Introduction Adolescents and young adults living with HIV (AYHIV) face complex psychosocial and adherence challenges that compromise long-term treatment success. Long-acting injectable therapies (LA-ART), such as cabotegravir and rilpivirine, may improve adherence, reduce stigma, and facilitate treatment retention. Methods We conducted a retrospective, multicenter study of AYHIV enrolled in the Spanish pediatric HIV cohort (CoRISpe) and its adult extension (CoRISpe-FARO), who initiated LA-ART. Demographic, clinical, virological, immunological and biochemical data were analyzed up to March 2025. Outcomes before and after LA-ART initiation were analyzed, including CD4/CD8 ratio, viral suppression, and body mass index (BMI). Results Among 681 individuals in active follow-up, 26 AYHIV (65.4% women, median age 28) initiated LA-ART, primarily for treatment simplification. Most had acquired HIV perinatally and had extensive ART histories; 30% had received more than ten different ART regimens. Twenty-one patients had documented virological failures prior to LA-ART. Despite this, all patients achieved or maintained virological suppression after a median follow-up of 11 months. This included three individuals who initiated LA-ART with detectable viral load. CD4 and CD8 counts remained stable; the CD4/CD8 ratio showed an upward trend (p = 0.057), suggesting improved immune balance. Notably, AYHIV with BMI <30kg/m² showed significant increases in CD4 count, CD4%, and CD4/CD8 ratio. Overall BMI increased post-LA-ART (p=0.036), especially in women. Treatment was well tolerated, with only one discontinuation due to injection site pain. Conclusions LA-ART was safe, well tolerated, and effective in maintaining virological suppression, and showed positive immunological trends in AYHIV, including those with prior adherence issues or detectable viral load at baseline. These results support the potential of LA-ART as a valuable therapeutic strategy in AYHIV, especially in those with complex treatment histories and adherence challenges. Further prospective studies are warranted to confirm long-term outcomes.

This study aimed to analyse the long-term effect of direct-acting antivirals (DAAs) in vertically acquired HIV/HCV-coinfected youths. We performed a multicentre, longitudinal and observational study within the Spanish Cohort of HIV-infected children and adolescents and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO). We included HIV/HCV-coinfected youths (n = 24) that received DAAs between 2015 and 2017 with successful sustained viral response (SVR) with a subsequent follow-up of at least three years. Long-term evolution in liver disease severity and haematologic markers, lipid and immune profiles after SVR were assessed. Study times were the start date of DAAs treatment (baseline, T0) and 1, 2, 3, 4 and 5 years after SVR (T1, T2, T3, T4 and T5, respectively). We observed global improvements in liver function data that persist over time and a favourable haematologic and immune outcome at the long-term including a constant augment in leucocytes, neutrophils, neutrophils to lymphocytes ratio (NLR) and CD4/CD8 ratio over-time. Regarding the lipid profile, we found a significant increase in total cholesterol T2, total cholesterol/high-density lipoprotein (HDL) ratio at T4, triglycerides at T5, low-density lipoprotein (LDL) over time, and a decrease in HDL in all patients but with marked higher levels in the subgroup receiving anti-HIV Protease Inhibitor (PI)-based regimens. Comparisons of vertically HIV/HCV-coinfected youths after SVR at 3-year follow-up and a control group of vertically HIV-monoinfected youths never infected by HCV showed no significant differences in most variables analysed, suggesting a possible normalization in all parameters.

