Misconceptions about HIV infection in Kinshasa (Democratic Republic of Congo): a case-control study on knowledge, attitudes and practices.

OBJECTIVES: To evaluate the prevalence of HIV-related misconceptions in an outpatient centre of Kinshasa (Democratic Republic of Congo) and analyse the association between these beliefs and HIV infection. METHODS: A case-control study was carried out from December 2010 until June 2012. We assessed 1630 participants aged 15-49 attending a primary outpatient centre in Kinshasa: 762 HIV Voluntary Counselling and Testing attendees and 868 blood donors. A 59-item questionnaire about knowledge, attitudes and practice was administered during a face-to-face interview, followed by an HIV test. Cases and controls were respondents with a newly diagnosed HIV-positive or HIV-negative test, respectively. Unconditional logistic regression was used to analyse the association between misconceptions and HIV seropositivity. RESULTS: 274 cases and 1340 controls were recruited. Cases were more likely than controls to have a low socioeconomic status, no education, to be divorced/separated or widowed. An association was found between the following variables and HIV seropositivity: having a poor HIV knowledge (adjusted OR=2.79; 95% CI 1.43 to 5.45), not knowing a virus is the cause of AIDS (adjusted OR=2.03; 95% CI 1.38 to 2.98) and reporting more than three HIV-transmission-related misconceptions (adjusted OR=3.30; 95% CI 1.64 to 6.64), such as thinking an HIV-positive person cannot look healthy and that HIV is transmitted by sorcery, God's punishment, a kiss on the mouth, mosquitoes, coughs/sneezes or undercooked food. CONCLUSIONS: Despite having access to healthcare services, there are still many people in Kinshasa that have HIV-related misconceptions that increase their HIV risk. Our findings underscore the need for a culturally adapted and gender-orientated basic HIV information into Congolese HIV prevention programmes.

Emerging challenges in managing hepatitis B in HIV patients.

Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV.

Hepatitis delta is a major determinant of liver decompensation events and death in HIV-infected patients.

BACKGROUND: Coinfection with hepatitis viruses is common in individuals infected with human immunodeficiency virus (HIV) and has become a leading cause of complications and death in those receiving antiretroviral therapy (ART). METHODS: We retrospectively examined the effect of coinfection with hepatitis B, C, and/or D viruses (HBV, HCV, HDV, respectively) on liver decompensation events (ascites, variceal bleeding, encephalopathy, and/or hepatocellular carcinoma) and liver-related mortality in HIV-positive patients on regular follow-up since the year 2004 at a reference HIV clinic in Madrid, Spain. RESULTS: A total of 1147 HIV-infected patients (mean age, 42 years; 81% males; 46% intravenous drug users, 85.4% on ART) were analyzed. Mean follow-up was 81.2 ± 17.8 months. At baseline, 521 patients (45.4%) were HCV-antibody positive, 85 (7.4%) were hepatitis B surface antigen positive, and 17 (1.5%) were anti-HDV positive. A total of 233 HIV/HCV-coinfected patients received antiviral therapy for HCV, of whom 106 (45%) achieved sustained virologic response (SVR). Overall, 15 patients died of liver-related complications and 26 developed hepatic decompensation events. Taking as controls the 524 HIV-monoinfected patients, HDV coinfection (adjusted hazard ratio [AHR], 7.5; 95% confidence interval [CI], 1.84-30.8; P = .005) and baseline liver stiffness (AHR, 1.1; 95% CI, 1.07-1.13; P < .0001) were associated with a higher rate of liver-related morbidity and mortality. In contrast, SVR following hepatitis C therapy in HIV/HCV-coinfected patients was protective (AHR, 0.11; 95% CI, .01-.86; P = .03). CONCLUSIONS: Hepatitis delta is associated with a high rate of death and liver decompensation events in HIV-infected patients on ART.

Scaling up epidemics of acute hepatitis C and syphilis in HIV-infected men who have sex with men in Spain.

