Do people living with HIV face more secondary cancers than general population: From the French CANCERVIH network.

INTRODUCTION: People living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase. METHODS: We reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH national multidisciplinary board since 2014. We included all cases with a history of cancer, and studied the incidence and types of second cancers. RESULTS: In total, 719 cases were reviewed, out of which 94 (13%) had a history of at least one cancer. For the first primary cancers, 46 (49%) were AIDS-defining cancers (ADCs) and 48 (51%) were non-AIDS-defining cancers (NADCs). Kaposi sarcoma (33%) and NHL (15%) occurred most frequently as first cancers. Among the first cancers that were ADCs, 15% of the second cancers were NHL, 11% anal canal cancers, 9% bladder and 9% Hodgkin lymphomas. Among the first cancers that were NADCs, 38% of the second cancers were lung cancers, 8% bladder, 8% head and neck and 8% NHL. DISCUSSION: With the aging of PLWHIV, the incidence of second and subsequent cancers is expected to increase in this population. Immuno-virological control should be maintained. Increased surveillance, early prevention and screening programs should be offered to all PLWHIV, including those with an undetectable HIV viral load and/or immune restoration.

Impact of the COVID-19 pandemic situation on HIV care in Liège, Belgium.

BACKGROUND: Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult. OBJECTIVE: Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). METHODS: Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020. RESULTS: Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4 + T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia. CONCLUSIONS: Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients.

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

Aging with HIV: a practical review

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged >50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged >50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged >50 years focusing on practical features related to the clinical approach and long-term follow-up of this population.

Considerations for the long-term management of women living with HIV in Europe.

The average age at which women are first diagnosed with HIV is increasing and, due to advances in antiretroviral therapy (ART), women are living with HIV for longer. Once regarded as a fatal disease of young males, HIV is now considered a lifelong chronic condition affecting both men and women into older age. This raises questions for the long-term management of women living with HIV in Europe, such as how age affects the ART response, what the consequences are of long-term ART, and whether the comorbidities of ageing and menopause are different in women with HIV compared with men or uninfected women. Non-AIDS-related events, such as cancer, are increasingly responsible for the deaths of women with HIV, and European guidelines now recommend that they undergo regular screening for breast, cervical and colorectal cancer, and vaccination for human papillomavirus. The other major outcome of the greater life expectancy of women living with HIV is that a greater number are reaching menopause. Some studies suggest that HIV infection is linked with earlier onset of menopause and altered menopausal symptomatology. Many questions remain, and there is a need for more studies addressing ageing and sustained ART use in women living with HIV in Europe.

Una década de terapia anti-retroviral: Perfil de pacientes con 10 años de triterapia de alta efectividad / A decade of antiretroviral therapy: a profile of patients with 10 years of highly effective triple therapy

Introduction: Highly effective antiretroviral triple therapy (TAR3) has led to a significant increase in survival of patients (pts) infected with human immunodeficiency virus. In 1999 it was started in the Chilean public health system, including Arriarán Foundation (FA) access to TAR, reaching full coverage since 2003. By October 31, 2009 124 pts had reached 10 years of uninterrupted TAR3 in FA. Objective: To describe and analyze the profile of pts, their therapeutic regimen (s) and clinical outcomes during 10 years of TAR3. Methods: Retrospective descriptive study. We reviewed the records of pts who had reached 10 years of uninterrupted TAR3 in FA. Demographic data, baseline and virological staging at start of TAR3, comorbidities and complications were recorded. Drug regimens used were analyzed, as well as toxicity, virological and immunological outcomes, frequency and reasons for change in therapy. Complications were classified as opportunistic and not opportunistic during this evolution and the latest known clinical and laboratory data were registered. A database program based on Excel was used. Results: 121/124 pts were available for analysis, 76.8% male, male-female ratio was 3.3:1. Baseline median age: 36 years (20-69); CD4 cells 176/ mm³ (8-1,224) with 65.3% < 200; median viral load (STL): 60,078 copies/ml (1,100- 7,900,000); 36.3% were in clinical AIDS stage. Patients received an average of 3.5 therapies regimens during the decade (range, 1 [14 pts, 11.5%] to 7 [3 pts, 2.4%]), with average duration of 42 months each and a median of 36 months. As initial TAR3 regimen 2 backbone nucleoside analogues (ITRN) was the most frequent, with a protease inhibitor (PI) in 51.2% and non-nucleoside RTIs (NNRTIs) in 38.8%. Adverse reactions were the main reason for change of therapy (24.7%), followed by virological failure (24.2%) and treatment simplification (16.6%). At the latest assessment, all with > 10 years of TAR3 median CD4 was 602 cells/mm³, 11 pts (9%) had CD4 < 200/mm³; 85.2% had undetectable VL (< 80 copies/mL); the remaining 14.8% had a median of 1,800 copies/mL. Only 2 pts (1.7%) were in AIDS clinical stage. Current regimens were 2 NRTI plus 1 NNRTI in 61 pts (50.4%), 2 or more NRTI plus 1 PI in 46 (38%). Seventy two pts (60.3%) had chronic comorbidities at latest follow up. Dyslipidemia, hypertension, diabetes mellitus and renal failure were the most frequent conditions; 17 pts (14%) had clinical lipodystrophy secondary to TAR. Conclusion: Achieving a decade of TAR is already a reality and in the short term will be routine. This is rarely achieved with the initial therapeutic regimen. The major obstacles to prolonged maintenance of a single therapeutic regimen have been adverse effects and virological failure, although current drugs with better efficacy and safety profile may allow longer use for each regimen. Despite the difficulty of treating these pts, they can achieve long-term survival with good virologic control, immune recovery and absence of opportunistic complications associated with HIV infection. Nonetheless, the high frequency of non opportunistic chronic comorbidities and antiretroviral therapy side effects after prolonged or life-long use is becoming a major issue.