IntroductionThe high recombinogenic potential of HIV-1 has resulted in the generation of countless unique recombinant forms (URFs) and around 120 reported circulating recombinant forms (CRFs). Here we identify through analyses of near full-length genomes (NFLG) a new HIV-1 CRF derived from subtypes B and F1.MethodsHIV-1 protease-reverse transcriptase (Pr-RT) sequences were obtained by RT-PCR amplification from plasma RNA. Near full-length genome sequences were obtained after amplification by RT-PCR in 5 overlapping fragments. Phylogenetic sequence analyses were performed via maximum likelihood. Mosaic structures were analyzed by bootscanning and phylogenetic analyses of genome segments. Temporal and geographical estimations of clade emergence were performed with a Bayesian coalescent method.ResultsThrough phylogenetic analyses of HIV-1 Pr-RT sequences obtained by us from samples collected in Spain and downloaded from databases, we identified a BF1 recombinant cluster segregating from previously reported CRFs comprising 52 viruses, most from Brazil (n = 26), Spain (n = 11), and Italy (n = 9). The analyses of NFLG genomes of 4 viruses of the cluster, 2 from Spain and 2 from Italy, allowed to identify a new CRF, designated CRF75_BF1, which exhibits a complex mosaic structure with 20 breakpoints. All 4 patients harboring CRF75_BF1 viruses studied by us had CD4+ T-cell lymphocyte counts below 220/mm3 less than one year after diagnosis, a proportion significantly higher (p = 0.0074) than the 29% found in other patients studied in Spain by us during the same period. The origin of the clade comprising CRF75_BF1 and related viruses was estimated around 1984 in Brazil, with subsequent introduction of CRF75_BF1 in Italy around 1992, and migration from Italy to Spain around 1999.ConclusionA new HIV-1 CRF, designated CRF75_BF1, has been identified. CRF75_BF1 is the 6th CRF of South American origin initially identified in Western Europe, reflecting the increasing relationship of South American and European HIV-1 epidemics. The finding of low CD4+ T-cell lymphocyte counts early after diagnosis in patients harboring CRF75_BF1 viruses warrants further investigation on the virulence of this variant.

BACKGROUND:This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS:PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS:Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS:Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION:EudraCT: 2020-001156-18.

BACKGROUND:Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV.METHODS:Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods.RESULTS:Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition.CONCLUSIONS:After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

BACKGROUND:Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients.METHODS:Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed.RESULTS:HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12].CONCLUSION:HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a technique that enables study of human cells obtained through aspiration in different locations near the gastrointestinal tract. Access routes described in the literature to obtain samples of cervical and thoracic regions are open biopsy and computed tomography (CT)-guided biopsy. These techniques have some disadvantages as invasiveness and risk of complications in the case of open biopsy, as well as radiation emitted to the patient and not being a real time technique in the case of CT-guided biopsy. We describe use of EUS-FNA as a novel approach able to target the cervical and thoracic regions in real time. We present our experience in the field of spondylodiscitis (cervical and thoracic), with the main objective of establishing debate on the possibilities of endoscopic ultrasound in this very complex anatomical area.

OBJECTIVE:To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients.METHODS:The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used.RESULTS:A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038).CONCLUSION:The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Our aims were to investigate the adherence to national guidelines of initial antiretroviral therapy (ART) in the Spanish multicenter CoRIS cohort during the years 2010–2015, to identify the reasons for the prescription of nonrecommended treatments, and to explore the role of institutional constraints to guideline compliance. ART regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Physicians were asked the reasons for prescribing nonrecommended regimens. Factors associated with the prescription of non recommended regimens were assessed using multivariable logistic regression. During the study period, 586 (10.7%) of 5479 patients who started ART were given a regimen not recommended in the guidelines. The most frequent reasons for prescribing nonrecommended regimens were: enrolment in clinical trials (43.3%), comorbidities and/or interactions (10.2%), pregnancy (8.7%), and cost (7.7%). Among 37 participating centers, 16 (43%), treating 3561 patients, reported limitations related with the cost of ART, and 20 (54%), treating 1365 patients, reported restrictions for prescribing at least one recommended antiretroviral. In multivariable analysis, a higher risk of receiving nonrecommended regimens was associated with male gender, HIV acquisition by heterosexual transmission, low viral loads, initiation of treatment during the years 2011 to 2015, and initiation of treatment in a center with restricted access to at least one antiretroviral drug. Compliance to clinical guidelines was high. A high proportion of centres reported cost limitations for ART or restricted access to at least one recommended antiretroviral drug, with a significant impact on the choice of initial regimens. Nuestros objetivos fueron investigar la adecuación del tratamiento antirretroviral (TAR) inicial a las guías nacionales en la cohorte multicéntrica española CoRIS durante los años 2010-2015, identificar las razones para la prescripción de pautas no recomendadas y estudiar la influencia de limitaciones institucionales en el cumplimiento de las guías. Se clasificaron las pautas de TAR en recomendadas, alternativas o no recomendadas según las guías de GeSIDA/Plan Nacional sobre el sida. Se preguntaron las razones para haber prescrito pautas no recomendadas a los médicos prescriptores. Se evaluaron los factores asociados a la prescripción de pautas no recomendadas mediante regresión logística multivariable. Durante el periodo de estudio 586 (10,7%) de 5.479 pacientes que iniciaron TAR recibieron una pauta no recomendada. Las razones más frecuentes para prescribir pautas no recomendadas fueron: participación en ensayo clínico (43,3%), comorbilidades y/o interacciones (10,2%), embarazo (8,7%) y coste (7,7%). Entre los 37 centros participantes 16 (43%), que incluían 3.561 pacientes, referían limitaciones en el coste del TAR y 20 (54%), que incluían 1.365 pacientes, referían restricciones para la prescripción de al menos un fármaco recomendado. En el análisis multivariable el riesgo de recibir una pauta no recomendada se asoció a ser varón, adquisición del VIH por vía heterosexual, carga viral baja, inicio del tratamiento durante los años 2011 a 2015 e inicio del tratamiento en un centro con acceso restringido al menos a un antirretroviral. El cumplimiento de las guías de TAR fue elevado. Una alta proporción de centros refirieron limitaciones de coste para el TAR o acceso restringido al menos a uno de los fármacos antirretrovirales recomendados; esto último influyó en la elección de pautas no recomendadas.