BACKGROUND: Outbreaks of acute hepatitis C in HIV-positive men who have sex with men (MSM) are being reported in large cities in western countries along with increasing rates of sexually transmitted diseases. METHODS: All HIV individuals attended at a large outclinic in Madrid within the last 5 years were examined. Incident syphilis was diagnosed based on rapid plasma reagin (RPR) reactivity, being negative previously or showing >4-fold increase. Acute hepatitis C was diagnosed based on HCV antibody seroconversion and/or positive serum HCV-RNA after being negative within the last year. RESULTS: A total of 859 episodes of syphilis and 19 of acute hepatitis C were diagnosed during the study period. Syphilis was recognized in 65/2,094 (3.1%) individuals attended in 2008 and rose up to 261/2,512 (10.4%) in 2012 (P < 0.001). Acute hepatitis C was diagnosed in only one subject in 2008 but rose up to 7 in 2012 (P = 0.12). All 19 HIV patients with acute hepatitis C were MSM. Syphilis was diagnosed concomitantly in seven. All eight individuals who were treated with peginterferon/ribavirin were cured, whereas only one untreated experienced spontaneous clearance (P = 0.004). Two clusters of infections by HCV genotypes 4 and 1a were identified by phylogenetic analyses. CONCLUSIONS: The incidence of acute hepatitis C is low but steadily increasing in HIV-positive MSM in Madrid (<1% yearly), despite the very high rates of syphilis (currently 20% yearly in HIV-positive MSM). Preventive measures for sexually transmitted infections and periodic HCV screening are warranted in this population as treatment of acute hepatitis C is very effective.

Update on HIV/HCV coinfection.

Liver disease is currently one of the leading causes of hospitalization and death in HIV-positive individuals. Coinfection with the hepatitis C virus (HCV) is a major contributor to this trend. Besides hepatic damage, which is enhanced in the presence of HIV-associated immunosuppression, HCV may contribute to disease in coinfected individuals by potentiating immune activation and chronic inflammation, which ultimately account for an increased risk of cardiovascular events, kidney disease, and cancers in this population. Fortunately, hepatitis C therapeutics has entered a revolutionary era in which we hope that most patients treated with the new oral direct-acting antivirals (DAA) will be cured. However, many challenges preclude envisioning a prompt elimination of HCV from the coinfected population. Issues that should be addressed include the following: (1) rising incidence of acute hepatitis C in men who have sex with men, and expansion/recrudescence of injection drug use in some settings/regions; (2) adverse drug interactions between antiretrovirals and DAA; and (3) high cost of DAA, which may lead many to defer or fail to access appropriate therapy.

Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-α for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial.

BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.

Management and treatment of chronic hepatitis C in HIV patients.

Progression to cirrhosis occurs faster whereas response to peginterferon/ribavirin therapy is lower in patients with chronic hepatitis C coinfected with human immunodeficiency virus (HIV), as compared with hepatitis C virus (HCV) monoinfected individuals. The use of antiretroviral therapy may ameliorate poor outcomes in HIV/HCV coinfected patients. However, in the best scenario peginterferon/ribavirin therapy provides cure to 30% of patients harboring HCV genotypes 1 or 4 and to 70% of HCV genotypes 2 or 3 carriers, a rate lower than that seen in HCV monoinfection. Moreover, a substantial proportion of HIV/HCV coinfected patients are not treated due to contraindications, or do not complete therapy due to serious adverse events, or just do not wish to receive such a poorly tolerated medication. For these reasons, the advent of direct acting antivirals (DAA) has been eagerly awaited for treating HIV/HCV coinfected patients. However, new challenges have arisen, including the potential for harmful drug interactions with antiretroviral agents, poor drug adherence due to polymedication, increased risk for selection of drug-resistant HCV mutants, and unaffordable coverage in an environment of economic constraints. The use of noninvasive tools to measure liver fibrosis (i.e., elastometry) and pharmacogenomics (testing for IL28B and perhaps ITPA polymorphisms), along with consideration of early viral kinetics to guide length and drugs needed could help to individualize and improve the cost effectiveness of therapeutic decisions using DAA in HIV-infected patients with chronic hepatitis C.

Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral treatment-naïve HIV-infected patients (CoRIS) are due to recombinant viruses.

HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected.

Pharmacogenetics of hepatitis C.

