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OBJECTIVES: To describe HIV care outcomes in people of Black ethnicities living in England during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic. METHODS: This was an observational cohort study of people of self-reported Black ethnicities attending for HIV care at nine HIV clinics across England. The primary outcome was a composite of antiretroviral therapy (ART) interruption and HIV viraemia (HIV RNA ≥200 copies/mL) ascertained via self-completed questionnaires and review of medical records. We used multivariable logistic regression to explore associations between ART interruption/HIV viraemia and demographic factors, pre-pandemic HIV immunovirological control, comorbidity status, and COVID-19 disease and vaccination status. RESULTS: We included 2290 people (median age 49.3 years; 56% female; median CD4 cell count 555 cells/mm3; 92% pre-pandemic HIV RNA <200 copies/mL), of whom 302 (13%) reported one or more ART interruption, 312 (14%) had documented HIV viraemia ≥200 copies/mL, and 401 (18%) experienced the composite endpoint of ART interruption/HIV viraemia. In multivariable analysis, a pre-pandemic HIV RNA <200 copies/mL (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.15-0.30) and being vaccinated against SARS-CoV-2 (OR 0.41; 95% CI 0.30-0.55) were associated with reduced odds of ART interruption/HIV viraemia; pandemic-related disruptions to HIV care were common self-reported additional factors. CONCLUSIONS: During the COVID-19 pandemic, one in six people of Black ethnicities in this HIV cohort experienced an ART interruption/HIV viraemia. Some of these episodes resulted from pandemic-related healthcare disruptions. Associations with suboptimal engagement in HIV care pre-pandemic and not being vaccinated against SARS-CoV-2 suggest that wider health beliefs and/or poor healthcare access may have been contributory factors.
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Población Negra , COVID-19 , Infecciones por VIH , SARS-CoV-2 , Humanos , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , Infecciones por VIH/tratamiento farmacológico , Masculino , Inglaterra/epidemiología , Persona de Mediana Edad , Adulto , Población Negra/estadística & datos numéricos , Carga Viral , Recuento de Linfocito CD4 , Estudios de Cohortes , ViremiaRESUMEN
OBJECTIVES: To describe the clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK. METHODS: We investigated the incidence and factors associated with COVID-19 in a previously established and well-characterized cohort of black people with HIV. Primary outcomes were COVID-19 acquisition and severe COVID-19 disease (requiring hospitalization and/or resulting in death). Cumulative incidence was analysed using Nelson-Aalen methods, and associations between demographic, pre-pandemic immune-virological parameters, comorbidity status and (severe) COVID-19 were identified using Cox regression analysis. RESULTS: COVID-19 status was available for 1847 (74%) of 2495 COVID-AFRICA participants (median age 49.6 years; 56% female; median CD4 cell count = 555 cells/µL; 93% HIV RNA <200 copies/mL), 573 (31%) of whom reported at least one episode of COVID-19. The cumulative incidence rates of COVID-19 and severe COVID-19 were 31.0% and 3.4%, respectively. Region of ancestry (East/Southern/Central vs. West Africa), nadir CD4 count and kidney disease were associated with COVID-19 acquisition. Diabetes mellitus [adjusted hazard ratio (aHR) = 2.39, 95% confidence interval (CI): 1.26-4.53] and kidney disease (aHR = 2.53, 95% CI: 1.26-4.53) were associated with an increased risk, and recent CD4 count >500 cells/µL (aHR = 0.49, 95% CI: 0.25-0.93) with a lower risk of severe COVID-19. CONCLUSIONS: Region of ancestry was associated with COVID-19 acquisition, and immune and comorbidity statuses were associated with COVID-19 disease severity in people of black ethnicity living with HIV in the UK.
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Población Negra , COVID-19 , Infecciones por VIH , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/etnología , Femenino , Masculino , Reino Unido/epidemiología , Persona de Mediana Edad , Infecciones por VIH/epidemiología , Infecciones por VIH/etnología , Infecciones por VIH/complicaciones , Población Negra/estadística & datos numéricos , Adulto , Incidencia , Recuento de Linfocito CD4 , Comorbilidad , Factores de RiesgoRESUMEN
Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Secondary outcomes were eGFR <90 ml/min per 1.73 m2, end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 [95% CI 1.14-2.32]), eGFR <90 ml/min per 1.73 m2 (1.50 [1.14-1.97]), and albuminuria (1.50 [1.09-2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes. Conclusion: Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.
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OBJECTIVES: To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses. DESIGN: An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom. METHODS: Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates (all cause, liver related, and AIDS related) were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort. RESULTS: Among 25â486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28-2.00) and 10.42 (5.78-18.80), respectively. HCV coinfection was significantly associated with increased all-cause (ARR 1.43, 95% CI 1.15-1.76) and liver-related mortality (ARR 6.20, 95% CI 3.31-11.60). Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63-1.83) and 0.40 (0.20-0.81), respectively. CONCLUSION: The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals.
