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PURPOSE OF REVIEW: The purpose of this review is to use the currently available clinical and epidemiological data, to identify key aspects to improve both the clinical management and public health response to SARS-CoV-2/HIV co-infection among HIV vulnerable populations and people living with HIV (PLWH). RECENT FINDINGS: While at the beginning of the COVID-19 pandemic, the lack of robust information on SARS-CoV-2/HIV co-infection, prevented a clear picture of the synergies between them, currently available data strongly support the importance of common structural factors on both the acquisition and clinical impact of these infections and the relevance of age, comorbidities, and detectable HIV viral load as associated worse prognostic factors among PLWH. Although more information is needed to better understand the biological, clinical, and epidemiological relationship between both infections, a syndemic approach to prevent SARS-CoV-2 among HIV high-risk groups and PLWH, targeting these populations for SARS-CoV-2 vaccines and protocolizing early identification of PLWH with worse COVID-19 prognosis factors, is crucial strategies to decrease the overall impact of SARS-CoV-2 /HIV co-infection.
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COVID-19 , Coinfección , Infecciones por VIH , COVID-19/epidemiología , Vacunas contra la COVID-19 , Coinfección/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Pandemias , Salud Pública , SARS-CoV-2RESUMEN
Single-tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high-income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV-related neurological disease, or associated opportunistic infections, which include co-infections, and primarily age- and lifestyle-related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR - bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) - in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co-infection; HLA-B*5701 status; drug-drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence-friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non-inferior to dolutegravir-based regimens previously recommended by most guidelines for treatment initiation in large double-blind, randomised clinical trials in treatment-naïve or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.
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Adenina/análogos & derivados , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Tenofovir/efectos adversos , Adenina/efectos adversos , Adenina/uso terapéutico , Alanina , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Comorbilidad , Combinación de Medicamentos , Emtricitabina , Estudios de Equivalencia como Asunto , Infecciones por VIH/sangre , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Humanos , Piperazinas , Piridonas , Factores de Riesgo , Factores Socioeconómicos , Comprimidos , Tenofovir/uso terapéuticoRESUMEN
OBJECTIVES: We aimed to determine the fraction of HIV-diagnosed individuals who had primary health care (PHC) contacts 3 years prior to HIV diagnosis and whether the risk of HIV diagnosis and degree of immunodeficiency were associated with the frequency of visits or procedures performed. METHODS: We used data from national registries to conduct a population-based nested case-control study. Cases were individuals diagnosed with HIV infection in Denmark from 1998 to 2016. Population controls were extracted from the general population matched 13:1 on gender and age. We used conditional logistic regression. As there was a statistically significant interaction, analyses were further stratified by gender and Danish/non-Danish origin. RESULTS: We identified 2784 cases and 36 192 controls. Ninety-three per cent of cases and 88% of controls attended PHC at least once in the 3 years prior to diagnosis, with a higher median number of visits to PHC (NVPC) for cases. We found a statistically significant positive association between NVPC and risk of subsequent HIV diagnosis in men and non-Danish women. A U-shaped association between NVPC and risk of HIV diagnosis among Danish women. No substantial association between NVPC and degree of immunodeficiency was found. Risk of HIV diagnosis and degree of immunodeficiency were weakly associated with type of procedures performed. CONCLUSIONS: For most HIV-infected individuals, there seem to be many opportunities for earlier diagnosis in PHC. In men and non-Danish women, the risk of HIV diagnosis but not the degree of immunodeficiency was related to NVPC. The results suggest that the type of medical procedure performed cannot not be used as a guide by the primary physician to indicate which patients to test.
