s).)

While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.

While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome-bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans , and Candida parapsilosis . In PWH, Candida and Pichia species were strongly correlated with several bacterial genera, including Faecalibacterium genus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candida species and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Background: Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions., Methodology: Cross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas., Results: We included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688)., Conclusion: In HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.

A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by a greater CD8 + T-cell decline., (Copyright © 2017 American Society for Microbiology.)

Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Introduction: The entry into force of Royal Decree (RD) 16/2012 in Spain in September 2012 led to the exclusion of the group of irregular immigrants from the National Healthcare System. With this work, GESIDA attempts to measure the impact of the entry into force of the RD in relation to its application by the Autonomous Communities (CCAA), and how it has affected the health care of irregular immigrants infected with HIV., Methods: Information was requested from the 17 CCAA of the existence of measures to ensure the care and treatment of people with HIV infection that were left unprotected because of the implementation of the RD. Likewise, a survey was conducted on health professionals and NGOs involved in the care of these people, to find out how it has affected the implementation of the RD to their daily healthcare work and the availability of information on regulations to implement it., Results: The response of the CCAA was variable, hardly contributing, in some cases, to mitigate the negative effect of the RD. To this is added a complex bureaucracy to access the benefits offered by some regions, often inaccessible to the most vulnerable subjects. Lack of information for health-care professionals and NGOs involved in the care of immigrants, hinders access of this population to health care and the establishment of control measures for diseases with an impact on the public health., Conclusions: The RD 16/2012 has had a negative impact on daily healthcare working, generating the appearance of deep inequities throughout the country., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background: Immigrant women living with HIV generally have worse adherence to medical treatment and follow-up when compared to native women and immigrant or native men. The general aim of this study was to improve healthcare services for HIV-positive women and to better understand why some of them discontinue treatment. The specific objectives were: (1) to explore the barriers and facilitators to medical follow-up among women and (2) to use the findings to create a guide for healthcare professionals with strategies and tools to encourage the immigrant women to continue with their healthcare treatment., Methods: We conducted a qualitative, patient-centred research based on semi-structured interviews in order to understand the drivers and barriers for HIV positive immigrant women to adhere to medical follow-up. A total of 26 women in active or discontinued treatment (from sub-Saharan Africa (10), Latin America (8) and Spain (8)) were interviewed in 2012 using a purposive sampling methodology. The semi-structured interviews were transcribed and analysed based on the grounded theory approach and the framework method. Three researchers took part in the triangulation of results.The study was approved by the Ethical Committee of the Hospital Universitario Ramón y Cajal., Results: The study revealed eight categories that impacted adherence to treatment and medical follow-up: doctor-patient relationship, relationship between body and HIV, employment, gender roles, representations of AIDS, emotional support received, trust in biomedical system, and psychological condition. Specific barriers and facilitators related to these categories were identified. In immigrant women, the influence of these barriers was greater than in Spanish women.Recommendations for healthcare professionals based on this study have been compiled in an informative brochure., Conclusions: Social, cultural, and psychological aspects as well as self-perception of body changes, gender roles, and the relationship with the healthcare system, are key elements that may affect the adherence to medical treatment of immigrant women living with HIV.Qualitative research focused on the comprehensive experience of living with HIV can be useful for creating tools that pave the way to detect barriers and facilitators to medical follow-up in specific populations.

