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Objectives: We assessed the opinions of physicians caring for people with HIV (PWH) from the multicentre Spanish CoRIS cohort regarding the assessment of health-related quality of life (HRQoL)., Methods: We designed an online self-administered questionnaire comprising 27 structured questions across four domains: (i) sociodemographic and clinical data; (ii) usefulness of measuring HRQoL; (iii) information, training and resource needed; and (iv) whether and how HRQoL should be measured. Physicians completed the questionnaire between April and June 2023., Results: Of 131 physicians surveyed [53.8% men, median age 52 years (interquartile range: 42-60)], 90.9% and 88.6% agreed that measuring HRQoL is useful for both PWH and medical decision-making, respectively. However, 67.2% needed training on what HRQoL is and how to measure it, 79.4% required information on validated tools, and 80.9% felt that clinical guidelines are needed. Overall, 90.1% of physicians agreed that HRQoL should be measured among PWH. Most physicians (82.8%) supported using specific scales for PWH, with 74.1% recommending annual measurement, 49.1% suggesting that nurses from HIV units conduct the assessments, and 43.1% favouring personal interviews during medical visits. At the time of the survey, 55.3% of physicians did not measure HRQoL in any patients due to time or resource constraints (75.8%)., Conclusions: Despite the recognized importance of HRQoL measurement in PWH, Spanish physicians encounter barriers such as time constraints and limited resources. Developing clear guidelines, using tailored scales, and integrating digital tools along with multidisciplinary support could enhance routine HRQoL assessments and improve patient-centred care., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/μL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/μL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens., Competing Interests: Potential conflicts of interest. J. A. P. M. reports consulting fees from Gilead Sciences and GSK; honoraria for advisory boards or public speaking from Gilead Sciences, GSK, and ViiV Healthcare; nonfinancial travel support from ViiV Healthcare and Gilead Sciences; and research grants from Gilead Sciences and ViiV Healthcare. S. M. reports participation on data and safety monitoring boards or advisory boards, speaking activities for which they received payment or honoraria, travel support, and grants for research from Gilead Sciences, Janssen Cilag, Merck Sharp & Dohme, and ViiV Healthcare. S. S. V. reports personal fees from ViiV Healthcare and Janssen Cilag; payment or honoraria from Gilead Sciences and MSD; consulting fees from Mikrobiomik and Aptatargets; nonfinancial travel and/or meeting support from ViiV Healthcare and Gilead Sciences; issued or pending patents for microbiome-associated biomarkers of anal cancer and severe acute respiratory syndrome coronavirus 2 susceptibility test in saliva; and research grants from MSD and Gilead Sciences. J. C. L. B. Q. reports consulting fees from ViiV Healthcare and MSD; honoraria for advice or public speaking from Gilead Sciences, MSD, Janssen Cilag, and ViiV Healthcare; and travel support and grants from ViiV Healthcare. J. B. reports consulting fees from Gilead Sciences, ViiV Healthcare, and GSK; honoraria for advice or public speaking from Gilead Sciences, GSK, Janssen Cilag, MSD, and ViiV Healthcare; travel support from MSD and ViiV Healthcare; and grants from Gilead Sciences, MSD, and ViiV Healthcare. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since SAR-COV-2 infection emerged and spread worldwide, little is known about its impact on people living with human immunodeficiency virus (HIV). We performed a single-center retrospective study to describe the potential particularities and risk factors for respiratory failure (RF) in that population. This single-center retrospective study included patients infected with HIV, whose current follow-up is run in this center, above18 years of age, with diagnosis of SARS-CoV-2 infection between March 5, 2020 and April 15, 2021. We collected data regarding HIV immunological and virological status, main epidemiological characteristics, as well as those conditions considered to potentially influence in SARS-CoV-2 evolution; and clinical, microbiological, radiological, respiratory status, and survival concerning coronavirus disease 2019 (COVID-19). We compared all that, for patients with and without RF and performed a logistic regression for suspected risk factors for RF. One hundred seventy-seven HIV patients were diagnosed from COVID-19 (mean age 53.8 years, 81.3% male). At diagnosis, 95.5% were receiving ART and 91.3% had undetectable viral load, with median CD4 count of 569 cells/μL. One hundred thirty-eight patients (78.4%) had symptoms, 44 (25%) developed RF and 53 (31%) developed bilateral pneumonia. The most commonly used treatments were: steroids (26.7%) and hydroxychloroquine (13.1%). When comparing patients with and without RF, we found statistically significant differences for 20 of the analyzed variables such as age ( p  < .001) and CD4 ( p 0.002), and route of HIV transmission by intravenous drug users IVDU ( p 0.002) were determined. In multivariate analysis, age [odds ratio (OR) 1.095] and CD4 count less than 350 cells/μL (OR 3.36) emerged as risk factor for RF. People living with HIV whose CD4 count is <350 cells are at higher risk of developing RF when infected by SARS-CoV-2.

