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7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Background A significant number of HIV Mexican infected people are in virological failure, many of them are multiply experienced to antiretroviral therapy. Objective To assess the prevalence of resistance mutations [...]

Introduction and Aim: Timely detection and diagnosis of hepatitis C virus (HCV) involves identifying the population that is predisposed to treatment and prevention, thus limiting complications and preventing infection. The aim of this study was to analyze and describe risk factors associated with anti-HCV antibody detection in a population with access to public healthcare that participated in a national screening program., Material and Methods: An analytic cross-sectional study was conducted that utilized data related to rapid tests carried out between September 2021 and October 2022 in 26 of the 32 states of Mexico. Anti-HCV reactive tests were selected, according to age and sex, for analyzing and comparing possible risk factors through descriptive and inferential statistics. The geographic distribution and density of the screening program at the state and municipal levels was analyzed., Results: There were 75,185 anti-HCV antibody detections, 2,052 reactive tests, and mean participant age was 44.3 years (±15.1). Occupation: 32.3% were employees, 19% were housewives, and 18.2% were healthcare workers. Five out of every 10 cases had no indication of risk factors, but there was a 1.4 and 5-times greater likelihood of anti-HCV detection in men with a history of sharps injury or intravenous psychoactive substance use, compared with women. Regarding place of residence, 80% of the reactive tests were concentrated in the State of Mexico, Mexico City, and Guanajuato., Conclusions: The evidence herein helps determine the population and risk factors that should be focused on in carrying out the HCV microelimination strategy of continuous screening, diagnosis, medical treatment access, and epidemiologic surveillance., (Copyright © 2024 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens., Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes)., Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc)., Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups., Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011 is an ongoing trial investigating the efficacy, safety, and dose-response of BMS-663068 in treatment-experienced, HIV-1-infected patients. Herein we present the results of the primary analysis., Methods: AI438011 is a phase 2b, randomised, active-controlled trial, at 53 hospitals and outpatient clinics across ten countries in North and South America, Europe, and Africa. Individuals with an HIV-1 RNA viral load of at least 1000 copies per mL and a BMS-626529 half-maximum inhibitory concentration lower than 100 nmol/L were randomly assigned (1:1:1:1:1) to receive either BMS-663068 at 400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily or ritonavir-boosted atazanavir (300 mg of atazanavir and 100 mg of ritonavir once daily), each with 400 mg of raltegravir twice daily and 300 mg of tenofovir disoproxil fumarate once daily as a backbone. The sponsor, participants, and investigators were masked for BMS-663068 dose but not for allocation. Primary endpoints were the proportion of patients with an HIV-1 RNA viral load less than 50 copies per mL (response rate) at week 24 and the frequency of serious adverse events and adverse events leading to discontinuation, up to the week 24 analysis. The primary analyses included all patients who received at least one dose of study drug (modified intention-to-treat population). This study is registered at ClinicalTrials.gov, NCT01384734., Findings: Between July 26, 2011, and July 16, 2012, 581 participants were assessed for eligibility. Of these, 254 patients were randomly assigned to receive either BMS-663068 (n=52 for the 400 mg twice daily group, n=50 for the 800 mg twice daily group, n=51 for the 600 mg once daily group, and n=50 for the 1200 mg once daily group) or ritonavir-boosted atazanavir (n=51). 200 patients received at least one dose of BMS-663068, and 51 patients received at least one dose of ritonavir-boosted atazanavir. At week 24, 40 (80%) of 50 patients in the BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%) of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir-boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200 patients in the BMS-663068 groups and five (10%) of the 51 patients in the ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS-663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir group discontinued because of adverse events. No serious adverse events or adverse events leading to discontinuation were BMS-663068-related. Grade 2-4 adverse events related to study drug(s) occurred in 17 (9%) of 200 patients across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted atazanavir group. For the BMS-663068 groups these events were mostly single instances with no dose relation and for the ritonavir-boosted atazanavir group these were mostly gastrointestinal or hepatobiliary disorders associated with hyperbilirubinaemia., Interpretation: In a comparison with ritonavir-boosted atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis support continued development of BMS-663068, which is being assessed in a phase 3 trial in heavily treatment-experienced individuals., Funding: Bristol-Myers Squibb., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is a Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose-response of BMS-663068 versus atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive subjects., Materials and Methods: Antiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (BMS-626529 IC50 100 nM), were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control group (ATV/r 300/100 mg QD) with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). A sub-group analysis of viral efficacy and immunologic reconstitution is presented., Results: A total of 251 subjects were treated. Median age was 39 years, 60% were male and 38% were white. Median baseline (BL) viral load (VL) was 4.85 log10 c/mL (43%; 100,000 c/mL) and median CD4+ T-cell count was 230 cells/mm(3) (38%; 200 CD4 cells/mm(3)). Through Week 24, response rates (HIV-1 RNA 50 c/mL) were comparable across all BMS-663068 arms and the ATV/r arm regardless of gender, age and race. Response rates for subjects with BL VL 100,000 c/mL (BMS-663068, 82-96%; ATV/r, 93%) were higher than those for subjects with BL VL ≥100,000 c/mL (BMS-663068, 70-87%; ATV/r, 73%); however, there were no substantial differences in response across the BMS-663068 and ATV/r arms in either sub-group. Response rates for subjects with BL CD4+ cell counts ≥200 cells/mm(3) (87-96%) were higher than those for subjects with BL CD4+ cell counts 200 cells/mm(3) (62-82%); however, no substantial differences in response were seen across the BMS-663068 and ATV/r arms in either sub-group. Mean changes in CD4+ T-cell counts from BL were similar across all arms regardless of gender, age and BL CD4+ T-cell count., Conclusion: Virologic response rates were similar across the BMS-663068 and ATV/r arms in TE subjects, regardless of BL demographic characteristics (gender, race, age), BL HIV-1 RNA, or BL CD4+ T-cell count. Mean increases in CD4+ T-cell counts across the BMS-663068 arms were consistent with ATV/r, regardless of gender, age and BL CD4+ T-cell count. These results support continued development of BMS-663068. Note: Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.

Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is an ongoing, Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose-response of BMS-663068 vs. atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive subjects. At Week 24, response rates across the BMS-663068 arms were consistent with ATV/r., Materials and Methods: Antiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (including BMS-626529 IC50 100 nM) were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control arm (ATV/r 300/100 mg QD), with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). The complete safety profile through Week 24 is reported., Results: In total, 251 subjects were treated (BMS-663068, 200; ATV/r, 51). No BMS-663068-related adverse events (AEs) led to discontinuation. Grade 2-4 drug-related AEs occurred in 17/200 (8.5%) subjects across the BMS-633068 arms; however, these events were mostly single instances and no dose-relationship was seen. Similarly, no noticeable trend for Grade 3-4 laboratory abnormalities was seen and Grade 3-4 hematologic changes and liver chemistry elevations were uncommon (neutropenia, 2.5%; AST/ALT elevations, 1% (n=196)). In the ATV/r arm, Grade 2-4 drug-related AEs occurred in 14/51 (27.5%) subjects and were mostly secondary to gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs) occurred in 13/200 (6.5%) and 5/51 (9.8%) subjects receiving BMS-663068 and ATV/r, respectively; most were secondary to infections and none were related to study drugs. The most common AE reported for BMS-663068 was headache (28/200, 14%), occurring in 5/51 (10%) subjects in the ATV/r arm; in the BMS-663068 arms, this was not dose-related. There were no deaths., Conclusions: BMS-663068 was generally well tolerated across all arms, with no related SAEs or AEs leading to discontinuation and no dose-related safety signals. There were no trends for Grade 2-4 AEs or clinical laboratory abnormalities. These results support continued development of BMS-663068. Note: Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.

Thrombosis has been considered an uncommon complication in patients with AIDS. In a 42-month period, 28 adult male homosexuals with AIDS experienced 34 thrombotic events. All but three received HAART regimen, two a successful round of double nucleoside analog therapy, and one patient received no treatment. Median age of group was 38.5 years (range, 24 to 56 years). Median time from HIV infection to thrombosis was 40.5 months (range, 3 to 108 months). No patient had previous thrombosis, family history of thrombosis, or prothrombotic conditions. There were 31 deep vein thromboses, two pulmonary thromboembolisms, and one renal vein thrombosis. Six patients had two thrombotic events. The rate of thrombosis during the 42-month study period was 1.52% (cumulative incidence = 0.30%/year), while the rate of thrombosis in 600 patients before the era of protease inhibitor therapy was 0.33% (cumulative incidence approximately 0.055%/year) (p < 0.001). Due to high incidence of thrombotic recurrences and hemorrhagic complications while using oral anticoagulants, acetylsalicylic acid was initiated; no thrombotic episodes were recorded while using this drug. Protein C and protein S deficiency were found in nine and two patients, respectively. Two patients had lupus anticoagulant and two activated protein C resistance (APCR) without FV Leiden mutation (APCR test was negative after initial screening). Fifteen patients had no thrombophilic abnormalities. These data suggest that protease inhibitors could be a risk factor for venous thrombosis not due to thrombophilic abnormalities but likely related to abnormalities in platelets or endothelium.