La introducción de la triterapia anti-retroviral de alta efectividad (TAR3) ha llevado a un significativo aumento en la sobrevida de los pacientes infectados por virus de inmunodeficiencia humana. En 1999 se inició en el sistema público de salud chileno, incluida la Fundación Arriarán (FA) el acceso progresivo a TAR3, que alcanzó cobertura completa desde 2003. En FA al 31 de octubre de 2009 se compatibilizaban 124 pacientes (pts) que habían alcanzado 10 años de TAR3 ininterrumpida. Objetivo: Describir y analizar el perfil de los pts, sus terapias y la evolución clínica durante el período de 10 años de TAR3. Material y Método: estudio descriptivo y retrospectivo. Se revisaron las fichas de los pts que alcanzaron 10 años de TAR3 en FA. Se registraron datos demográficos, clínicos y clasificación por etapas, co-morbilidades y complicaciones al inicio de tratamiento. Se analizaron los esquemas terapéuticos recibidos, toxicidades y desenlaces virológicos e inmunológicos, así como la frecuencia y razones de cambio de terapias, las complicaciones oportunistas y no oportunistas durante esta evolución y el último estado clínico y de laboratorio conocido. Se empleó una base de datos en base al programa Excel. Resultados: se lograron analizar 121/124 pts, 76,8% hombres, relación hombre:mujer 3,3:1. Mediana basal: edad, 36 años (20-69); recuento de linfocitos CD4 de 176 céls/mm³ (8-1.224), con 65,3% < de 200 céls/mm³; carga viral (CV): 60.078 copias/ml (1.100 -7.900.000); 44/121 (36,3%) en etapa SIDA clínica inicial. Los pacientes recibieron un promedio de 3,5 esquemas de terapias durante el decenio (rango, 1 [14 pts, 11,5 %] a 7 [3 pts, 2,4 %]), con duración promedio de 42 meses en cada uno y una mediana de 36. TAR3 inicial con dos análogos nucleosídicos (ITRN) fue lo más frecuente, con un inhibidor de la proteasa (IP) en 51,2% o con ITR no nucleosídico (ITRnN) en 38,8%. Las reacciones adversas fueron el principal motivo de cambio de esquemas (24,7%), seguido de fracaso virológico (24,2%) y simplificación terapéutica (16,6%). En su última evaluación y con > 10 años de TAR3 la mediana de linfocitos CD4 era de 602 céls/mm³; había 11 pts (9 %) con CD4 < 200/ mm³; 85,2% estaba con CV indetectable (< 80 copias/ mL), 14 (14,8%) con detectabilidad viral, y éstos con una mediana de 1.800 copias/mL. Sólo 2 pts (1,7%) estaban en etapa clínica de SIDA. El esquema de TAR3 actual más frecuente era de dos ITRN más un ITRnN, en 61 pts (50,4%) y luego dos ITRN más un IP en 46 (38%). En 72 pts (60,3%) se pesquisaron co-morbilidades crónicas: dislipidemias, hipertensión arterial, diabetes mellitus y/o insuficiencia renal; 17 pts (14%) presentaban lipodistrofia clínica secundaria a TAR3 Conclusión: Alcanzar una década de TAR3 ya está siendo una realidad y a corto plazo será rutinario. Esto rara vez se logra con la primera terapia, aunque esquemas contemporáneos más efectivos y seguros pueden hacerlo posible a futuro. Los principales obstáculos para lograr mantención prolongada de un solo esquema terapéutico son los efectos adversos y el fracaso virológico. A pesar de las dificultades terapéuticas estos pts pueden alcanzar sobrevida a largo plazo con buen control virológico, recuperación inmune y control de las complicaciones oportunistas asociadas a la infección por VIH. Destaca la alta frecuente de co-morbilidades crónicas no oportunistas y secuelas de la terapia anti-retroviral.