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Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Hepatitis B/epidemiología , Hepatitis B/mortalidad , Hepatitis C/epidemiología , Hepatitis C/mortalidad , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative. METHODS: This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4(+) T-cell count of ≥200 cells/mm(3), 14 ART recipients with a CD4(+) T-cell count of 50-199 cells/mm(3), and 15 ART-naive adults with a CD4(+) T-cell count of ≥500 cells/mm(3). Subjects received 3 doses of HZ/su (50 µg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6. RESULTS: One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4(+) T cells were higher following HZ/su vaccination than after receipt of saline (P < .0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4(+) T-cell count was noted following vaccinations. CONCLUSIONS: HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults. CLINICAL TRIALS REGISTRATION: NCT01165203.
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Adyuvantes Inmunológicos/farmacología , Formación de Anticuerpos/inmunología , Infecciones por VIH/inmunología , Vacuna contra el Herpes Zóster/inmunología , Herpes Zóster/inmunología , Herpesvirus Humano 3/inmunología , Vacunas de Subunidad/inmunología , Adyuvantes Farmacéuticos/farmacología , Anticuerpos Antivirales/inmunología , Linfocitos T CD4-Positivos/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacunación/métodosRESUMEN
INTRODUCTION: The BHIVA guidelines now feature three single tablet regimens (STRs) as recommended treatments for HIV-positive people new to therapy [1]. They are popular with patients and are attractive in a number of clinical scenarios. We sought to determine how our use of STRs had developed over a three-year period, and how the decision to opt for an STR was made. METHODS: Retrospective case-note review and database interrogation of all patients starting anti-retroviral therapy (ART) from 1st March 2011 to 31st March 2014. RESULTS: 215 patients started ART. 58% (125/215) were black-African and 47% (100/215) were female. Median CD4 at baseline was 272 cells/µL (range 1-1044 cells/µL). 69 (32%) had a viral load (VL) >100,000 copies/mL. 7 individuals had evidence of transmitted drug resistance. 88 patients started an STR. Two tested positive for HLAB5701. None had a 10 year CVS risk score of >20% and 36% had a baseline VL >100,000 copies/mL. 127 patients started a non-STR regimen, 29% had a VL >100 000 copies/mL and none had an elevated CVS risk. Information regarding baseline renal function and HLAB5701 will be provided at the conference. The use of STRs increased over the three years (25% 2011-12; 57.1% 2012-13; 44% 2013-14). There was no difference in STR prescribing between men and women. In men, heterosexual male patients were more likely to be prescribed an STR than MSM males (54% versus 43%, p 0.005). In 43% (38/88) patients had indicated a preference for an STR and 32/88 expressed a preference for a particular drug. 2% (2/88) requested to be on the same treatment as a partner. In those patients who expressed an interest in a particular drug, four had received information from a friend or partner. In 33% (29/88) cases an STR was felt by the clinician to be the best option, largely based on concerns around pill-burden and adherence (31%), viral load (16%) and renal or cardiac risk (7%). CONCLUSIONS: Use of STRs is increasing. This is not driven on in our cohort by cardiovascular risk of HLAB5701 carriage but by patient and clinician preference, and to a lesser extent by higher baseline viral loads.
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INTRODUCTION: Cobicistat, a component of stribild (STB), is known to inhibit renal creatinine secretion. A detailed analysis of the renal safety profile of STB in two Phase 3b switch studies of virologically-suppressed individuals on stable therapy: STRATEGY(S)-PI (STB vs a RTV-boosted protease inhibitor [PI] with emtricitabine and tenofovir DF [FTC/TDF]); and STRATEGY(S)-NNRTI (STB versus a non-nucleoside reverse transcriptase inhibitor [NNRTI] with FTC/TDF) is herein described. MATERIALS AND METHODS: Baseline eGFR ≥70 mL/min was an inclusion criterion. The renal safety profile of STB was examined by baseline eGFR through week 48 (i.e., changes in eGFR, renal tubular laboratory abnormalities, investigator-reported renal adverse events leading to discontinuation and unreported subclinical proximal renal tubulopathy [PRT]). Subclinical PRT was defined as a confirmed serum-creatinine increase ≥0.4 mg/dL and two or three markers of renal tubular dysfunction (hypophosphatemia, normoglycemic glycosuria, proteinuria) occurring at the same visit at least once and with no alternative etiologies. RESULTS: In S-PI, 433 subjects (STB 293; PI 140) and in S-NNRTI, 434 subjects (STB 291; NNRTI 143) were randomized and treated. Most (>85%) STB subjects had a baseline eGFR ≥90 mL/min. STB subjects with baseline eGFR <90 mL/min had smaller declines in eGFR compared to those with baseline eGFR ≥90 mL/min and similar occurrences of renal tubular laboratory abnormalities (Table 1). Rate of renal adverse events leading to study drug discontinuation were similar for the STB group (one PRT in a subject with baseline tubular laboratory abnormalities consistent with underlying PRT and one isolated increase in serum creatinine) and PI group (one isolated decrease in eGFR); none in the NNRTI group. The case of PRT improved after study drug discontinuation. There were no cases of unreported subclinical PRT in any group. CONCLUSIONS: In this virologically suppressed patient population, the renal safety of STB did not differ by baseline eGFR. The renal discontinuation rate was low in the STB group, similar to the RTV-boosted PI group, and consistent with published historical rates.
