Performance of a Novel Low-Cost, Instrument-Free Plasma Separation Device for HIV Viral Load Quantification and Determination of Treatment Failure in People Living with HIV in Malaysia: a Diagnostic Accuracy Study

ABSTRACT HIV viral load (VL) testing is the recommended method for monitoring the response of people living with HIV and receiving antiretroviral therapy (ART). The availability of standard plasma VL testing in low- and middle-income countries (LMICs), and access to this testing, are limited by the need to use fresh plasma. Good specimen collection methods for HIV VL testing that are applicable to resource-constrained settings are needed. We assessed the diagnostic performance of the filtered dried plasma spot (FDPS), created using the newly developed, instrument-free VLPlasma device, in identifying treatment failure at a VL threshold of 1,000 copies/ml in fresh plasma. Performance was compared with that of the conventional dried blood spot (DBS). Venous blood samples from 201 people living with HIV and attending an infectious disease clinic in Malaysia were collected, and HIV VL was quantified using fresh plasma (the reference standard), FDPS, and DBS specimens. VL testing was done using the Roche Cobas AmpliPrep/Cobas TaqMan v2.0 assay. At a threshold of 1,000 copies/ml, the diagnostic performance of the FDPS was superior (sensitivity, 100% [95% confidence interval {CI}, 89.1 to 100%]; specificity, 100% [95% CI, 97.8 to 100%]) to that of the DBS (sensitivity, 100% [95% CI, 89.4 to 100%]; specificity, 36.8% [95% CI, 29.4 to 44.7%]) (P < 0.001). A stronger correlation was observed between the FDPS VL and the plasma VL (r = 0.94; P < 0.001) than between the DBS VL and the plasma VL (r = 0.85; P < 0.001). The mean difference in VL measures between the FDPS and plasma (plasma VL minus FDPS VL) was 0.127 log10 copies/ml (standard deviation [SD], 0.32), in contrast to –0.95 log10 copies/ml (SD, 0.84) between the DBS and plasma. HIV VL measurement using the FDPS outperformed that with the DBS in identifying treatment failure at a threshold of 1,000 copies/ml and compared well with the quantification of VL in plasma. The FDPS can be an attractive alternative to fresh plasma for improving access to HIV VL monitoring among people living with HIV on ART in LMICs.

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Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

AIDS Research and Therapy ◽

10.1186/s12981-021-00336-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Anita Mesic ◽

Alexander Spina ◽

Htay Thet Mar ◽

Phone Thit ◽

Tom Decroo ◽

...

Keyword(s):

Viral Load ◽

Virological Failure ◽

Antiretroviral Treatment ◽

People Living With Hiv ◽

First Line ◽

Hiv Viral Load ◽

Loss To Follow Up ◽

History Of ◽

Living With Hiv

Abstract Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

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Cocaine Use, Oxidative Stress and Inflammation Among People Living with HIV in the MASH Cohort in Miami (P19-002-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.p19-002-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Alhanoof Alohaly ◽

Adriana Campa ◽

Leslie Seminario ◽

Marianna Baum

Keyword(s):

Oxidative Stress ◽

Viral Load ◽

Inflammatory Diseases ◽

Antioxidant Defense System ◽

People Living With Hiv ◽

Oxidized Glutathione ◽

Hiv Viral Load ◽

Cross Sectional ◽

Cocaine Use ◽

Living With Hiv

Abstract Objectives HIV infection and cocaine use contribute to oxidative stress; persistent oxidative stress leads to rapid rates of glutathione (GSH) consumption. GSH is an abundant intracellular antioxidant and is synthesized from its precursor amino acids. HIV promotes changes in the components of the antioxidant defense system, resulting in GSH depletion and may cause DNA damage, and is associated with chronic inflammatory diseases. Therefore, the aim is to assess oxidative stress, and biomarkers of inflammation in HIV-infected individuals from the Miami Adult Studies on HIV (MASH) cohort, on stable antiretroviral therapy (ART), with controlled HIV viral load. Methods A cross-sectional study of participants in the MASH cohort in Miami. Participants were consented and blood was collected for C-reactive protein (CRP), oxidized glutathione and % of reduced to oxidized glutathione (GSH: GSSG). Anthropometrics included body fat measured by the bioimpedance analysis machine. Results Mean age was 54.6 ± 6.3 years, 67% were male, and 50% used cocaine, mean BMI was 26.2 ± 3.1, CRP was 7.1 ± 12.4, oxidized glutathione was 34.4 ± 32.4 mmol, and the ratio of GSH: GSSG 4.86 ± 4.7. All participants had undetected viral load and were mainly overweight (70%) with a mean fat% of 28.0 ± 7.1. Cocaine use was strongly related with CRP (r = 401, P = 0.014) and GSH: GSSG (r = −389, P = 0.017) ; BMI was lower with age (r = −0.502, P = 0.024); and fat contain was lower in males (r = −0.474, P = 0.004); males also had significantly higher oxidized glutathione (r = 0.384, P = 0.018); age was inversely correlated with BMI (r = −0.335, P = 0.027). A nutritional supplementation with antioxidants with a longitudinal follow-up of outcomes is in progress. Conclusions Our findings suggest that cocaine use is significantly associated with markers of inflammations and oxidative stress in people living with HIV who are already at risk for these conditions, and interventions with antioxidants and detoxification interventions are important for these participants. Funding Sources National Institute on Drug Abuse.

