[Medical Care of people living with HIV in the Instituto Mexicano del Seguro Social]. / Atención a personas que viven con el VIH en el IMSS.

Infection by the human immunodeficiency virus (HIV) is apublic health problem worldwide, however, the incidence has remained relatively stable. In Mexico, around 10,000 new cases are reported each year. The Instituto Mexicano del Seguro Social (IMSS) has been a pioneer in the care of people living with HIV (PLWHA), gradually incorporating the different antiretroviral drugs (ARV). The first ARV used at the institutional level was zidovudine, in the 1990s, and later other agents were incorporated, such as protease inhibitors, drugs from the group of non-nucleoside analogs, and integrase inhibitors. In 2020, the migration to ARV schemes coformulated in a single tablet based on integrase inhibitors, which constitute a highly effective option and timely supply of drugs has been achieved in 99% of the population. In the aspect of prevention, the IMSS has also been a pioneer by being the first institution to implement HIV pre-exposure prophylaxis in 2021 at the national level and since 2022 universal post-exposure prophylaxis is available. The IMSS continues to be at the forefront incorporating the use of different management tools and instruments for the benefit of the population living with HIV. This document summarizes the history of HIV in the IMSS from the beginning of the epidemic to the present time.

La infección por el virus de la inmunodeficiencia humana (VIH) es un problema de salud pública a nivel mundial, sin embargo, la incidencia ha permanecido relativamente estable. En México se informa de alrededor de 10,000 casos nuevos al año. El Instituto Mexicano del Seguro Social (IMSS) ha sido pionero en la atención a las personas que viven con el VIH (PVV), incorporando paulatinamente los diferentes medicamentos antirretrovirales (ARV). El primer ARV utilizado a nivel institucional fue la zidovudina, en la década de los noventa, y posteriormente fueron incorporados otros agentes como los inhibidores de la proteasa, los medicamentos del grupo de los análogos no nucleósidos y los inhibidores de la integrasa. En el año 2020 ocurrió la migración a esquemas de ARV coformulados en una sola tableta a base de inhibidores de la integrasa, que constituyen una opción de alta eficacia y se ha logrado el surtimiento oportuno de los fármacos en el 99% de la población. En el aspecto de la prevención, el IMSS también ha sido pionero al ser la primera institución en implementar la profilaxis preexposición de VIH en el año 2021 a nivel nacional y desde el año 2022 se dispone de la profilaxis postexposición universal. El IMSS continúa a la vanguardia incorporando el uso de diferentes herramientas e instrumentos de gestión para beneficio de la población que vive con el VIH. En el presente documento se sintetiza la historia del VIH en el IMSS desde los inicios de la epidemia hasta el momento actual.

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1.

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.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.

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.

HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 sub-group analysis.

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.

Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 analysis.

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.

Effect of highly active antiretroviral therapy on homocysteine plasma concentrations in HIV-1-infected patients.

OBJECTIVE: To analyze the effect of antiretroviral therapy on homocysteine levels in HIV-1-infected patients. DESIGN: Observational, prospective study of patients with AIDS. METHODS: We included patients with HIV-1 infection naive for antiretroviral drugs. Before and after 6 months of treatment, we evaluated fasting and postoral methionine load plasma homocysteine, serum vitamins B6 and B12, and intraerythrocyte folate levels. RESULTS: We studied 69 patients who began therapy for a 6-month period. Fasting and postoral methionine load plasma homocysteine levels increased significantly after 6 months of antiretroviral therapy with respect to basal values (P < 0.001). Fasting hyperhomocysteinemia was present in 7.3% of patients before treatment and in 89.9% after 6 months of therapy (P = 0.0001). Postoral methionine load hyperhomocysteinemia was found in 4.5% of subjects before therapy vs. 98.5% at the end of study period (P = 0.001). These results were not associated with folate or vitamins B6 or B12 levels. CONCLUSIONS: In patients with HIV-1 infection, fasting and postoral methionine load plasma homocysteine levels increased after 6 months of antiretroviral treatment. Nutritional abnormalities were not responsible for hyperhomocysteinemia, suggesting that enzymatic disturbances in the metabolic pathways of homocysteine may occur.

Effect of combined administration of clopidogrel and lysine acetylsalicylate versus clopidogrel and aspirin on platelet aggregation and activated GPIIb/IIIa expression in healthy volunteers.

Platelet activation contributes to thrombotic events in cardiovascular disease. Acetylsalicylic acid (ASA) is used in combination with clopidogrel to reduce cardiovascular events. Lysine acetylsalicylate (L-ASA), also inhibits platelet activation with fewer gastrointestinal side effects than ASA. Dual therapy with L-ASA and clopidogrel may result in an antiplatelet effect with fewer side effects. We compared the antiplatelet effect of combined ASA/clopidogrel versus L-ASA/clopidogrel in healthy subjects. Fourteen volunteers (seven men and seven women, aged 25-45 years) received antiplatelet therapy during 14-day periods in the following sequence: 75 mg ASA; 160 mg L-ASA; 75 mg clopidogrel; 160 mg L-ASA plus 75 mg clopidogrel, and 75 mg ASA plus 75 mg clopidogrel. We evaluated platelet aggregation and glycoprotein IIb/IIIa activation. Our results show that administration of L-ASA/clopidogrel is as effective as ASA/clopidogrel combination.