Objectives: We aimed to evaluate whether virological response to a short course of maraviroc monotherapy could predict HIV-1 tropism., Methods: A clinical trial was performed in HIV-1 treatment-naive patients infected with R5- or non-R5-tropic virus determined using the Trofile(®) assay, with >1000 HIV-1 RNA copies/mL. Maraviroc was administered for 10 days. Viral load was measured at baseline and days 4, 7, 10 and 28. The main outcome measurement was the decline in HIV-1 RNA at day 10. The trial was registered in the ClinicalTrials.gov database (NCT01060618; TROPISMVC)., Results: Forty patients [30 R5 and 10 dual/mixed (D/M)] were recruited. There was a significant decrease in HIV-1 RNA after 10 days of maraviroc treatment in patients with R5-tropic virus (median 1.52 log10 RNA copies/mL; 95% CI 1.23-1.63; P < 0.0001), but also in patients with D/M-tropic virus (median 1.62 log(10) RNA copies/mL; 95% CI 0.33-1.88; P = 0.00024). The difference in the HIV-1 RNA decrease (-0.16 log(10) RNA copies/mL; 95% CI -0.53 to 0.22) was not significant (P = 0.410). A decrease >0.5 log(10) RNA copies/mL was found in 96.3% of patients with R5-tropic virus and in 70% of patients with D/M-tropic virus (P = 0.052). The differences were not significant when a decline of 1 log(10) RNA copies/mL was considered (92.6% versus 70%; P = 0.11)., Conclusions: Treatment-naive patients infected with R5- or D/M-tropic virus have similar virological responses to a short course of maraviroc monotherapy. This clinical test thus cannot be used as a surrogate marker of viral tropism in this population., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose of the Review: Chagas disease has spread beyond the geographical barriers of the American continent in the past decade. Consequently, physicians treating HIV-infected patients in nonendemic countries have to face an opportunistic infection they have little experience with. This review examines the literature on Chagas disease in HIV-infected patients, with special emphasis on recent findings., Recent Findings: Although infection by Trypanosoma cruzi is a severe opportunistic infection in HIV-infected patients, awareness of this parasitosis in nonendemic countries remains low. Deeply immunosuppressed patients with chronic infection can develop reactivations, which can be very severe and are associated with high mortality. Reactivations mostly affect the central nervous system, followed by the heart, and diagnosis is based on the direct detection of the parasite or histology. There is no reliable method of predicting reactivations. Treatment is based on benzimidazoles, although neither the appropriate treatment schedule nor the need for secondary prophylaxis has been clearly established. Antiretroviral therapy seems to play a fundamental role in the prevention of reactivations and control of relapses; however, more information is needed., Summary: Many aspects of T. cruzi-HIV coinfection remain uncertain. Until new data covering the current gaps become available, early diagnosis and prompt antiretroviral therapy seem to be fundamental for avoiding reactivations and improving late visceral involvement.

The immigrant population in Spain, whether legal or not, has been entitled to healthcare under the same conditions as the Spanish population since the year 2000. The entry into vigour of the Royal Decree-Law 12/2012 of 20 April has significantly restricted this right, so that unauthorized or non-resident foreigners may now only receive emergency care, if they are under 18 or pregnant women. Out of an estimated 459,909 illegal immigrants in our country, 2,700 to 4,600 are probably infected with HIV; 1,800 to 3,220 know that they are infected, and 80% of the latter could receive antiretroviral treatment. The Royal Decree-Law is likely to cause many undesirable consequences in this population infected with HIV: increasing mortality, promoting the emergence of opportunistic diseases, increasing hospital admissions, increasing infections in the population (by HIV and other pathogens), or contributing to mother to child transmission of HIV. The expected increase in morbidity and mortality will be a greater cost in patient care, a cost which will be significantly higher in the more immunosuppressed patients. Therefore, the enforcement of the Royal Decree-Law will be much less cost-effective in the short term than was expected, and will negatively affect our country's public health, especially for those patients infected with HIV who will not be covered, thus increasing healthcare medium to long term costs, and moving away from the international health goals that were established., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Background: We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART., Methods: The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan-Meier analysis and Cox regression., Results: We followed 1,090 patients, of whom 318 were women (45.6% immigrant women [IW]). At initiation of treatment, women had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7 vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF between women and men was not significantly different (hazard ratio [HR], 1.10; 95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that of Spanish-born women (25.5% vs 11.6%)., Conclusions: Although response to cART was similar for both sexes, men started treatment later. IW were more frequently lost to follow-up and switched treatment. Measures to improve medical follow-up after initiation of cART should be promoted among this minority group.

