COVID-19 and HIV viral load suppression in children andadolescents in Durban, South Africa

Background: The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions. Objectives: To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa. Method: Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends. Results: The unadjusted mean VL was 2166 (confidence interval [CI]: 252.2) and 2016 (CI: 241.9), P = 0.039, and percentage VL suppression rates (72.9%, CI: 2.4% vs 73.6%, CI: 1.8%) across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level (e.g., level 5 lockdown: ­210.5 VLs, 95% CI: ­483.0 to +62.1, P = 0.138) or excess mortality (­0.1, 95% CI: ­6.3 to 6.1, P = 0.969). A significant downward trend in VL testing over time, including during the pre-COVID-19 period (­6.6 VL per month, 95% CI: ­10.4 to ­2.7, P = 0.002), was identified. Conclusion: Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. What this study adds: Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic.

Development and validation of a simple and rapid way to generate low volume of plasma to be used in point-of-care HIV virus load technologies

ABSTRACT A new point-of-care HIV viral load, mPIMA HIV-1/2 VL, Abbott, USA, has been recently developed. This point-of-care viral load requires no skilled person to run and uses a small plasma volume (50 µL). However, obtaining 50 µL of plasma can be a challenge in limited resource settings. We validated a simple and easy method to obtain enough amount of plasma to run a point-of-care viral load. The study utilized 149 specimens from patients failing antiretroviral therapy. At least 250 µL of whole blood was collected in a microtube/EDTA from fingerstick (fs-plasma) and immediately centrifuged. Parallel collection of venous blood to obtain plasma (vp-plasma) was used to compare performance in a point-of-care viral load assay and in methodology used in centralized laboratories Abbott M2000, Abbott, USA. The procedure for plasma collection takes less than 10 min and in 94% of the cases only one fingerstick was sufficient to collect at least 250 µL of blood. The Pearson correlation coefficient value for vp-plasma versus fs-plasma ran on mPIMA was 0.990. The Bland-Altman mean difference (md) for this comparison were virtually zero (md = −0.001) with limits of agreement between −0.225 and 0.223. In addition, the Pearson correlation coefficient value for fs-plasma in mPIMA versus vp-plasma in Abbott M2000 was 0.948 for values above the mPIMA limit of quantification (LoQ; from 800 to 1,000,000 copies/mL). These results validate this simple plasma isolation method capable to be implemented in low resource countries where point-of-care decentralization is deeply needed.

Consumo de álcool de pessoas vivendo com HIV e suas implicações para os desfechos clínicos / Alcohol consumption in people living with HIV and its implications for clinical outcomes

Objetivou-se analisar a prevalência do consumo de álcool em pessoas vivendo com HIV e sua associação com os desfechos clínicos. Trata-se de um estudo transversal, analítico, realizado com pessoas que vivem com HIV em tratamento ambulatorial no município de Ribeirão Preto, SP. Realizou-se entrevista com instrumento sociodemográfico e clínico e com o Cuestionario para La Evaluación de La Adhesión al Tratamiento Antirretroviral. Para análise dos dados utilizou-se os Testes Qui-quadrado, Exato de Fisher e regressão logística, adotando p<0,05. Dos 340 participantes, a prevalência do consumo de álcool foi 40,6%, dos quais 35% apresentavam consumo leve e moderado e 5,6% alto. Identificou-se que pessoas com carga viral detectável tem 1,76 vezes mais chance (p=0,04; IC95% 1,00­3,05) de consumir álcool. O estudo evidenciou uma alta prevalência de consumo de álcool entre pessoas que vivem com HIV e o desfecho clínico que apresentou associação com o alto consumo de álcool foi a carga viral.

This study aimed to analyze the prevalence of alcohol consumption among people living with HIV and its association with clinical outcomes. It is an analytical, cross-sectional study, carried out with people living with HIV in outpatient treatment in the municipality of Ribeirão Preto, SP. An interview was carried out using a sociodemographic instrument, a clinical instrument, and the Cuestionario para La Evaluación de La Adhesión alTratamiento Antiretroviral (Assessment of Adherence to Antiretroviral Therapy Questionnaire). Chi-squared test, Fisher's Exact Test, and logistical regression, adopting p<0.05, were used for data analysis. Of the 340 participants, the prevalence of alcohol consumption was 40.6%, of whom 35% presented low to moderate consumption and 5.6% high consumption. It was identified that people with detectable viral load have 1.76 times more chance of consuming alcohol (p=0.04; 95%CI 1.00­3.05). The study showed a high prevalence of alcohol consumption among people living with HIV and the clinical outcome presenting an association with high consumption was a viral load.