Oral squamous cell carcinoma in human immunodeficiency virus positive patients: clinicopathological audit.

BACKGROUND: Most human immunodeficiency virus positive patients now have a longer life expectancy, with the advent of highly active antiretroviral therapy. However, they are now at increased risk of developing a malignancy during their lives. AIM: To investigate the age at which oral squamous cell carcinoma presents in patients infected with human immunodeficiency virus. STUDY DESIGN: Prospective, clinicohistopathological audit of patients infected with human immunodeficiency virus. RESULTS: Of 200 human immunodeficiency virus positive patients, 16 (8 per cent) presented with oral squamous cell carcinoma (nine women and seven men; age range 18-43 years, mean age 31.7 years). The majority of patients (62.5 per cent) had stage III and IV disease (tumour-node-metastasis staging). There was a predilection for poorly differentiated oral squamous cell carcinoma (using Broder's histopathological classification). CONCLUSION: Oral squamous cell carcinoma associated with human immunodeficiency virus infection appears to present at a relatively young age.

Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study.

Durable control of human immunodeficiency virus (HIV) replication and lack of disease progression in the absence of antiretroviral therapy were studied in a military cohort of 4586 subjects. We examined groups of elite controllers (ie, subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% [95% confidence interval {CI}, 0.35%-0.80%]), viremic controllers (ie, subjects with plasma HIV RNA levels of 50-2000 copies/mL; prevalence, 3.34% [95% CI, 2.83%-3.91%]), and subjects with a lack of disease progression (ie, long-term nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32% [95% CI, 2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95% CI, 1.52%-2.68%]). For elite and viremic controllers, spontaneous virologic control was established early and was typically observed when the initial viral load measurement was obtained within 1 year of estimated seroconversion. Elite controllers had favorable time to development of AIDS (P=.048), a CD4 cell count of 350 cells/microL (P= .009), and more-stable CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer survival time (P=.001), even after adjustment for differing periods of invulnerability (P= .042). Definitions of controllers and LTNPs describe distinct populations whose differing clinical outcomes improve with the stringency of criteria, underscoring the need for comparability between study populations.

Neonatal factors associated with HIV long term non-progressors in a cohort of vertically infected children in Rio de Janeiro, Brazil ("Peixe" Project)

There are only scarce data on HIV progression in vertically infected children in developing countries. The aim of this study is to describe factors from neonatal period associated with long term non-progression (LTNP), in a Brazilian cohort. A cohort study, with data systematically collected from the "Peixe" Cohort (cohort study of children conducted at the main HIV Pediatric Center in Rio de Janeiro, from 1996 to 2005). The study included children who were vertically infected and started follow up at 5 years of age or younger. LTNP, defined as not reaching category C or severe immunosuppression before 5 years of age. Neonatal and demographic factors were studied. Variables with p-value<0.15 were included in a logistic regression model. 213 patients were included, of whom 42 percent (89/213) were classified as LTNP. Variables independently associated with LTNP were: baseline (at study entry) CD4+ cells (per percent) (OR= 1.06, 95 percentCI=1.01-1.12); age of initiating follow-up, per month (OR= 1.03, 95 percentCI=1.01-1.06); ZDV use duriing newborn period (OR= 3.31, 95 percentCI=0.86-12.71); use of antiretroviral (ART) before classification C or severe immunosuppression (OR= 5.89, 95 percentCI=2.03-17.10). Adjusting for age at the beginning of follow-up, antiretroviral that was unsuccessfully used to prevent maternal-to-child transmission (ZDV use in neonatal period) was associated with better prognosis. ARTs initiation before category C or severe immunosuppression was also associated with LTNP.

Impacto de la infección por el virus de la inmunodeficiencia humana Tipo-1 en la población hemofílica / The impact of human immunodeficiency virus infection in haemophilic patients

En los últimos 3 años se han producido notables avances en el tratamiento de la enfermedad HIV/SIDA. En este trabajo se compara la evolución y respuesta al tratamiento con antirretrovirales en 175 pacientes hemofílicos HIV (+) evaluados entre los años 1983 y 1995 con 54 pacientes de las mismas características, pero que recibieron terapias combinadas de alta eficacia, entre los años 1996 y 1999. Se evaluaron los siguientes parámetros: influencia de la edad al momento de la infección con el tiempo de sobrevida libre de enfermedad, incidencia de complicaciones oportunistas, tipo y severidad de la hemofilia en relación con el riesgo de infección por el retrovirus, respuesta al tratamiento antirretroviral, efectos adversos relacionadas con el mismo y modificaciones acaecidas en los niveles de linfocitos T CD4 (+) y en los valores de la carga viral en plasma.