Background: HIV infection has become a chronic disease and well-being of people living with HIV (PLHIV) is now of particular concern. The objectives of this paper were to describe self-rated health among PLHIV, on ART and on ART virally suppressed and to analyse its determinants., Methods: Data were obtained from a second-generation surveillance system based on a cross-sectional one-day survey in public hospitals. Epidemiological and clinical data were collected among HIV-infected inpatients and outpatients receiving HIV-related care the day of the survey in 86 hospitals in 2019. Self-rated health was measured using a question included in the National Health Survey: "In the last 12 months, how would you rate your health status?" an ordinal variable with five categories (very good, good, moderate, bad and very bad). For the analysis, these responses were dichotomized into two categories: 1 = very good/good and 0 = moderate, bad or very bad health status. Factors associated with very good/good self-rated health were estimated using logistic regression., Results: Of 800 PLHIV, 67.5% perceived their health as very good/good, 68.4% among PLHIV on ART and 71.7% of those virally suppressed. Having university education (adjusted odds ratio (aOR):2.1), being unemployed (aOR:0.3) or retired (aOR:0.2), ever being diagnosed of AIDS (aOR:0.6), comorbidities (aOR:0.3), less than 2 year since HIV diagnosis (aOR:0.3) and not receiving ART (aOR:0.3) were associated with good self-rated health. Moreover, among PLHIV on ART, viral load less than 200 copies (aOR:3.2) were related to better perceived health. Bad adherence was inversely associated with good self-rated health among PLHIV on ART (aOR:0.5) and of those virally suppressed (aOR:0.4)., Conclusions: Nearly seven in 10 PLHIV in Spain considered their health status as very good/good, being higher among virally suppressed PLHIV. Both demographic and clinical determinants affect quality of life.

People living with HIV-1 experience an accelerated aging due to the persistent and chronic activation of the immune system. This phenomenon conduces to immune exhaustion and precipitate immunosenescence. In general, frailty is defined as a syndrome of physiological degeneration in the elderly. Circulating naïve and memory T cells were studied by flow cytometry in non-frail and frail HIV-1-infected groups. Thymopoiesis, cell activation, senescence and cell proliferation were analyzed by CD31, HLA-DR/CD38, CD28/CD57 and Ki-67 expression, respectively. Plasma levels of sCD14 and MDA were measured by ELISA. Frail infected individuals showed a reduced number of memory T cells, both CD4+ and CD8+ populations. Activated CD3+CD4+HLA-DR+ T cells were lower in frail individuals, and directly correlated with CD3+CD8+HLA-DR+ and CD8M cells. Senescent CD8+CD28-CD57+ cells were reduced in frail HIV-1 infected individuals and inversely correlated with CD8RTE, CD8N and CD3+CD4+HLA-DR+. Higher plasma levels of sCD14 and MDA were found in HIV-1 infected frail individuals. Our data show association among frailty, markers of immune activation and oxidative stress. Understanding the immune mechanisms underlying frailty status in HIV-1 population is of high relevance not only for the prediction of continuing longevity but also for the identification of potential strategies for the elderly., Competing Interests: The authors have declared that no competing interests exist.

There are few studies comparing the safety and immunogenicity of the same HIV immunogen in healthy volunteers and HIV-infected individuals. We analyzed demographics, adverse events (AEs), and immunogenicity against vaccinia virus in preventive (RISVAC02, n = 24 low-risk HIV-negative volunteers) and therapeutic (RISVAC03, n = 20 successfully treated chronically HIV-1-infected individuals) vaccine phase-I clinical trials that were performed with the same design and the same immunogen (modified vaccinia virus Ankara-B: MVA-B). Total AEs were significantly higher in HIV-infected patients (mean AEs/patient 6.6 vs. 12.8 ( p < 0.01)). Conversely, the number of AEs related to vaccination (AEsRV) was similar between both groups. No grade III or IV AEsRV were observed in either clinical trial. Regarding the immunogenicity, the proportion of anti-vaccinia virus antibody responders was similar in both studies. Conversely, the magnitude of response was significantly higher in HIV-infected patients (median binding antibodies at w8 267 vs. 1600 U/mL ( p = 0.002) and at w18 666 vs. 3200 U/mL ( p = 0.003)). There was also a trend towards higher anti-vaccinia virus neutralizing activity in HIV-infected individuals (proportion of responders 37% vs. 63% ( p = 0.09); median IC50 32 vs. 64 ( p = 0.054)). This study confirms the safety of MVA-B independent of HIV serostatus. HIV-infected patients showed higher immune responses against vaccinia virus.