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Diagnóstico Precoz , Infecciones por VIH/diagnóstico , Atención Primaria de Salud/métodos , Adulto , Estudios de Casos y Controles , Dinamarca , Femenino , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The aim of the study was to assess the regression of liver stiffness after successful direct-acting antiviral (DAA) treatment in patients with hepatitis C virus (HCV) monoinfection and HCV/-HIV coinfection. In addition, we aimed to identify factors associated with liver stiffness regression. METHODS: We studied patients treated with interferon-free DAA regimens with a sustained virological response at week 12 (SVR12 ) or 24 (SVR24 ) post-treatment. Liver stiffness was assessed by transient elastography (TE) before the initiation and after the end of treatment (median 12 weeks). RESULTS: Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8 kPa [interquartile range (IQR) 5.9-12.0 kPa] in mono-infected patients and 10.7 kPa (IQR 7.8-17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8 kPa (n = 214; P < 0.0001). There was no difference between mono- and coinfected patients (-2.2 versus -3.3 kPa, respectively; P = 0.88), which was verified by an analysis of covariance (ANCOVA) adjusting for baseline TE values. Significant (≥ 30%) regression of liver stiffness was achieved by 45% of patients (54% with baseline TE ≥ 7.1 kPa). In multivariate analysis, a prior HCV treatment was a negative predictor of liver stiffness regression [odds ratio (OR) 0.31; P = 0.001]. A higher baseline TE value was positively associated with achieving a significant regression (OR 1.06; P = 0.02). HIV coinfection status, HCV genotype, age, sex, treatment duration, controlled attenuation parameter value, bilirubin concentration, platelet count and aspartate aminotransferase concentration were not associated with liver stiffness regression. CONCLUSIONS: Regression of liver stiffness after successful DAA treatment did not differ in patients with HCV monoinfection and those with HCV/HIV coinfection. Half of all patients achieved a significant (≥ 30%) regression. Prior treatment for HCV was a negative predictor for this endpoint, while a higher baseline TE value was positively associated with regression.
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Antivirales/uso terapéutico , Infecciones por VIH/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hígado/diagnóstico por imagen , Adulto , Diagnóstico por Imagen de Elasticidad , Femenino , Infecciones por VIH/diagnóstico por imagen , Hepatitis C Crónica/diagnóstico por imagen , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. METHODS: A population-based, prospective, multicentre cohort study was carried out. Treatment-naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. RESULTS: A total of 4165 subjects (37% treatment-naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. CONCLUSIONS: In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
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Cobicistat/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Quinolonas/efectos adversos , Raltegravir Potásico/efectos adversos , Adulto , Recuento de Linfocito CD4 , Cobicistat/administración & dosificación , Femenino , Infecciones por VIH/inmunología , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Piridonas , Quinolonas/administración & dosificación , Raltegravir Potásico/administración & dosificación , EspañaRESUMEN
Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, "NRTI-reducing" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI-sparing strategies, for example an integrase strand transfer inhibitor (INSTI) plus a ritonavir-boosted protease inhibitor (PI/r) or PI/r + lamivudine (3TC), in both naïve and switch regimes. Of 10 key studies in treatment-naïve adults assessing five NRTI-reducing strategies, only four studies demonstrated noninferiority vs. SOC [GARDEL, NEAT 001, AIDS Clinical Trials Group 5142 and PROGRESS]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI-reducing arm was shown in six of 10 studies (ATLAS-M, SALT, DUAL, OLE, LATTE-2 and SWORD). In general, NRTI-reducing therapy did not always result in an improvement in short- or long-term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI-reducing strategies has been compared against a single-pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety/tolerability, and a favourable cost-efficacy ratio, preferably in a single pill, will eventually match the current SOC of triple ARV therapy.
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Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Nucleósidos/administración & dosificación , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Utilización de Medicamentos , Humanos , Nucleósidos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Transcriptasa Inversa/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.
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Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Adolescente , Adulto , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/inmunología , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1 , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/µL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.
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Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Adulto , Antirretrovirales/administración & dosificación , Europa (Continente) , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Pruebas PsicológicasRESUMEN
OBJECTIVES: HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use of resistance testing in START trial participants. METHODS: In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. RESULTS: Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1.8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, the prevalence of TDR was highest in Australia (17.5%), France (16.7%), the USA (12.6%) and Spain (12.6%). No participant characteristics were identified as predictors of the presence of TDR. CONCLUSIONS: START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the USA and Australia, TDR prevalence rates varied by country.
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Transmisión de Enfermedad Infecciosa , Farmacorresistencia Viral , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Genotipo , Técnicas de Genotipaje , VIH-1/clasificación , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. METHODS: A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). RESULTS: A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). CONCLUSIONS: The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.
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Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Enfermedades del Sistema Nervioso Central/inducido químicamente , Sustitución de Medicamentos , Infecciones por VIH/tratamiento farmacológico , Trastornos Mentales/inducido químicamente , Nevirapina/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Anciano , Alquinos , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Ciclopropanos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Estudios Prospectivos , Calidad de VidaRESUMEN
With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population. The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking), toxicities associated with cumulative exposure to some antiretroviral agents, together with persistent chronic inflammation, and immune activation associated with HIV infection. Tools are available to calculate an individual's predicted risk of CVD and should be incorporated in the regular follow-up of HIV-infected patients. Targeted interventions to reduce this risk must be recommended, including life-style changes and medical interventions that might include changes in antiretroviral therapy.