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Daily and near-daily cannabis use is associated with HIV viral load suppression in people living with HIV who use cocaine

AIDS Care ◽

10.1080/09540121.2020.1799922 ◽

2020 ◽

pp. 1-8

Author(s):

Deepika E. Slawek ◽

Julia Arnsten ◽

Nancy Sohler ◽

Chenshu Zhang ◽

Robert Grossberg ◽

...

Keyword(s):

Viral Load ◽

Cannabis Use ◽

People Living With Hiv ◽

Viral Load Suppression ◽

Hiv Viral Load ◽

Living With Hiv

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Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV

PLoS ONE ◽

10.1371/journal.pone.0255834 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255834

Author(s):

Bogusz Jan Aksak-Wąs ◽

Miłosz Parczewski ◽

Anna Urbańska ◽

Małgorzata Hackiewicz ◽

Justyna D. Kowalska

Keyword(s):

Viral Load ◽

Cd4 Count ◽

Baseline Viral Load ◽

People Living With Hiv ◽

Hiv Viral Load ◽

Cross Sectional ◽

End Point ◽

Lower Baseline ◽

Route Of Transmission ◽

Living With Hiv

Background The life expectancy of people living with HIV (PLWH) remains shorter than that of the general population, despite significant improvement in the recent years. Mortality in HIV-infected individuals may be associated with a higher viral load at of diagnosis, a lower CD4 count, or clinical variables such as sex or route of transmission. This article investigated the role of the HLA-B*5701 varian on mortality among PLWH. Methods Material for the analysis consist of the data of 2,393 patients for whom the HLA-B*57 variant was known. Those patients were followed under the care of the Infectious Diseases Hospital in Warsaw (n = 1555) and the Clinic of Acquired Immunodeficiency of the Pomeranian Medical University in Szczecin (n = 838). Factors such as age, gender, date of HIV diagnosis, route of transmission, date of death, baseline HIV viral load and baseline CD4 counts, were collected, and end-point cross-sectional analyses were marked at 60, 120, 180 and 240 month of observation. Results HLA-B*5701 allele was found in 133 (5.5%) analyzed cases. Median age was notably higher for HLA-B*5701 positive patients [32.7 (28.3–41.3) vs. 31.6 (26.8–38.3)years p = 0.02]. HLA-B*5701 was associated with lower baseline viral load [4.21 (3.5–4.8) vs. 4.79 (4.2–5.3)log copies/ml p<0.001] and higher CD4count [448 (294.5–662) vs. 352 (176–514) cells/μl p<0.001]. There were no association between HLA-B*5701 and survival for any given end-point. Higher mortality was associated to male gender, intravenous drug users, lower CD4 count at baseline and higher baseline viral load. Conclusions In our study, the presence of HLA-B*5701 allel was not associated with mortality rate of HIV infected patients, irrespective of being associated with both higher baseline CD4 + cell count and lower baseline HIV viral load.

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Risk of adverse COVID-19 outcomes for people living with HIV: a rapid review and meta-analysis

10.1101/2020.09.22.20199661 ◽

2020 ◽

Author(s):

Maya Mellor ◽

Anne Bast ◽

Nicholas Jones ◽

Nia Roberts ◽

Jose Ordonez-Mena ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Meta Analysis ◽

Cd4 T Cell ◽

Rapid Review ◽

People Living With Hiv ◽

Hiv Viral Load ◽

Increased Risk ◽

Living With Hiv ◽

Cd4 T Cell Count

Objective: To assess whether people living with HIV (PLWH) are at increased risk of COVID-19 mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk. Design: Rapid review with meta-analysis and narrative synthesis. Methods: We searched databases including Embase, Medline, medRxiv, and Google Scholar up to 26th August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies. Results: We identified 1,908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality (hazard ratio (HR) 1.93, 95% Confidence Interval (CI): 1.59-2.34) compared to people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalised cohorts (HR 1.54, 95% CI: 1.05-2.24) and studies of PLWH across all settings (HR 2.08, 95%CI: 1.69-2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower-quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir-disoproxil-fumarate (TDF)-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by comorbidities. Conclusion: Evidence is emerging that suggests a moderately increased risk of COVID-19 mortality amongst PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T cell count, HIV viral load, ART and the use of TDF is warranted.