Background: Initiation of highly active antiretroviral therapy (HAART) with low CD4 lymphocyte counts is associated with AIDS-related and non-AIDS-related events and increased mortality. However, no clear association has been found with an increased rate of treatment failure., Methods: We conducted a meta-analysis including randomized clinical trials of currently recommended HAART in naive patients to evaluate treatment response in very late starters (VLSs). Studies with information on response in at least one of the two strata (≤ 50 versus >50 CD4 cells/mm(3) and/or ≤ 200 versus >200 CD4 cells/mm(3)) and follow-up of at least 48 weeks were analysed. A pooled odds ratio of the effect of starting HAART with ≤ 50 versus >50 or ≤ 200 versus >200 CD4 cells/mm(3) for each arm by fitting a random-effect logistic regression model was computed. Sources of heterogeneity [sex, age, year of study initiation, nucleos(-t)ide pair and third drug] were investigated., Results: We included 25 treatment arms from 13 randomized clinical trials. Being a VLS consistently impairs treatment outcomes at 48 and 96 weeks. Only hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection was associated with a reduced impact of late initiation of HAART; at 48 weeks for 50 and 200 cells/mm(3) thresholds (P = 0.013 and P = 0.032, respectively). None of the remaining sources of heterogeneity explored was significantly associated with the impact of being a VLS., Conclusions: We found that initiation of antiretroviral therapy with very low CD4 lymphocyte counts is consistently associated with poorer outcomes of HAART. This effect could be modulated by HBV/HCV coinfection, but not by the individual components of the HAART regimen.

As a result of population migration, Chagas disease is no longer limited to the North and South American continents. In HIV-infected patients, chronic infection by Trypanosoma cruzi behaves as an opportunistic infection in severely immunosuppressed patients and is responsible for high morbidity and mortality. Unlike other opportunistic infections, information on the natural history, diagnosis, treatment, and prevention of Chagas disease is scarce. Spain has the highest number of cases of Chagas disease outside the North and South American continents, and coinfection with HIV is increasingly prevalent. In this article, the Spanish Society for Tropical Medicine and International Health (Sociedad Española de Medicina Tropical y Salud Internacional) reviews the current situation of coinfection with HIV and T. cruzi infection and provides guidelines on the diagnosis, treatment, and prevention in areas where Chagas disease is not endemic. It also identifies areas of uncertainty where additional research is necessary.

Objective: currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment., Methods: historical multicenter cohort study of naïve patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders., Results: a total of 1090 treatment-naïve HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs. 39 y), more frequently female (37.5% vs. 24.6%), with less HCV coinfection than autochthonous patients (7% vs. 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs. 4.98 Log(10)), CD4 lymphocyte count (193.5/µL vs. 201.5/µL), late initiation of HAART (56.4% vs. 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs. 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF., Conclusions: the response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy.

Background: Migration is a growing phenomenon with a well-known impact in infectious diseases epidemiology. Currently, immigrants represent almost 10% of the Spanish population. The majority come from countries where the prevalence of chronic viral illnesses is higher than in Spain., Methods: To describe clinicoepidemiological features of human immunodeficiency virus (HIV)-infected immigrants attending our Unit and to compare differential characteristics depending on geographical origin, information from all new immigrants from January 1997 to December 2006 was collected., Study Design: noninterventional retrospective chart review., Results: We screened 1,609 patients of whom 77 (4.8%) were HIV antibody (Ab) positive. Of these, 80% were sub-Saharan Africans (SSAFR) and 20% were South-Central Americans (SCA). HIV prevalence was higher in SSAFR (5.6% vs 3.2%; p= 0.04). Overall, of those who were HIV Ab positive, 70% were male (median age 30 years), 59% heterosexuals, 9% hepatitis C virus coinfected, 8.6% hepatitis B virus coinfected, and 34% showed a positive tuberculin skin test. Median CD4 cell count was 263 cells/microL, median HIV-ribonucleic acid viral load 4.6 Log/mL, and 48% had a late diagnosis [acquired immunodeficiency syndrome (AIDS)-defining illness or <200 CD4 microL at the time of diagnosis]. Only 68% of patients for whom antiretroviral therapy was indicated actually started therapy and 22% were lost to follow-up just after diagnosis. SCA had lower CD4 cell counts (26 vs 168 cells/microL; p= 0.016), higher viral loads (5.3 vs 4.8 Log; p= 0.001), and were more likely to have an AIDS-defining illness (53% vs 21%; p= 0.04) compared to SSAFR. Tuberculin skin test reactivity was more common among SSAFR versus SCA [adjusted by CD4 count, odds ratio (OR) 6.3 and 95% confidence interval (CI): 0.65-60.5]. The main risk factor for late diagnosis was geographical origin: OR 4.6 (95% CI: 1.11-19.3) (SCA vs SSAFR; adjusted by the interval between the date of arrival in Spain and the date of HIV diagnosis)., Conclusions: Almost half the HIV-infected immigrants were diagnosed in late stages. Patients were frequently lost to follow-up, and a significant minority did not start highly active antiretroviral therapy when indicated. SCA seem to have more severe immunosuppression at the time of diagnosis than SSAFR. Early voluntary routine HIV screening should be promoted.