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Envejecimiento , Enfermedades Cardiovasculares/complicaciones , Infecciones por VIH/complicaciones , Enfermedades Cardiovasculares/epidemiología , Europa (Continente)/epidemiología , Infecciones por VIH/epidemiología , Humanos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: In highly endemic areas, up to 20 % of human immunodeficiency virus (HIV)-infected persons will develop progressive disseminated histoplasmosis (PDH). Europe is not endemic to histoplasmosis, and the disease is mainly found in immigrants often co-infected with HIV. METHODS: We present a case of a patient with HIV and PDH highlighting the possible diagnostic difficulties that may arise in a non-endemic area and review the literature of histoplasmosis in the context of HIV infection with special focus on Europe. DISCUSSION: When cellular immunity wanes (usually at CD4 T-lymphocyte counts <150 cells/µL) histoplasma infection, acquired earlier, can reactivate and disseminate. PDH is an acquired immune deficiency syndrome(AIDS)-defining disease and a life-threatening infection, with a clinical spectrum ranging from an acute, fatal course with lung infiltrates and respiratory failure, shock, coagulopathy and multi-organ failure, to a more subacute disease with focal organ involvement, pancytopenia and hepatosplenomegaly. Mortality rates remain high for untreated patients, but early diagnosis, proper antifungal treatment and early initiation of antiretroviral therapy have improved the prognosis. CONCLUSION: European infectious diseases physicians, microbiologists and pathologists must be aware of histoplasmosis, particularly when facing HIV-infected immigrants from endemic areas. This is increasingly important due to migration and travel activities from these areas.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Europa (Continente)/epidemiología , Histoplasmosis/epidemiología , Histoplasmosis/patología , Humanos , Masculino , Análisis de SupervivenciaRESUMEN
BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. METHODS: Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL)â ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). RESULTS: Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/µL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. CONCLUSIONS: We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.
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Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) caused by serovars L1-L3 of Chlamydia trachomatis. Rare in the western world prior to 2003, different outbreaks or clusters of LGV have been reported in Europe, North America and Australia among men who have sex with men (MSM) over the past few years. The majority were HIV infected MSM with high-risk sexual behaviour and a high rate of concomitant STD, including hepatitis C. Most of them presented with a proctitis syndrome and only a few with the classical bubonic form. A previously non-described serovar, L2b, has been identified as the main causative agent of the epidemic. A delay in diagnosis has been the rule because of the misleading symptomatology of LGV proctitis, the unfamiliarity of the disease to physicians, and the lack of a routine diagnostic test for LGV serovars. It is crucial to increase the awareness of the disease among physicians for prompt diagnosis and treatment, to avoid complications, and to stop ongoing transmission. It has additional public health implications since LGV may facilitate the transmission and acquisition of HIV and other STD.
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Chlamydia trachomatis/aislamiento & purificación , Enfermedades Endémicas , Linfogranuloma Venéreo/complicaciones , Linfogranuloma Venéreo/epidemiología , Proctocolitis/epidemiología , Proctocolitis/microbiología , Australia/epidemiología , Comorbilidad , Países Desarrollados , Europa (Continente)/epidemiología , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Homosexualidad Masculina , Humanos , Masculino , América del Norte/epidemiologíaRESUMEN
OBJECTIVES: To evaluate the expected activity of etravirine in clinical samples, according to mutational patterns associated with decreased virological response (VR). METHODS: We identified 1586 routine clinical samples with resistance-associated mutations (RAMs) to nevirapine and efavirenz (K103N 60%, Y181C 37%, G190A 27%, V108I 13%). Concerning in vitro identified etravirine mutations, samples with F227C, Y181I, M230L or L100I plus K103N plus Y181C were considered highly resistant. Samples with two RAMs plus Y181C or V179D or K101E or Y188L were considered intermediate. The prevalence of 13 RAMs recently associated with decreased VR to etravirine in the DUET clinical trials was also investigated. RESULTS: Most samples (69%) harboured more than one IAS-USA RAM to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): 42% harboured two RAMs, 21% three RAMs and 6% four or more RAMs. The prevalence of 13 specific etravirine RAMs was V179F 0.12%, G190S 3.9%, Y181V 0.1%, V106I 2.6%, V179D 1.6%, K101P 2.0%, K101E 10.1%, Y181C 36.9%, A98G 5.9%, V90I 6.9%, Y181I 3.6%, G190A 27% and L100I 9.1%. The five RAMs with the most impact on VR (V179F/D, G190S, Y181V and V106I) occurred less often. Overall, 8.2% of the samples had three or more etravirine RAMs and only 1.1% had four or more. In addition, patterns of RAMs previously associated with intermediate etravirine resistance were present in 26.2% of the samples, whereas 4.85% displayed patterns of high-degree resistance. CONCLUSIONS: For RAMs associated with decreased VR, etravirine resistance in routine clinical samples was lower than previously reported. High-degree resistance was uncommon, even in patients with resistance to first-generation NNRTIs, whereas low-to-intermediate etravirine resistance was more common.