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OBJECTIVE: The objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART). METHODS: Patients aged more than 20 years who started ART during 2000-2010 (excluding IDU) in HIV clinics contributing to the UK CHIC Study were followed for mortality until 2012. We determined the latest CD4 cell count and viral load before ART and in each of years 1-5 of ART. For each duration of ART, life tables based on estimated mortality rates by sex, age, latest CD4 cell count and viral suppression (HIV-1 RNA <400âcopies/ml), were used to estimate expected age at death for ages 20-85 years. RESULTS: Of 21â388 patients who started ART, 961 (4.5%) died during 110â697 person-years. At start of ART, expected age at death [95% confidence interval (CI)] of 35-year-old men with CD4 cell count less than 200, 200-349, at least 350âcells/µl was 71 (68-73), 78 (74-82) and 77 (72-81) years, respectively, compared with 78 years for men in the general UK population. Thirty-five-year-old men who increased their CD4 cell count in the first year of ART from less than 200 to 200-349 or at least 350âcells/µl and achieved viral suppression gained 7 and 10 years, respectively. After 5 years on ART, expected age at death of 35-year-old men varied from 54 (48-61) (CD4 cell count <200âcells/µl and no viral suppression) to 80 (76-83) years (CD4 cell count ≥350âcells/µl and viral suppression). CONCLUSION: Successfully treated HIV-positive individuals have a normal life expectancy. Patients who started ART with a low CD4 cell count significantly improve their life expectancy if they have a good CD4 cell count response and undetectable viral load.
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Infecciones por VIH/mortalidad , Esperanza de Vida , Adulto , Anciano , Anciano de 80 o más Años , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1 , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Reino Unido/epidemiología , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To assess CD4 cell count recovery in people severely immunosuppressed at start of antiretroviral therapy (ART) who achieve and maintain viral load suppression. METHODS: Eligible participants from the UK Collaborative HIV Cohort Study started ART with at least three drugs after 1 January 2000. Participants were required to have pre-ART CD4 cell count below 100 cells/µl, at least 2 years of follow-up on ART, have achieved viral load suppression (≤ 50 copies/ml) by 9 months after starting ART and to have maintained this throughout follow-up. Participants were further required to be regularly engaged with care. We calculated the proportion of people who failed to achieve a CD4 cell count of more than 100, 150, 200, 350 and 500 cells/µl by the time of the last follow-up, or 5 years from start of ART, whichever occurred first (censoring date). RESULTS: Of the 400 participants [median (interquartile range) pre-ART CD4 cell count of 38 (14-65) cells/µl], 2 (0.5%), 8 (2%), 28 (7%), 131 (33%) and 259 (65%) failed to achieve a CD4 cell count of more than 100, 150, 200, 350 and 500 cells/µl, by the censoring date, respectively. Kaplan-Meier estimates of the proportion of people reaching each CD4 cell count threshold after 1 year on ART were 88, 70, 50, 14 and 3%, respectively, and after 3 years on ART, 98, 95, 90, 59 and 25%, respectively. Median (interquartile range) follow-up on ART was 3.9 (2.7-4.8) years. CONCLUSION: Given a person with pre-ART CD4 cell count below 100 cells/µl survives and maintains consistent viral load suppression on ART, there is over a 90% chance of reaching a CD4 cell count above 200 cells/µl by 3 years.
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Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Carga Viral , Adulto , Recuento de Linfocito CD4 , Femenino , Estudios de Seguimiento , Humanos , Masculino , Factores de Tiempo , Resultado del Tratamiento , Reino UnidoAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/prevención & control , Infecciones por VIH/terapia , Médicos de Familia , Síndrome de Inmunodeficiencia Adquirida/psicología , Síndrome de Inmunodeficiencia Adquirida/terapia , Actitud del Personal de Salud , Humanos , Educación del Paciente como Asunto , Relaciones Médico-Paciente , Médicos de Familia/educación , Médicos de Familia/psicologíaRESUMEN
Gynaecomastia arising in the context of antiretroviral therapy for HIV infection presents a number of challenges in diagnosis and management. We describe a thirty year old gay man with rapidly developing breast enlargement who was successfully treated with the anti-oestrogen tamoxifen.