Introduction: Adherence is essential for successful antiretroviral therapy (ART), but complex dosing schedules compromise the adherence to and efficacy of this treatment. Once-daily (QD) ART simplifies treatment by lowering the dosing frequency and pill burden. The aim of this study, performed when QD regimens were still limited, was to determine the degree of adherence and patient satisfaction of QD dosing versus twice-daily dosing (BID) of ART., Methods: Non-interventional, multicenter, longitudinal study, including initial (I), simplification (S), and rescue (R) therapies. Medical visits were performed at baseline, and at 3 and 6 months. A validated, structured questionnaire was used to assess adherence, and a visual analogical scale applied by independent observers was used to assess satisfaction., Results: From May to December 2002, 978 patients were recruited. Average pill burden was 5 in QD vs. 6.1 in BID regimens. Undetectable viral load was achieved at 6 months in 83.7% (I), 87.5% (S), and 57.4% (R) of patients, with no significant differences between QD and BID. Adherence and satisfaction with ART were both significantly better in QD vs. BID regimens: 61.4% vs. 53.2% (P < .05) and 54.4% vs. 41.2% (P < .05), respectively. Multivariate analysis revealed the following variables to account for 1) Adherence to ART (OR; 95% CI): treatment satisfaction (1.53, 1.30-1.80), family support (1.25, 0.98-1.61), years of HIV infection (0.97, 0.94-1.003) and intravenous drug use (0.83, 0.70-0.99); 2) Satisfaction with ART: simplification group (1.70, 1.22-2.34), QD therapy (1.33, 1.13-1.56), years of HIV infection (0.95, 0.93-0.98), and CDC stage C (0.85, 0.73-1.01); and 3) Undetectable viral load: naive group (5.08, 3.14-8.22) and adherence (1.57, 1.13-2.17)., Conclusion: QD antiretroviral schedules appear to be as effective as BID regimens, with better adherence and treatment satisfaction. This may positively affect treatment efficacy at long-term.

Purpose: To evaluate the incidence and severity of adverse events (AEs) and treatment interruption (TI) with efavirenz in a population with a high rate of intravenous drug use (IVDU)., Method: This was a national, multicenter, and observational study of HIV-infected adult patients who were starting an efavirenz-containing regimen. Evaluations of AEs were made in routine clinical practice at baseline and at least 3 months later. A total of 1,033 patients were included from 60 participating hospitals; 20% were antiretroviral naive. The risk factor for HIV infection was IVDU in 62.3%, and 6.6% of participants were on methadone., Results: AEs affected 29.3% of participants, and treatment was interrupted in 8.23%. The most frequent AEs were CNS disturbances that affected 24.1% participants; these AEs were considered related to efavirenz in 18.5% patients. AEs were not severe, and treatment had to be interrupted in 6% of patients. Other AEs were cutaneous rash (incidence of 5.9%; 2.4% of TI), gastrointestinal disturbances (1.45%; no TI), and elevation of liver function test (0.68%; no TI). Patients taking methadone had more AEs (39.7%), mainly CNS disturbances, and TI (19.1%). Cutaneous rash was more frequent among women. Psychoactive drug consumption, previous history of psychiatric disorders, antiretroviral experience, or previous nevirapine intolerance were not associated with higher incidence of AEs., Conclusion: Safety and tolerance of efavirenz is good in most patients, even in a population with a high rate of IVDU. The most common AEs are CNS disturbances; they are not severe and rarely lead to TI.