Background: Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies., Methods: We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated., Results: The set point was lower than baseline VL (median delta set point, -0.26; P < .001). This difference was >1 log10 copies/mL in 13.9% of the cases. The median TtR was 2 weeks; no patients had an undetectable VL at week 12. The median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions., Conclusions: TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives: HIV patients have seen accelerated ageing. Our objective was to determine the prevalence of frailty, to evaluate factors associated with frailty and to evaluate physical function in older HIV-infected adults., Design: this was a cross-sectional study., Setting: outpatient clinics of two public university hospitals in Madrid (Spain)., Methods: frailty was defined according to the criteria of Fried: shrinking, weakness, poor endurance and energy, slowness and low physical activity level, being frail those who met at least three criteria, prefrail one or two criteria and robust when they met no criteria. Physical function was assessed using standardised methods., Results: we evaluated 117 HIV-infected patients. Mean age was 61.3 ([standard deviation] 6.87) years. All patients were on antiretroviral therapy. Median current CD4+ T-cell count was 638 (144-1871) cells/μl, and median CD4/CD8 ratio was 0.79 (0.00-3.62). The prevalence of frailty was 15.4%, and that of prefrailty was 52.1%. In the multivariate analyses depressive symptoms (OR [95% CI], 9.20 [2.17-39.05]) and CD4/CD8 ratio (OR 0.11 [0.02-0.61]) were associated with frailty. Even though 100% of the patients were able to walk and perform basic activities of daily life independently, functional impairment was high (20% slow gait and 55% Short Physical Performance Battery ≤9)., Conclusions: HIV-infected patients aged ≥55 years have a high prevalence of frailty and a high burden of functional impairment. Optimal management of this population requires close collaboration between infectious diseases specialists and geriatricians., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Trial Design: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART., Methods: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination., Results: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses., Conclusion: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity., Trial Registration: ClinicalTrials.gov NCT01571466.

Objectives: The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed., Methods: HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466., Results: MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment., Conclusions: MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram., (© The Author 2015. 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.)

Objectives: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients., Methods: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48., Results: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events., Conclusions: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons., (© 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.)

Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4(+) T cell responses were predominantly Env directed, whereas the CD8(+) T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8(+) T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8(+) T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate.

Background: Pandemic 2009 influenza A/H1N1 (H1N1v) is resistant to adamantanes, leaving neuraminidase inhibitors as the only therapeutic option. Other mutations are considered to be associated with virulence and clinical severity. However, out of the surveillance programs, few studies analyze the presence of resistance/virulent H1N1v variants in certain clinical circumstances., Objectives: To define the frequency and role of resistance and virulence mutations in a specific clinical circumstance-in patients with persistent infection by H1N1v., Study Design: Observational study of patients with persistent H1N1v infection admitted to our hospital., Results: NAI-resistance mutations were detected in 14.3% of cases with persistent infection (2/14), and in none of the non-persistent controls (0/15). These cases were initially infected with susceptible variants that acquired resistance at different time-points after therapy with oseltamivir (OTV). The first case (case 2) was an HIV-positive patient who rapidly acquired resistance 9 days after diagnosis (6 days on OTV) and whose infection resolved after standard OTV therapy. The second case (case 3) was a patient with chronic lymphocytic leukemia [corrected] and the longest viral persistence (59 days). The resistance mutation was detected in the specimen taken on day 37 after diagnosis (30 days on OTV). Once the resistance mutation was identified, OTV was substituted by zanamivir and the infection resolved. In addition to mutations encoding resistance, variants associated with virulence were also sought. The D225G mutation was not found in any case, whereas the D225E variant was identified in three persistent cases but also in two non-persistent ones. In one patient, the D225E substitution coincided with the H275 resistant mutation., Conclusions: NAI-resistance mutations were detected, at rather different paces, in non-severe immunosuppressed cases with persistent infection by influenza A/H1N1v., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The study objective was to analyze the characteristics and the response to therapy in the eldest of the older adults living with human immunodeficiency virus., Methods: The study included a cohort of patients with human immunodeficiency virus aged 55 years or more on initiating highly active antiretroviral therapy (HAART). Immunologic and virologic response, morbidity, and mortality were assessed. Patients were categorized as aged less than 65 years and 65 years or more., Results: A total of 112 patients were included (82 patients aged<65 years and 30 patients aged> or =65 years). There were no differences between the age groups in baseline characteristics, survival, and virologic response. There was a trend toward better adherence and a lower CD4+ cell increase after HAART in the older group., Conclusion: A relationship was found between lower CD4+ cell increase after HAART and advanced age. We found the best adherence to treatment in the eldest of the older adults, and this has been shown to be the only protective independent factor related to virologic failure.