Recent discoveries have highlighted the influence of host genomics on hepatitis C virus (HCV) infection outcomes. As a result, our views on hepatitis C pathogenesis and therapeutic approaches have been transformed. The recognition of the impact of single-nucleotide polymorphisms (SNPs) of the genes interleukin 28B (IL28B), inosine triphosphatase (ITPA) and low-density lipoprotein cholesterol receptor (LDLR) may lead to refinements in the pharmacogenomic prediction of antiviral response and drug-related toxicities and favour the discovery of new therapeutic targets for hepatitis C. Although the relevance of host genetics may be less in the setting of very potent new direct-acting antivirals (DAAs), genetic markers may continue to aid decision making regarding the length of therapy. Moreover, in several populations, such as HIV/HCV-coinfected patients, current therapy with peginterferon-α/ribavirin will continue in use for most patients, and thus host factors will retain their predictive value for treatment outcomes for a while.

Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction.

BACKGROUND: Tenofovir (TFV) causes kidney tubular dysfunction (KTD) in some patients, but the mechanism is poorly understood. Genetic variants in TFV transporters are implicated; we explored whether ABCC10 transports TFV and whether ABCC10 single-nucleotide polymorphisms (SNPs) are associated with KTD. METHODS: TFV accumulation was assessed in parental and ABCC10-transfected HEK293 cells (HEK293-ABCC10), CD4(+) cells and monocyte-derived macrophages (MDMs). Substrate specificity was confirmed by cepharanthine (ABCC10 inhibitor) and small interfering RNA (siRNA) studies. Fourteen SNPs in ABCC10 were genotyped in human immunodeficiency virus-positive patients with KTD (n = 19) or without KTD (controls; n = 96). SNP and haplotype analysis was performed using Haploview. RESULTS: TFV accumulation was significantly lower in HEK293-ABCC10 cell lines than in parental HEK293 cells (35% lower; P = .02); this was reversed by cepharanthine. siRNA knockdown of ABCC10 resulted in increased accumulation of TFV in CD4(+) cells (18%; P = .04) and MDMs (25%; P = .04). Two ABCC10 SNPs (rs9349256: odds ratio [OR], 2.3; P = .02; rs2125739, OR, 2.0; P = .05) and their haplotype (OR, 2.1; P = .05) were significantly associated with KTD. rs9349256 was associated with urine phosphorus wasting (P = .02) and ß2 microglobulinuria (P = .04). CONCLUSIONS: TFV is a substrate for ABCC10, and genetic variability within the ABCC10 gene may influence TFV renal tubular transport and contribute to the development of KTD. These results need to be replicated in other cohorts.

Impact of inosine triphosphatase gene variants on the risk of anemia in HIV/hepatitis C virus-coinfected patients treated for chronic hepatitis C.

The role of rs1127354/rs7270101 alleles at the inosine triphosphatase (ITPA) gene on ribavirin-induced anemia was assessed in 74 patients with hepatitis C virus and human immunodeficiency virus coinfection. Anemia developed in 80% of patients with normal ITPA activity compared with 33% of those with reduced ITPA activity. In contrast, ITPA variants did not influence sustained virological response.

Directly acting antivirals against hepatitis C virus.

The approval of directly acting antivirals (DAA) for the treatment of chronic hepatitis C virus (HCV) infection will represent a major breakthrough for the 180 million persons infected worldwide. Paradoxically, hepatitis C is the only human chronic viral disease that can be cured, as all other pathogenic viruses infecting humans either display self-limited courses or establish non-eradicable persistent infections. Until now, treatment of chronic hepatitis C consisted of the combination of peginterferon-α plus ribavirin, which provided limited rates of cure and was associated with frequent side effects. Several DAA have been identified that inhibit the NS3 protease, the NS5B polymerase or the NS5A replication complex, and have entered the final steps of clinical development. These molecules, coupled with significant progress made in the recognition of more potent and safe interferon forms (e.g. interferon-λ) and host protein targets (e.g. alisporivir), are opening a new era in hepatitis C therapeutics. The expectations are so great that, to some extent, it is reminiscent of what happened in 1996 in the HIV field when the introduction of the first protease inhibitors as part of triple combinations revolutionized antiretroviral therapy. To maximize treatment success and reduce the likelihood of drug resistance selection, a proper individualization of hepatitis C therapy will be required, choosing the most convenient drugs and strategies according to distinct viral and host profiles. The complexity of HCV therapeutics has reached a point that presumably will lead to the birth of a new specialist, the HCV doctor.

Impact of antiretroviral therapy on the variability of the HCV NS5B polymerase in HIV/HCV co-infected patients.