Utilidad de la cuantificación de carga viral de VIH en líquido cefalorraquídeo, a propósito de un caso / Clinical utility of HIV viral load assessment in cerebral spinal fluid, a case report

Resumen La detección de virus en el líquido cefalorraquídeo (LCR) en pacientes infectados por VIH con carga viral (CV) indetectable en el plasma se ha denominado escape viral. Estas fugas pueden ser asintomáticas o asociadas con enfermedad neurológica. La discordancia de la carga viral de VIH entre plasma y LCR evidenciaría la presencia de distintos compartimentos del virus, con la posibilidad de identificar quasiespecies con mutaciones específicas que confieran resistencia a la TARV. Presentamos el caso clínico de un paciente con infección por VIH en etapa SIDA y una tuberculosis diseminada que presentó un cuadro neurológico manifestado por cefalea y un síndrome convulsivo, en que se encontró una discordancia entre la CV para VIH en plasma y LCR. El estudio genotípico del virus obtenido del LCR identificó nuevas mutaciones que determinaron un cambio de la TARV, con evolución posterior satisfactoria.

Detection of virus in cerebrospinal fluid (CSF) in HIV-infected patients with HIV viral load (VL) undetectable in plasma has been termed viral escape. These leaks may be asymptomatic from a neurological point of view, similar to plasma blips, or associated with neurological disease, with discordant VL between plasma and CSF, and may be evidence of a compartmentalization of the virus and the possibility of identifying quasispecies with mutations that confer resistance to ART. We present the case of a man with AIDS and disseminated tuberculosis who presented neurological symptomatology evidenced by headache and convulsive syndrome, who presented a discordance between plasma and CSF HIV VL; the genotypic test of the virus, obtained by lumbar puncture, identified new mutations that determined a change in ART with subsequent satisfactory evolution.

Study on liver function and viral lood of pediatric AIDS patients with HBV/HCV co-infection receiving HAART / 中国免疫学杂志

Objective:To investigate the change of liver function,viral load and CD4+T count in pediatric AIDS patients with HBV/HCV co-infection after HARRT therapy,and explore the effect of HBV/HCV co-infection on HAART.Methods:95 pediatric AIDS patients without HBV/HCV co-infection ( group A) ,9 pediatric AIDS patients with HBV co-infection ( group B) and 23 pediatric AIDS patients with HCV co-infection ( group C) who received HAART for 2 year were enrolled.Liver function,viral load and CD4+T count were detected before and after HAART.Results:After HAART for 2 years,26 patients (20.5%) were found with liver injury of grade 2 (1000.05 ) .Conclusion: Co-infection of HBV/HCV can aggravate the liver damage of HIV-1 infected children,but has no significant effect on HAART.

Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up.

The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4+ and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group) were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor). The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4+ cell count was determined using FACSCalibur flow cytometer. The WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5) at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7) for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4+ cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and the patients with high viral load had sub-therapeutic NVP plasma drug concentrations and some with undetectable d4T drug concentrations in their blood circulation.

Análisis genético del polimorfismo del virus de la inmunodeficiencia humana en pacientes colombianos / Mutational analysis of HIV in Colombian patients

Objetivo. La resistencia a los medicamentos antirretrovirales se ha asociado con mutaciones características en los genes que codifican las enzimas que son el blanco de la terapia antirretroviral. En el presente trabajo se busca evaluar, desde el punto devista cualitativo y cuantitativo, las diferentes mutaciones reveladas por la tipificación molecular de virus procedentes de diferentes pacientes remitidos al Instituto de Referencia Andino, en Bogotá, para la genotipificación con fines terapéuticos.Diseño: Se hizo la tipificación de un total de 1.064 mutaciones diferentes en virusprocedentes de 16 pacientes no relacionados entre sí, con solicitud de genotipificación del VIH para análisis de sensibilidad a antirretrovirales. Se procedió a la tabulación de las mutaciones encontradas en cuatro categorías principales: a- mutaciones asociadas a resistencia, b- mutaciones silenciosas, c- polimorfismos genéticos por fuera de los sitios asociados a resistencia, y de mutaciones en sitios de resistencia que hasta el momento no han sido asociadas a resistencia.Metodología. Se seleccionaron, en estricto orden de llegada, 16 muestras de sangre en EDTA de pacientes con solicitud de genotipificación del VIH para análisis de sensibilidad a antirretrovirales. Se extrajo el ARN viral de cada muestra por el métodoQIAamp® y se procedió a su amplificación por medio de la PCR con transcriptasa inversa (RT-PCR). Una vez amplificado el ácido nucleico viral, se procedió a su tipificación molecular en el secuenciador LongReadTower-Opengene®, utilizando el estuche Trugene HIV-1®. Las secuencias obtenidas se transcribieron a hoja electrónica Excel®, y se hizo un cálculo de frecuencias de mutaciones por conteo directo...