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Increased Prevalence of Liver Fibrosis and HIV Viremia among Patients with HIV, HBV, and Tuberculosis in Botswana

Pathogens ◽

10.3390/pathogens9110950 ◽

2020 ◽

Vol 9 (11) ◽

pp. 950

Author(s):

Bonolo B. Phinius ◽

Motswedi Anderson ◽

Lynnette Bhebhe ◽

Kabo Baruti ◽

Godiraone Manowe ◽

...

Keyword(s):

Viral Load ◽

Liver Fibrosis ◽

People Living With Hiv ◽

Hiv Viral Load ◽

Art Initiation ◽

Increased Risk ◽

Significant Difference ◽

B Virus ◽

Apri Score ◽

Living With Hiv

People with concomitant human immunodeficiency virus (HIV) and tuberculosis (TB) have an increased risk of hepatotoxic reactions due to antiretroviral therapy (ART) and anti-TB therapy (ATT). Concomitant hepatitis B virus (HBV) in these patients may lead to poorer health outcomes. To assess liver enzyme levels and immune response in adults with HIV, HBV, and TB, data from 300 antiretroviral-naïve people living with HIV (PLWHIV) were analyzed. The prevalence of HIV/HBV (cHIV/HBV) and HIV/TB (cHIV/TB) was 28% (95% CI: 23.0–33.4) and 10% (95% CI: 6.8–14.0), respectively. HIV/HBV/TB (cHIV/HBV/TB) prevalence was 5.3% (95% CI: 3.1–8.5). There was a statistically significant difference between the groups of participants in HIV viral load (p = 0.004), hemoglobin levels (p = 0.025), and body mass index (p = 0.011). A larger proportion of cHIV/HBV/TB participants (37.5%) had an aspartate aminotransferase to platelet ratio index (APRI) score ≥0.5 (p = 0.013), a lower cutoff for significant liver fibrosis. Immunological non-responders (CD4+ T-cell count <20% gain and HIV viral load <400 copies/mL at 6 months) were observed in all groups except those with cHIV/TB. Our findings support the need to screen for infections that could cause excessive liver damage prior to ATT or ART initiation, such as HBV.

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HIV Infection and the Risk of World Health Organization–Defined Sudden Cardiac Death

Journal of the American Heart Association ◽

10.1161/jaha.121.021268 ◽

2021 ◽

Vol 10 (18) ◽

Author(s):

Matthew S. Freiberg ◽

Meredith S. Duncan ◽

Charles Alcorn ◽

Chung‐Chou H. Chang ◽

Suman Kundu ◽

...

Keyword(s):

Viral Load ◽

Hiv Infection ◽

World Health ◽

People Living With Hiv ◽

Hiv Viral Load ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Health Organization ◽

Living With Hiv ◽

Cd4 Cell

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)–defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow‐up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04–1.25), adjusting for possible confounders. In analyses with time‐varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm 3 (HR, 1.57; 95% CI, 1.28–1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46–1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm 3 (HR, 1.03; 95% CI, 0.90–1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87–1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO‐defined SCD among those with elevated HIV viral load or low CD4 cell counts.

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The Prevalence of HIV Load Suppression and Related Factors Among Patients on ART at Phedisong 4 Clinic, Pretoria, South Africa

The Open Public Health Journal ◽

10.2174/1874944501811010135 ◽

2018 ◽

Vol 11 (1) ◽

pp. 135-146

Author(s):

N.J. Mogosetsi ◽

L.H. Mabuza ◽

G.A. Ogunbanjo

Keyword(s):