Purpose: To identify particular characteristics of HIV+ patients from correctional facilities (CF) compared with an HIV+ population from the community to better detect variables for intervention., Method: In our hospital, HIV+ patients are admitted to an infectious diseases ward (IDW) when they come from the community or to a penitentiary unit (PU) when they are transferred from CF. We retrospectively reviewed admissions of those patients in both areas during 1999., Results: Admissions of HIV+ patients to IDW and PU generate 2.3% and 53.4% of hospital and PU stays, respectively. Both populations were equivalent in terms of mean age, CD4 count, viral load, prophylaxis for opportunistic infections, average stay, and death during stay. Male sex (91% vs. 74%), previous or current intravenous drug use (88% vs. 77%), and hepatitis C virus (HCV) seropositivity (97% vs. 82.6%) were more frequent in the PU than in the IDW. Multivariate analysis identified three factors as being independently related to admission from prison: longer time of known HIV infection (average 3.3 years; 95% CI 1.9-4.6), no previous antiretroviral treatment (odds ratio [OR] 2.95; 95% CI 1.46-6.0), and admission due to tuberculosis (OR 2.5; 95% CI 1.03-6.0)., Conclusion: HIV infection is still a serious medical problem in CF. Although imprisonment can provide access to health programs, HIV-infected prison patients suffer more frequently from tuberculosis and take less antiretroviral treatment.

Background: Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment.Methods: We present the 96 week results of a neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96.Results: The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS [week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471] were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90).Conclusions: Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed. [ABSTRACT FROM AUTHOR]

Miltefosine, liposomal amphotericin B, cutaneous leishmaniasis, post-kala-azar dermal leishmaniasis, diabetes mellitus Keywords: Miltefosine; liposomal amphotericin B; cutaneous leishmaniasis; post-kala-azar dermal leishmaniasis; diabetes mellitus EN Miltefosine liposomal amphotericin B cutaneous leishmaniasis post-kala-azar dermal leishmaniasis diabetes mellitus 1 2 2 11/09/22 20221001 NES 221001 A 65-year-old Nigerian man presented in May 2018 with a cutaneous lesion on the left ear that developed in January 2018. [Extracted from the article]

Background: A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events. Methods: Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts. Results: We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duration) confirmed the independent association of a low CD4/CD8 ratio with the risk of non-AIDS morbidity (per CD4/CD8 ratio quartile decrease, OR, 2.9; 95% CI, 1.3–6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5–5.3). Conclusions: The CD4/CD8 ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients. [ABSTRACT FROM AUTHOR]

Background: The prevalence of transmitted HIV drug resistance (TDR) is stabilizing or decreasing in developed countries. However, this trend is not specifically evaluated among immigrants from regions without well-implemented antiretroviral strategies. Methods: TDR trends during 1996-2010 were analyzed among naïve HIV-infected patients in Spain, considering their origin and other factors. TDR mutations were defined according to the World Health Organization list. Results: Pol sequence was available for 732 HIV-infected patients: 292 native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA) and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish, 8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased from 11.3% in 2004-2006 to 8.4% in 2007-2010. Characteristics related to a decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI-resistance, HIV-1 subtype B, male sex and infection through injection drug use. TDR remained stable for PI-resistance, in patients infected through sexual intercourse and in those carrying non-B variants. However, TDR increased among SSA and females. K103N was the predominant mutation in all groups and periods. Conclusion: TDR prevalence tended to decrease among HIV-infected native Spanish and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants in 2007-2010. These results highlight the importance of a specific TDR surveillance among immigrants to prevent future therapeutic failures, especially when administering NNRTIs. [ABSTRACT FROM AUTHOR]

Background. The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. Methods. We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log[sub10] or ⩾5.0 log[sub10]copies/mL. The primary end point was the percentage of tients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. Results. Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log[sup10] copies/mL, and median CD4[sup+] cell count was 208 cells/μL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the COM/EFV arm and 26 patients (14%) in the ddI/3TC/EFV arm discontinued the study medication because of adverse events (Pp.046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (Pp.003). Conclusions. At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity. Clinical trials registration. NCT00256828. [ABSTRACT FROM AUTHOR]