OBJECTIVES: Assessment of the impact of antiretroviral drugs on the variability of hepatitis C virus (HCV) NS5B polymerase in HIV/HCV co-infected individuals. METHODS: HCV NS5B polymerase was sequenced from plasma at baseline and at the end of follow-up in HIV/HCV co-infected individuals on a stable antiretroviral regimen seen at two outpatient clinics for at least 2 years. The presence of mutations associated with drug resistance to experimental HCV polymerase inhibitors was examined. RESULTS: Sixty-one HIV/HCV co-infected patients (34% HCV-1a, 25% HCV-1b, 18% HCV-3 and 23% HCV-4) were analysed. The mean time on antiretroviral therapy was 52 months. All patients received HIV nucleoside analogues; 66% along with non-nucleoside analogues. The median HCV RNA was 6.1 log at baseline and 6 log IU/mL at the end of follow-up. The median HIV RNA was 4.4 log at baseline and 1.5 log copies/mL at the end of follow-up. No evidence of selection of NS5B polymerase inhibitor resistance mutations was seen when comparing samples collected at baseline and at the end of follow-up from the same individuals. All NS5B sequences from HCV-1a and HCV-3 showed V499A, associated with resistance to HCV non-nucleoside site-1 inhibitors (NNI-1). In addition, HCV-3 showed I482L, associated with resistance to NNI-2, and HCV-4 showed M414L, I482L and V499A, associated with resistance to NNI-3, 2 and 1, respectively. Two HCV-1b patients showed C316N, related with resistance to NNI-4. CONCLUSIONS: The use of antiretroviral drugs does not increase the rate of primary drug resistance mutations to HCV NS5B polymerase inhibitors in HIV/HCV co-infected patients. However, natural polymorphisms associated with reduced susceptibility to some HCV NNIs are common, particularly in HCV variants other than HCV-1b.

[Human immunodeficiency virus infection and viral hepatitis]. / Infección por virus de la inmunodeficiencia humana y hepatitis víricas.

Hepatic complications currently represent one of the leading reasons for medical consultations, hospitalisation, and death in the HIV-infected population. This is due to a large extent to viral hepatitis, given its disproportionate frequency in this population. Chronic hepatitis B affects 5-10% of the HIV-infected population. Vaccination has reduced the incidence of liver disease related to hepatitis-B virus (HBV), and the availability of tenofovir has dramatically improved the prognosis of HIV/HBV carriers. Delta hepatitis affects around 15% of HIV-infected individuals in Europe harbouring positive HBsAg. It has the worst prognosis, given its accelerated course to cirrhosis and the absence of successful therapy. Lastly, chronic hepatitis C is the major cause of liver disease in the HIV population. Although classically linked to persons infected parenterally (i.e., intravenous drug users), outbreaks of acute hepatitis C among homosexual men have been reported over the last decade. Treatment with pegylated interferon plus ribavirin provides a cure in less than 40% of patients. However, the introduction of new direct acting antivirals against hepatitis- C virus (HCV) (telaprevir, boceprevir) has revolutionised the field, as HAART did in 1996 in the HIV field, improving the prognosis of co-infected patients. However, interactions between these drugs and antiretroviral agents and the risk of selective resistance pose huge threats in this population.

[The Cohort of the Spanish HIV Research Network (CoRIS) and its associated biobank; organizational issues, main findings and losses to follow-up]. / La cohorte de la red española de investigación en sida y su biobanco: organización, principales resultados y pérdidas al seguimiento.

INTRODUCTION: This article describes the development of the Cohort of the Spanish Research Network (CoRIS), its methodological and organizational aspects, the demographic and clinical characteristics of the subjects enrolled and quantifies the losses to follow-up and associated factors. METHODS: Multicentre cohort of HIV-positive naïve subjects recruited in 28 sites of Spain from 2004-onwards. Missing and inconsistent data were submitted to internal quality controls and the datasets were externally audited. Multiple logistic regression models were used. RESULTS: As of October 2009, 5,514 subjects had been recruited, representing 11,708 person-years with a median follow-up time of 1.81 years. Most are men (78.8%), infected by sexual transmission (46.1% men who have sex with men and 35.2% heterosexual persons) and Spanish (69.7%). During follow-up 64.5% have started Antiretroviral Therapy (ART) and 201 deaths have occurred. New HIV diagnoses accounted for 80.7% of the sample. Some 52% of subjects had at least one baseline sample in the BioBank while naïve to ART. Losses to follow-up (18.9%) were more frequent in younger people, in injecting drug users, in persons of non-Spanish origin, in persons with primary or lower educational level, and in those with a CD4 count over 350 cells/mm(3) at time of recruitment. CONCLUSIONS: The implementation of CoRIS has been successful; the cohort has wide representation at national level, is actively recruiting new members and blood samples, and has excellent data quality. Losses to follow-up are of similar magnitude to other cohort studies, as are the factors associated with them.