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Fármacos Anti-VIH/farmacología , Benzoxazinas/farmacología , Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Mutación Missense , Nevirapina/farmacología , Piridazinas/farmacología , Alquinos , Ciclopropanos , VIH-1/genética , Humanos , Nitrilos , PirimidinasRESUMEN
OBJECTIVES: To evaluate the safety, immunological outcome and HIV-1 evolution in the reverse transcriptase (RT) in patients with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF). METHODS: Pilot analysis of highly experienced patients (n=28), with > or =1 thymidine-associated mutation (TAM) and the M184V mutation. RESULTS: Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/microL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (P<0.001), with 35.7% (10/28) achieving a VL of <50 copies/mL. The median 24-week decrease in CD4 was -53 cells/microL and only-17 cells/microL when baseline CD4 was <350 cells/microL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VL<400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL<10,000 copies/mL (P=0.01). CONCLUSIONS: A bridging regimen with TZV+TDF prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication.
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Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral Múltiple/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/genética , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adenina/análogos & derivados , Adenina/uso terapéutico , Adulto , Fármacos Anti-VIH/farmacología , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Didesoxinucleósidos/uso terapéutico , Farmacorresistencia Viral Múltiple/genética , Femenino , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Organofosfonatos/uso terapéutico , Proyectos Piloto , ARN Viral/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Tenofovir , Timidina/genética , Carga Viral , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: We determined whether coformulated zidovudine/lamivudine/abacavir plus tenofovir could maintain immune status in comparison with a genotype-guided salvage regimen in highly pretreated patients. METHOD: This was a randomized pilot control-arm study. The primary endpoint was the proportion of patients who maintained their CD4+ T-cell count at Week 48. RESULTS: Thirteen patients were randomized to the study arm and 10 to the control arm. At 48 weeks, 8 (64%) patients in the study arm and 10 (100%) in the control arm maintained their immune status (p = .09). No new AIDS-defining events occurred. Three patients (27%) in the study arm and 5 (50%) in the control arm achieved an undetectable viral load (p = .39). When a fully suppressive regimen was initiated, 69% of patients in the study arm (9 patients) and 60% (6 patients) in the control arm reached <50 copies at 96 weeks (p = .98). CONCLUSION: Although no statistically significant differences in immunological course were observed between the arms, the control group achieved better results after 48 weeks. This transient therapy could be reserved for specific patients in whom the risk of incomplete adherence or toxicity compromises efficacy while they are awaiting a fully active drug, without jeopardizing viral efficacy when a fully suppressive regimen is initiated.
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Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Esquema de Medicación , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proyectos Piloto , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Resultado del Tratamiento , Carga ViralRESUMEN
PURPOSE: The aim of the study was to assess differences in health-related quality of life (HRQoL) in HIV-infected naive patients treated with two HAART regimens at 12 months. METHOD: The MOS-HIV questionnaire was used to measure HRQoL in a subgroup of 127 patients included in the COMBINE study, which was an open-label, randomized, multicenter study comparing zidovudine (ZDV) and lamivudine (3TC) plus nelfinavir (NFV) or nevirapine (NVP) regimens in HIV-infected naive patients. 63 patients were included in the ZDV/3TC/NFV arm and 64 in the ZDV/3TC/NVP arm. RESULTS: No statistically significant differences were observed at baseline in demographic and clinical variables and HRQoL scores between treatment groups, except that the proportion of homosexual men was higher in the ZDV/3TC/NVP arm. There were no statistically significant differences in HRQoL scores between arms at 12 months and over time; only ZDV/3TC/NVP patients showed statistically significant improvement in Physical Health Summary score (p <.01) and a trend toward a better profile in Mental Health Summary score (p =.07). Overall, patients who were treated with ZDV/3TC/NVP showed greater changes in physical dimensions and patients who were treated with ZDV/3TC/NFV showed greater changes in mental health. CONCLUSION: Differences in HRQoL between study groups at 1 year follow-up were not detected. Nevertheless, a trend toward improvement was observed in summary health scores in ZDV/3TC/NVP-treated patients.