As with other nucleoside analogues, tenofovir (TDF) can be affected by several mutations in the reverse transcriptase gene. Most nucleoside analogue mutations (NAMs) are not induced specifically by TDF, although they can affect the activity of this drug. The impact of thymidine analogue mutations (TAMs) on tenofovir varies and, as with the remaining nucleoside analogue reverse transcriptase inhibitors, largely depends on the type and number present. Thus, the greater the number of TAMs, and the greater the number of type 1 TAMs, the more TDF activity will be affected. The 41L and 210W mutations have the greatest effect. The incidence of the 65R mutation was slight before the clinical introduction of TDF. This mutation was selected by treatments with zalcitabine monotherapy. However, after TDF came on to the market, the 65R mutation began to be more frequently reported and is currently the signature mutation of this drug. TDF has been shown to be safe and effective in patients with prior virological failure and resistance mutations in the reverse transcriptase gene. In these patients, the presence of the 41L and 210W mutations is associated with a worse response to rescue therapy containing TDF. In contrast, the presence of type 2 TAMs (67N, 70R and 219Q/E/N) has little effect on TDF activity in these patients. Importantly, in TDF therapy, the presence of the 184V mutation is associated with a more favorable virologic response than the absence of this mutation, with any of the distinct combinations of mutations present.

Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

Resistance to medication, adverse effects in the medium-long term, and cost are important limitations to lifelong adherence to highly active antiretroviral therapy (HAART). The combination of HAART with immune therapy to restore and/or boost immune-specific responses to HIV has been proposed, with the ultimate aim of controlling viral replication in the absence of HAART over long periods. The functional defects of the cellular and humoral responses would explain the lack of control of the immune system over viral replication. Different types of immune-mediated therapy have been investigated to solve these problems, including passive immune therapy, cytokines, structured treatment interruptions, immunosuppressors and therapeutic vaccines. Our still limited knowledge of immune mechanisms which can control HIV viral replication and of the causes of the deterioration of cellular and humoral immunity have produced only modest benefits in immune-mediated therapy, and are therefore confined to research for the time being. The availability of an optimal therapeutic vaccine would be an important scientific advance which could be compared with the arrival of protease inhibitors in clinical practice. Therefore, priority should be given to research in this field.

Objective: To provide an update of guidelines from the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS) committee on the prevention of opportunistic infections in adult and adolescent HIV-infected patients., Methods: These consensus recommendations have been produced by a group of experts from GESIDA and/or the PNS after reviewing the earlier document and the scientific advances in this field in the last years. The system used by the Infectious Diseases Society of America and the United States Public Health Service has been used to classify the strength and quality of the data., Results: This document provides a detailed review of the measures for the prevention of infections caused by viruses, bacteria, fungi and parasites in the context of HIV infection. Recommendations are given for preventing exposure and for primary and secondary prophylaxis for each group of pathogens. In addition, criteria are established for the withdrawal of prophylaxis in patients who respond well to highly active antiretroviral therapy (HAART)., Conclusions: HAART is the best strategy for the prevention of opportunistic infections in HIV-positive patients. Nevertheless, prophylaxis is still necessary in countries with limited economic resources, in highly immunodepressed patients until HAART achieves beneficial effects, in patients who refuse to take or who cannot take HAART, in those in whom HAART is not effective, and in the small group of infected patients with inadequate recovery of CD4+ T lymphocyte counts despite good inhibition of HIV replication.

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.

Objectives: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML)., Patients and Methods: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles., Results: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result., Conclusions: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.

The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.

We have evaluated the efficacy of fluconazole, 50 mg/day for 2 weeks, to treat oropharyngeal candidiasis in immunologically compromised patients. There were overall 27 patients, 25 of which were HIV+ and 2 had neutropenia. The rate of clinical response at the end of therapy, and one week and one month afterwards were 96%, 76% and 64%, respectively. The microbiological eradication was achieved in 36% of patients. The tolerance of the drug was satisfactory, although in 3 cases features of hepatic toxicity were detected. The convenience, good tolerance and clinical efficacy of fluconazole make it the therapy of choice for oropharyngeal candidiasis in immunologically compromised patients.