[Clinical characteristics and follow-up of patients with AIDS and acute abdominal pain]. / Características clínicas y evolución de pacientes con SIDA y dolor abdominal agudo.

Abdominal symptoms frequently affect patients with AIDS. Acute abdominal pain is a diagnostic challenge that may require elective or urgent surgical treatment, although information about the latter is scarce. In this study we analyzed the clinical findings and follow-up of acute abdominal pain complicating patients with AIDS. In a two-year period, we collected several variables from patients with AIDS and acute abdominal pain: demographic, laboratory, clinical symptoms, initial diagnosis, surgical findings, post-surgical and histopathological diagnosis and post-surgical complications. From 232 hospitalized patients, 34 had acute abdominal pain: 32 male and 2 women (median age = 32 years; range 26 to 58 years). Twenty-two patients required surgical treatment. Eight patients had a post-surgical complication; in five of them, six surgical re-interventions were performed. Three deaths occurred in the 30-day period after surgery. Survival for patients conservatively treated was 4 months (1 to 17 months), vs. 6.5 months (1 to 20 months) in the surgically treated group. Physicians should be aware about the several diagnostic possibilities of acute abdominal pain complicating patients with AIDS. Delay of surgery in these patients may be lethal. Surgery has an important role in the integral treatment of patients with AIDS.

Características clínicas y evolución de pacientes con SIDA y dolor abdominal agudo / Clinical characteristics and follow-up of patients with AIDS and acute abdominal pain

Los síntomas abdominales son frecuentes en el SIDA y el dolor abdominal es un reto diagnóstico que puede requerir cirugía electiva o urgente aunque la información acerca de esta última es pobre. En este estudio analizamos los hallazgos clínicos y evolución de pacientes con SIDA y dolor abdominal agudo. En un periodo de dos años, recolectamos variables demográficas y de laboratorio, síntomas clínicos, diagnóstico inicial, hallazgos quirúrgicos, diagnóstico postquirúrgico, hallazgos histopatológicos y complicaciones postoperatorias de pacientes con SIDA y dolor abdominal agudo. De 232 pacientes hospitalizados, 34 tuvieron dolor abdominal agudo: 32 hombres y 2 mujeres (mediana de edad = 32 años; intervalos 26 a 58). Veintidós pacientes requirieron manejo quirúrgico. Ocho pacientes presentaron complicaciones postquirúrgicas; cinco requirieron seis segundas intervenciones. Ocurrieron tres muertes en los 30 días luego de la cirugía inicial. La supervivencia para los pacientes tratados médicamente fue 4 meses (1 a 17), contra 6.5 meses (1 a 20) del grupo quirúrgico. El médico debe estar alerta acerca de las posibilidades diagnósticas del enfermo con SIDA y dolor abdominal agudo. Demorar la cirugía puede ser letal. La cirugía tiene un papel importante en el tratamiento integral del paciente con SIDA.

Abdominal symptoms frequently affect patients with AIDS. Acute abdominal pain is a diagnostic challenge that may require elective or urgent surgical treatment, although information about the latter is scarce. In this study we analyzed the clinical findings and follow up of acute abdominal pain complicating patients with AIDS. In a two-year period, we collected several variables from patients with AIDS and acute abdominal pain: demographic, laboratory, clinical symptoms, initial diagnosis, surgical findings, post surgical and histopathological diagnosis and post surgical complications. From 232 hospitalized patients, 34 had acute abdominal pain: 32 male and 2 women (median age = 32 years; range 26 to 58 years). Twenty-two patients required surgical treatment. Eight patients had a post surgical complication; in five of them, six surgical re interventions were performed. Three deaths occurred in the 30 day period after surgery. Survival for patients conservatively treated was 4 months (1 to 17 months), vs. 6.5 months (1 to 20 months) in the surgically treated group. Physicians should be aware about the several diagnostic possibilities of acute abdominal pain complicating patients with AIDS. Delay of surgery in these patients may be lethal. Surgery has an important role in the integral treatment of patients with AIDS.

Venous thrombosis among patients with AIDS.

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.

Diarrea crónica y Cryptosporidium en pacientes diabéticos con subpoblación linfocitaria normal: informe de dos casos / Chronic diarrhea and Cryptosporidium in diabetic patients with normal lymphocyte subset counts: report of two cases

Se describen dos casos de pacientes diabéticos con cuentas normales de linfocitos TCD4+, que presentaban diarrea crónica y en los cuales se detectó Cryptosporidium en heces. En ambos casos las pruebas serológicas para VIH resultaron negativas. El hecho de que estos pacientes desarrollaran una patología que se observa comunmente en presencia de cuentas bajas de linfocitos TCD4+, sugiere que una alteración inmunológica distinta de la celular pudiera estar involucrada en la patogénesis de esta infección. Los autores sugieren que la búsqueda intencionada de Cryptosporidium debe considerarse en el estudio de la diarrea crónica del paciente diabético