INTRODUCTION:We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality.METHODS:All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected.RESULTS:Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality.CONCLUSIONS:Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

OBJECTIVE:To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients.METHODS:The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy.RESULTS:Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0).CONCLUSION:The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

Objective: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). Methods: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. Results: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child–Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1–Q3) duration of sorafenib treatment was 70 (31–158) days. Median survival was 7.2 months, whereas the median (Q1–Q3) duration of overall survival after the start of treatment was 4 (2–9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4+ cell counts and HIV viral load remained stable. Conclusion: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

To analyse the influence of educational levels on diverse baseline and follow-up characteristics and outcomes of HIV-infected patients, we sequentially evaluated 1352 individuals with known educational levels, who initiated a nelfinavir-based regimen. Higher educational degrees were associated with better baseline clinical (P=0.03) and immunological (P=0.003) conditions, not related to transmission categories, which were also observed during follow-up (P=0.003). However, these differences were only found in antiretroviral-experienced patients (P=0.002), while naive patients had very similar values (P=0.8). Overall, there were different CD4 responses (P=0.06), but not viral load responses (P=0.6), to antiretroviral therapy according to the educational level, but these differences were more marked in the last six months of follow-up (P=0.008). Patients with higher educational degrees had higher rates of adherence to medical appointments both before (P=0.0003) and during the study period (P=0.01), as well as to antiretroviral therapy in univariate (P=0.003) and multivariate analyses (P=0.007). Similarly, baseline CD4 counts proved to be independently associated with education after adjustment for other variables (P=0.0006). The educational groups also differed in diverse socioeconomic parameters and certain beliefs about HIV infection (P<0.0001 for each). We conclude that the patient's educational level influences clinical and immunological outcomes of HIV infection. This impact is probably mediated through differences in the long-term effects of treatment, as a result of adherence to antiretroviral therapy and to medical indications. The evaluation of social aspects such as the patient's education should be incorporated into routine clinical practice to improve the results of treatment.