Objective: Resistance to antiretroviral drugs has been associated with characteristic mutations in the genes that encode enzymes which are the target of anti-retroviral therapy. In this paper we evaluate the different mutations revealed by molecular typing of viruses from differentpatients who were referred to be genotyped at the Instituto de Referencia Andino in Bogotá fortherapeutic purposes. Design: A total number of 1064 mutations in viruses from 16 HIV infected unrelated patientswere initially genotyped for the analysis of sensitivity to antiretrovirals. Afterwards, weproceeded to the tabulation of the mutations found in four main categories: a- resistance mutations, b- silent mutations, c-genetic polymorphisms outside of sites associated with resistance, and d- mutations at sites not yet associatedwith resistance. Materials and methods: Sixteen EDTA blood samples drawn from patients with HIV genotyping application for analysis of sensitivity to antiretroviral drugs were selected in strict order of arrival. Viral RNA was extracted from each sample by the QIAamp® method, and we then proceeded to its amplification by reverse transcriptase PCR (RT-PCR). Once the viral nucleic acid was successfully amplified, we proceededto molecular typing in the sequencer LongRead-Tower-Opengene®, using the Trugene® HIV-1 kit. The sequences obtained were transcribed toan Excel® spreadsheet, to calculate the frequencies of mutations by direct counting...

Avaliação da excreção genital do HIV-1 em mulheres menopausadas e em idade fértil: prevalência e fatores associados / HIV cervicovaginal shedding among postmenopausal and fertile-aged women: prevalence and associated factors

INTRODUÇÃO: Poucos estudos têm focado as modificações fisiológicas que ocorrem no trato genital de mulheres menopausadas infectadas pelo HIV e sua associação com a excreção genital do vírus. Nesse estudo de corte transversal, comparou-se a excreção genital do HIV em mulheres menopausadas e em idade fértil em acompanhamento em um centro especializado em São Paulo, Brasil. Investigou-se também a associação entre a excreção genital de RNA de HIV e a viremia em ambos os grupos. Fatores associados com a intensidade da excreção genital de HIV também foram pesquisados, incluindo achados ginecológicos e marcadores de progressão da infecção por HIV. MÉTODOS: 146 mulheres infectadas pelo HIV [73 menopausadas (M)/73 em idade fértil (F)] foram selecionadas em Serviço de Extensão ao Atendimento de Pacientes com HIV/Aids Casa da Aids do Hospital das Clínicas da FMUSP, São Paulo, Brasil. As mulheres menopausadas referiram tempo médio de 8,17 anos (DP=6 anos) de menopausa. A contagem de linfócitos T CD4+ foi obtida por citometria de fluxo e a quantificação do RNA do HIV no plasma e no lavado cervicovaginal (LCV) foi realizada por RT-PCR quantitativo, utilizando-se o kit Cobas Amplicor HIV-1 Monitor Test®, no método ultrasensível. Cloreto de lítio foi introduzido no tampão para obtenção do LCV e quantificado antes e depois da coleta do lavado, a fim de determinar o fator de diluição de cada amostra. A deteção do gene SRY por PCR também foi realizada a fim de eliminar amostras com eventual contaminação espermática. A prevalência de excreção genital foi estimada para ambos os grupos e os fatores associados à intensidade da excreção viral foram investigados, utilizando-se modelo de regressão linear múltipla. As variáveis com p<0,2 na análise bivariada foram incluídas na análise multivariada, assim como o grupo em estudo (M ou F). O modelo final incluiu fatores que se mostraram independentemente associados com a intensidade da excreção genital de HIV...

BACKGROUND: Few studies have focused on physiological modifications that occur in the genital tract of HIV-infected postmenopausal women and their association with HIV cervicovaginal shedding. In this cross-sectional study we evaluated and compared HIV genital shedding among postmenopausal and fertile-aged women under care at a specialized center in Sao Paulo, Brazil, investigating the association between HIV-RNA shedding and HIV plasma viral loads in both groups. Factors associated with higher HIV shedding were also investigated, including gynaecological features and HIV disease progression markers. METHODS: 146 women living with HIV [73 postmenopausal (PM)/73 in fertile-aged (F)] were enrolled at the HIV Clinic, University of São Paulo Medical School, Brazil. Postmenopausal women referred a mean duration of 8.17y (SD=6y) since menopause. CD4+ cell counts were obtained by flow cytometry and HIV-RNA was quantified in plasma and in cervicovaginal lavages (CVL) by RT-PCR, using Cobas Amplicor HIV-1 Monitor Ultrasensitive Test. Lithium chloride was introduced into the CVL buffer and measured before and after CVL collection in order to determine the dilution factor for each specimen. SRY gene detection by PCR was also performed in all samples in order to rule out sperm contamination. Prevalence of HIV genital shedding was estimated for both groups and factors associated with the intensity of viral shedding were investigated, using a multiple linear regression model. Variables with p<0.2 in bivariate analysis were included in multivariate analysis, as well as the study group (PM and F). The final model included factors shown to be independently associated with intensity of HIV genital shedding. RESULTS: The prevalence of HIV-RNA genital shedding was similar in both groups. (PM: 17.8%, 95%CI 9.8 28.5; F: 22%, 95%CI 13.1 33.1, p=0.678). Likewise, the intensity of HIV shedding was shown not to differ between PM and F women...

Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long-Term antiretroviral therapy, and with absent-negligible immunodeficiency

A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/µL. After treatment with a highly active antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his CD4+ lymphocyte count was 930 and 439 cells/µL, respectively, and a viral load slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but a presentation with a concurrent CD4+ count above 1,000 cells/µL remains a rare exception, as well as the two isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/µL, and a residual HIV viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIV-infected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities.

La carga viral y células TCD4+ en pacientes infectados con el virus de inmunodeficiencia humana (VIH) coinfectados con sífilis / The viral load and TCD4+ cells in human immunodeficiency virus (HIV) infected patients coinfected with syphilis

La coinfección con sífilis en el paciente infectado con VIH-1 ha aumentado en los últimos años. La sífilis se ha asociado con activación inmunológica, pero el efecto de la misma sobre los parámetros inmunovirológicos en esta población aún son controversiales. El objetivo es evaluar el efecto de la sífilis en el contaje de células TCD4+ y la carga viral del paciente VIH+. Se realizó un estudio retrospectivo, multicéntrico, de casos y controles, extrayendo de las historias clínicas de los pacientes VIH+ que asistieron a control en los últimos 10 años, los reportes de contaje de células TCD4+ y carga viral, antes, durante y después del diagnóstico de sífilis para compararlos entre sí y con un grupo control. 48 pacientes VIH+ diagnosticados con sífilis conformaron el grupo de estudio y 56 sin sífilis, el grupo control. 14 (29%) pacientes con sífilis secundaria, 33 (69%) latente y 1 (2%) primaria. 38 (80%) recibían TARV en el momento de la sífilis. 24 (70%) elevaron sus valores de TCD4+ durante la enfermedad y 27(59%) posterior a ella, con una media de elevación de 19,41 celulas x mm³ (p=0,43) y 23,74 células x mm³ (p=0,28) respectivamente. Las determinaciones de carga viral se elevaron durante la enfermedad en 8 (38%) pacientes con una media de elevación de 64688 copias ARN-VIH/ml (4,96 log10) (p=0,03), y disminuyeron en 13 (45%) con una media de -1163 copias de ARN/ml (3,06 log10) (p=0,99) posteriormente. La sífilis en el paciente VIH+ estuvo asociada a elevaciones significativas en la carga viral y a cambios no significativos en el contaje de células TCD4+ durante la enfermedad.

Syphilis co-infection in HIV-1 patients has increased in recent years. Syphilis has been linked to immunoactivation, however, its effect on immunovirological parameters in this population is still controversial. Objective evaluate the effect of syphilis on the TCD4+ cell count andviral load of the HIV+ patient. A retrospective, multicenter case-control study was conducted by extracting the TCD4+ cell counts and viral load before, during, and after diagnosis of syphilis, from the clinical records of HIV+ patients who attended check-ups in the past 10 years, in order to compare them among themselves and against a control group. Seroprevalence of HIV/Syphilis co-infection was 18%. 48 HIV+ patients diagnosed with syphilis formed the study group, while 56, without syphilis, the control group. 14 (29%) had secondary, 33 (69%) latent and 1 (2%) primary syphilis. 38 (80%) received ART at the time of their syphilis. Of 24 (70%) the TCD4+ values increased during illness, and of 27 (59%) they increased subsequently, with a mean increase of 19.41 cell/mm³ (p=0.43) and 23.74 cell/mm³ (p=0.28) respectively. Measurements of the viral load increased in 8 (38%) patients during the disease with a mean increase of 64,688 HIV RNA copies/ml (4.96 log10) (p=0.03); and in 13 they decreased subsequently (45%) with a mean of -1,163 RNA copies/ml (3.06 log10) (p=0.99). Syphilis in the HIV+ patient was linked to significant increases in the viral load and to non-significant changes in the TCD4+ cell count during the disease.