The aim of this report is to describe five patients with lamivudine-induced pure red cell aplasia, an association not previously described. We describe patients with unresponsive anemia in whom a complete study including blood cell counts, reticulocyte counts, hemolysis tests, and bone marrow aspiration was performed. Pure red cell aplasia was considered when anemia was associated with normal leukocyte and platelet counts with a corrected reticulocyte count below 1% and less than 5% bone marrow erythroid progenitors in the absence of positive hemolysis tests. Complete remission was considered when bone marrow erythroid progenitors were at least 16%. Five male patients had pure red cell aplasia with a median age of 32 years (range 29 to 37 years). Before lamivudine, they had hemoglobin >11.8 g/dl without transfusion requirements. After receiving the drug, hemoglobin dropped to 5.2 g/dl (4.3 to 6.1 g/dl) with high transfusion requirements and mean bone marrow erythroid progenitors of 1.84% (0 to 4%). Withdrawal of lamivudine was attempted to confirm the diagnosis. Seven weeks after stopping lamivudine, hemoglobin rose up to 12.8 g/dl (11 .3 to 13.8 g/dl) and bone marrow erythroid progenitors increased up to 25.6% (21 to 40%) without transfusion requirements. Lamivudine-induced pure red cell aplasia may be a cause of anemia unresponsive to conventional treatment in AIDS. Since lamivudine use in Mexico has been relatively short, we expect more cases to appear in the future.

Two cases of diabetic patients with normal TCD4+ cell count with chronic diarrhoea and Cryptosporidium are described herein. In both cases serologic tests for HIV were negative. The fact that these patients developed a pathology usually seen in presence of low TCD4+ cell counts suggests that some immune defect other than cellular might be involved in the pathogenesis of this infection. Authors concluded that intentional search for Cryptosporidium should be considered in the study of the diabetic patient with chronic diarrhoea.

Sera from 19 patients with hypersensitivity pneumonitis induced by avian antigens were studied in order to determine the presence of circulating autoantibodies. IgM and IgG rheumatoid factors were positive in 68% and 100% of the cases respectively. IgM-rheumatoid factor was detected with at least two methods, showing titers between 1:20 and 1:1280 by the latex agglutination test and between 140 and 579 IU/ml by nephelometry test. The IgG rheumatoid factor was studied by the indirect immunofluorescence technique, showing positive determinations in all of our hypersensitivity pneumonitis patients. Titers of these autoantibodies ranged from 1:80 to 1:640. In addition, we studied the presence of antinuclear, anti-nDNA, anti-mitochondrial, and anti-smooth muscle antibodies by the immunofluorescence test using HEp-2 cells, mouse kidney, and Crithidia luciliae targets. Sera from all of our hypersensitivity pneumonitis patients have negative results of autoantibodies to these antigens. Negative results of autoantibodies to the nRNP, Sm, SS-A(Ro) and SS-B(La) nuclear antigens by counterimmuno-electrophoresis and double immunodiffusion techniques were also obtained. As controls we studied 14 healthy individuals and 8 subjects exposed to avian antigens but without hypersensitivity pneumonitis symptoms and no positive determinations for rheumatoid factor, antinuclear antibodies, as well as to anti-mitochondrial and anti-smooth muscle antibodies, were found. These findings support that different immune abnormalities are present in patients with hypersensitivity pneumonitis induced by avian antigens. One of these immune alterations or a combination of them may promote or facilitate the acute interstitial lung injury and/or perpetuate a chronic inflammatory process.

Twenty five patients with juvenile rheumatoid arthritis were studied in order to define the frequency and kind of circulating autoantibodies in this entity, as well as, their relationship with the different disease subgroups and complications. Also the association of these autoantibodies with the activity stage of the illness was determined. There were 14 pauciarticular, 8 polyarticular and 3 systemic juvenile rheumatoid arthritis patients. Twelve have a flare of the disease and 13 were completely asymptomatic. Rheumatoid factor measured by the latex agglutination tests was positive in 6 children. These included 2 patients with pauciarticular disease, showing titers below 1:40 and 4 cases with polyarticular disease, showing titers above 1:320. One of these last patients developed and adult type rheumatoid arthritis during her evolution and was treated with D-penicillamine. The polyarticular but not the pauciarticular patients showed positive tests for rheumatoid factor by nephelometry. No definite association between these laboratory results and the activity of the disease was noted. Positive antinuclear antibodies by the indirect immunofluorescence test were found in 3 pauciarticular and one polyarticular patients. A predominant homogeneous staining was found with the mouse kidney substrate, whereas homogeneous and speckled patterns were noted with the homologous HEp-2 cells. One patient with persistent positive antinuclear antibodies revealed uveitis. Three of the 4 sera with positive antibodies by the indirect immunofluorescent test have also anti-nucleoprotein antibodies by the hemagglutination test with titers above 1:32.(ABSTRACT TRUNCATED AT 250 WORDS)

The coexistence of gout and rheumatoid arthritis is described in a patient who was followed for 7 years before the association was established. This is the 4th non-Caucasian patient recorded in the literature. He was HLA-DR4 positive, and no data suggestive of a predisposition to gout were found. Interestingly, during followup rheumatoid and gouty phases alternated, without simultaneous manifestations of both diseases.