Sexual disturbances develop in some patients treated with highly active antiretroviral therapy (HAART). To evaluate sexual dysfunction and the influence that different antiretrovirals could have on those parameters, we conducted a prospective study in patients with stable clinical condition attending an HIV outpatient clinic. A total of 351 evaluations were performed in 189 HIV-infected men, who were interviewed about symptoms of sexual dysfunction. Sexual hormones as well as other clinical and laboratory parameters were also measured at the time of each evaluation. The mean CD4 count was 451.1 x 10(6) cells/L, and viral load was undetectable in two thirds of the determinations. The prevalence of sexual dysfunction was 19.5% overall, but it was influenced by treatment, particularly (although not exclusively) by protease inhibitors (PIs) (27.1% vs. 3.8% for untreated patients). Sexual dysfunction was not related to hypophyseal or gonadal hormonal values. Although several parameters were associated with sexual dysfunction in the univariate analysis, only antiretroviral treatment was significantly predictive of this disorder in a logistic regression analysis. Sexual dysfunction is common in HIV-infected patients in stable clinical condition receiving HAART, and all antiretroviral drugs, particularly PIs, seem to be related to it. Sexual dysfunction in these patients is not related to hormonal causes.

We found that patients receiving antiretroviral therapy had higher cortisol levels than those untreated, with the highest levels corresponding to those taking efavirenz. Multivariate analysis revealed that only the presence of antiretroviral therapy, treatment with efavirenz and a prior diagnosis of AIDS were significantly predictive of cortisol levels.

In a total of 372 determinations of thyroid hormones in HIV-infected patients we found a correlation between free thyroxine and CD4 cell counts, which was maintained after stratification by CD4 cell count and therapeutic groups, and was confirmed by multivariate analysis. Patients with normal free thyroxine had higher CD4 cell counts than those with low free thyroxine. Anti-retroviral drugs did not influence free thyroxine levels. Our results support an interrelationship between the thyroid axis and the immune system.