Influence of a single nucleotide polymorphism at the main ribavirin transporter gene on the rapid virological response to pegylated interferon-ribavirin therapy in patients with chronic hepatitis C virus infection.

The equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in ribavirin cellular uptake. Polymorphisms at the ENT1 gene may influence ribavirin activity as part of hepatitis C virus (HCV) therapy. A retrospective study was conducted in 109 human immunodeficiency virus (HIV)-infected patients who were infected with HCV genotypes 1 or 4 who had received pegylated interferon (pegIFN)-ribavirin. Single nucleotide polymorphisms (SNPs) at the ENT1 gene were examined using TaqMan 5'-nuclease assays. In the study population, allelic frequencies at rs760370 were as follows: A3 (43 [39%] of 109 patients), AG (50 [46%] of 109 patients), and GG (16 [15%] of 109 patients). Achievement of rapid virological response was more frequent in GG carriers than in AA/AG carriers (50% vs 17%, respectively; P = .007). In multivariate analysis, the GG genotype (odds ratio [OR], 15.9; 95% confidence interval [CI], 2.8-92.2; P < .002), a baseline serum HCV-RNA level <600,000 IU/mL (OR, 45.7; 95% CI, 8.7-240.5; P <.001) and a serum ribavirin trough concentration >2.5 µg/mL (OR, 4.8; 95% CI, 1.3-17.1; P < .016) were associated with rapid virological response. When 2 or more of these factors were present, positive and negative predictive values of rapid virological response were 65% and 91%, respectively. In summary, a SNP rs760370A→G at the ENT1 gene influences the chance of rapid virological response to pegIFN-ribavirin therapy in HIV-infected patients with chronic HCV infection due to HCV genotypes 1 or 4, most likely modulating intracellular ribavirin exposure within hepatocytes.

Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection experience antiretroviral-associated liver toxicity more frequently than HIV mono-infected persons. Herein, we report the hepatic safety profile of raltegravir in a relatively large group of HIV/HCV co-infected patients, a population that was poorly represented in the registrational studies. METHODS: Prospective, observational study of all antiretroviral-experienced HIV-infected patients who initiated raltegravir from January 2006 to January 2009 at a reference HIV clinic. Clinical data, laboratory parameters and liver stiffness measured at baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined following the AIDS Clinical Trials Group definition for liver enzyme elevations (LEEs). A control group of patients who initiated protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly. RESULTS: Data from 218 HIV-infected patients on raltegravir were analysed, 126 HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co-infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three subjects other reasons than raltegravir exposure most likely explained LEEs. Multivariate analysis revealed HCV co-infection as the only independent variable associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally, the rate of LEEs in patients on raltegravir was lower than in those who were treated with PIs or NNRTIs. CONCLUSIONS: LEEs are less frequent in patients treated with raltegravir than with other antiretroviral drug classes. However, HIV/HCV co-infected patients treated with raltegravir experienced LEEs more frequently than HIV mono-infected persons. In this series, LEEs in patients treated with raltegravir were uniformly mild and no cases of grade 3-4 hepatotoxicity could be directly attributed to the drug. These results reinforce the overall hepatic safety profile of raltegravir.

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain.

BACKGROUND: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

[Factors related to non-prescription of tuberculin skin testing in a cohort of HIV-infected people]. / Factores asociados con la no realización de la prueba de la tuberculina en una cohorte de pacientes VIH positivos.

INTRODUCTION: Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. PATIENTS AND METHODS: Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. RESULTS: A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1-6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3-1.0), having a CD4 cell count >200 (CD4 200-499: OR 0.5, 95% CI 0.3-0.9. CD4> or =500: OR 0.3, 95% CI 0.2-0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1-0.5) were associated with a lower probability. CONCLUSIONS: In this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians' expectations regarding the results of the test and the patients' adherence to treatment for latent TB infection.