The prevalence of hyperlipidemia and factors related to it have been studied in a large sample of patients. We found a significant association between hyperlipidemia and the duration of antiretroviral therapy, serum cortisol levels, the presence of lipodystrophy, certain antiretroviral regimens and, especially, the absence of hepatitis C virus (HCV) infection. Patients co-infected with HCV had considerably lower rates of hyperlipidemia than non-infected patients, and this effect was particularly evident in patients treated with antiretroviral drugs. The presence of hyperlipidemia in patients taking protease inhibitors (PI) compared with PI-naive patients or HIV-negative controls has been reported as a part of the lipodystrophy syndrome [1–4], as well as improvements in lipid abnormalities after switching from PI-based to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens [5]. The present study was carried out to evaluate the prevalence of hyperlipidemia in a large group of HIV-infected patients attending an outpatient clinic, and the factors associated with this disturbance. The data were extracted from a database of HIV-infected men, most of whom were past intravenous drug users. The study group was composed of 197 patients, who underwent a total of 368 clinical and laboratory evaluations. The number of determinations per patient ranged from one to four, each separated by a mean interval of 27.4 weeks. All patients were clinically stable and did not have any acute severe illness at the time of sampling. All samples were obtained at between 8.00 and 8.30 a.m. after an overnight fast. Hyperlipidemia was defined as total cholesterol or triglyceride levels greater than 200 mg/dl. Differences between groups were assessed using the Mann–Whitney U test and the chi-square test as appropriate. A stepwise logistic regression analysis was used to identify the independent association of the studied variables with the presence of hyperlipidemia. A P value of less than 0.05 for a two-sided test was considered statistically significant. The mean age of the patients was 36.8 years, the mean CD4 cell count was 452.1 × 106/l, and 64% had an undetectable viral load. Hyperlipidemia was observed in 59 of the 197 patients (29.9%) and in 112 of the 368 determinations (30.4%). Hyperlipidemic patients were receiving antiretroviral therapy for longer periods (mean 26.7 versus 24.4 months, P = 0.049), and had higher serum cortisol levels (mean 618 versus 552 nmol/l, P = 0.002) than patients without hyperlipidemia. We did not find significant differences with respect to age, testosterone, 17β-estradiol, thyroid hormones, CD4 cell count, viral load, or a previous diagnosis of AIDS. Regarding other metabolic complications, we found that 38.8% of the lipodystrophic patients had hyperlipidemia compared with 27.7% of the non-lipodystrophic patients (P = 0.049). There were no differences regarding the existence of diabetes mellitus (P = 0.8). When patients with other metabolic disturbances such as lipodystrophy and diabetes were excluded, we also found an association of hyperlipidemia with longer periods of antiretroviral therapy (mean 26.7 versus 23.3 months, P = 0.007), and higher cortisol values (mean 618 versus 555 nmol/l, P = 0.004). Table 1 shows the comparison of patients with hyperlipidemia with those without hyperlipidemia or without other metabolic complications according to the antiretroviral therapy and hepatitis C virus (HCV) status. Patients treated with efavirenz had higher rates of hyperlipidemia than patients treated with nevirapine (49 versus 20.7%, respectively, P = 0.002) and than patients treated with PI (31.5%, P = 0.02), differences that were also observed when other metabolic disturbances were excluded (64.1 versus 24.5%, P = 0.0002, and versus 39.2%, P = 0.007, respectively).Table 1: Hyperlipidemia according to antiretroviral treatment and hepatitis C virus infection.Sequential evaluations of hyperlipidemia over time did not reveal significant differences (29.9, 31.5, 33.3, and 25%, respectively, P = 0.9). A logistic regression analysis of all variables studied selected absence of infection with HCV [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.13–0.44, P < 0.001], serum cortisol (OR 1.05, 95% CI 1.01–1.09, P = 0.01), lipodystrophy (OR 1.96, 95% CI 1.06–3.61, P = 0.03) and duration of highly active antiretroviral therapy (HAART; OR 1.03, 95% CI 1.01–1.05, P = 0.02) as the only variables independently associated with hyperlipidemia. Only when the latter was excluded, were NNRTI (OR 2.29, 95% CI 1.31–3.98, P = 0.004) and PI treatment (OR 2.04, 95% CI 1.16–3.57, P = 0.01), in addition to the other three variables, selected as predictors of hyperlipidemia. Some studies have also found that hyperlipidemia is associated with lipodystrophic changes [1,2,6,7], although others failed to find differences in PI-treated patients [8]. We also found that the period of treatment was a predictor of hyperlipidemia. In fact, antiretroviral drugs were associated with hyperlipidemia only when this factor was removed from the logistic regression analysis. Duration of therapy is considered a risk factor for lipodystrophy [1,2,8]. Although we are unaware of any study reporting a similar relationship with hyperlipidemia, our results are not unexpected. We also found higher rates of hyperlipidemia in patients treated with efavirenz than those treated with nevirapine or PI, an aspect important when planning a change in the antiretroviral regimen and an association of hyperlipidemia with higher cortisol levels. Although hypercortisolemia, a known cause of insulin resistance, might contribute to the lipid disorders in these patients, its role is probably minor. More interesting is our finding that patients co-infected with HCV had an appreciably lower rate of hyperlipidemia than HCV-negative individuals. These differences cannot be ascribed to different adherence to therapy because the rate of undetectable viral load in treated patients was very similar (66.4 versus 67.9%, respectively, P = 0.8). Lower cholesterol and triglyceride levels were also observed in a small group of HIV/HCV-co-infected patients despite increased insulin resistance [9]. Considering that up to 80% of HCV infections progress to chronic hepatitis, this feature probably relates to HCV-induced hepatic dysfunction. In a study [10], cholesterol levels were lower in patients with chronic active hepatitis than in healthy controls, and in cirrhotic patients than in patients with chronic active hepatitis and control individuals. However, differences in the lipid composition depending on the viral agent of chronic hepatitis have been reported [11], cholesterol values being significantly lower in patients with chronic HCV infection than in patients with chronic hepatitis B virus infection. Similarly, we found remarkable differences between these two aetiologies, also suggesting a specific role of the viral agent. Finally, it is noteworthy that the beneficial effect of HCV infection on hyperlipidemia was non-existent in the absence of HAART, but was very marked when HAART was present. Consequently, the interactions of HAART on lipidic metabolism seem to be neutralized by the HCV infection. Interestingly, we found the opposite regarding lipodystrophy in HAART-treated patients, because HCV-infected individuals had higher rates of lipodystrophy than HCV-negative patients (27.0 versus 11.8%, respectively, P = 0.007), a finding supported by others in a small group of patients [9]. Therefore, our results suggest that antiretroviral therapy does not seem to affect the lipidic profile of HCV-co-infected patients negatively, which may contribute to alleviate the safety concerns in this population.