Viral Load ◽

Clinical Characteristics ◽

People Living With Hiv ◽

Large Sample Size ◽

Viral Load Suppression ◽

Hiv Viral Load ◽

Related Factors ◽

Behavioural Characteristics ◽

Patient Groups ◽

Living With Hiv

Background: Globally, the benefits of viral load suppression in improving the lives of people living with HIV/AIDS have been established. In 2010, the South African Government decentralised ART to the primary care level. This study intended to determine the effect of this decentralisation in achieving viral load suppression among patients. Objective: To determine the prevalence of HIV viral load suppression and factors related to the suppression among patients initiated on ART at Pedisong 4 clinic, Tshwane District in Pretoria. Methods: A prospective cohort study was conducted on 98 patients initiated on ART between 01 November 2012 and 30 April 2013. Based on the viral load results, they were divided into those who achieved Viral Load Suppression (VLS), and those who did not (NVLS). Analyses were done using SAS® (version 9.2) for Microsoft software. A p < 0.05 was considered significant. Results: Ninety patients (91.8%; 95%CI, 84.7% – 95.8%) achieved viral load suppression while eight (8.2%; 95%CI, 4.2% – 15.3%), did not. Of the 98 patients, 63 (64%) were female. In the NVLS group, the female to male ratio was 7:1 (p = 0.038). There was no relationship between viral load suppression and patients’ baseline characteristics, behavioural characteristics and clinical characteristics (p > 0.05). ART adherence reported in both patient groups was ≥ 87.0%. Conclusion: There was good viral load suppression in patients initiated on ART at Pedisong 4 clinic. Patients’ baseline, behavioural and clinical characteristics were not related to viral load suppression, necessitating further large sample size studies in various health facilities.

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923. Long-term Mortality after Histoplasma Infection in People Living with HIV

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1110 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S495-S496

Author(s):

Joseph Cherabie ◽

Lindsey Larson ◽

Sasinuch Rutjanawech ◽

Alexander Franklin ◽

Michael J Hendrix ◽

...

Keyword(s):

Viral Load ◽

Clinical Characteristics ◽

Modern Art ◽

Early Mortality ◽

People Living With Hiv ◽

Hiv Viral Load ◽

Term Survival ◽

Late Mortality ◽

Living With Hiv

Abstract Background Histoplasmosis is a common opportunistic infection afflicting people living with HIV (PLWH) globally. There are no data on long term survival of PLWH with histoplasmosis. Methods We conducted a single-center retrospective cohort study of PLWH diagnosed with histoplasmosis between 2002 and 2017. Data collected included demographics, clinical characteristics, treatment, and mortality. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death within 90 days), late mortality (death at or after 90 days), and survivors. Between group differences in demographic and clinical characteristics were assessed using Chi square for categorical variables and Mann-Whitney U non-parametric tests for continuous variables. Mortality was compared using Cox proportional hazards. Insurance type (i.e. private versus public option) served as a surrogate indicator of socioeconomic status (SES). Patients diagnosed with histoplasmosis in or after 2008 were considered a part of the modern ART era, regardless of treatment regimen. Results Our review found 54 PLWH infected with histoplasmosis from 2002-2017. Overall mortality was 37%, with 14.8% early mortality and 22.2% late mortality. Median survival time in the early mortality group was 13.5 days (IQR 2.5-41 days), and 338 days (IQR 180.5-803.3) in the late mortality group. Compared to the late mortality group, survivors were over 6 times more likely to have suppressed HIV viral load at last observation (HR 6.19, p=0.013). Median HIV viral load at last observation was lower among the survivors (2 log copies/ml, IQR 0, 4.5) compared to the late mortality group (4.1 log copies/ml, IQR 2.6,5.5) (p=0.010). Survivors were twice as likely to have private insurance, but this did not reach statistical significance (HR 2.19, p=0.14). There was no statistically significant difference in survival based on the availability of modern ART (p=0.85). The year of diagnosis made no difference with regards to survival (p=0.914). Baseline Characteristics of PLWH with Histoplasmosis HIV-related Characteristics of PLWH with Histoplasmosis Conclusion Histoplasmosis continues to be associated with high mortality among PLWH. Improved long-term survival is seen in patients with suppressed HIV viral loads. Disclosures Andrej Spec, MD, MSCI, Astellas (Grant/Research Support)Mayne (Consultant)Scynexis (Consultant)

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Correlation between Cepheid GeneXpert and Abbott M2000 assays for HIV viral load measurements

International Journal of STD & AIDS ◽

10.1177/0956462420975606 ◽

2021 ◽

pp. 095646242097560

Author(s):

Kaveh Manavi ◽

James Hodson ◽

Sindiso Masuka ◽

Mebie Singo ◽

Katie Dedicoat ◽

...

Keyword(s):

Viral Load ◽

Standard Of Care ◽

Continuous Variable ◽

People Living With Hiv ◽

Limits Of Agreement ◽

Hiv Viral Load ◽

The Mean ◽

Highly Correlated ◽

A Prospective Study ◽

Living With Hiv

Measurement of HIV viral load (VL) is the best indicator of success of antiretroviral therapy. We investigated the correlation between results by the Cepheid GeneXpert and a standard of care VL assay (Abbott M2000). This was a prospective study of people living with HIV who attended the department for routine VL measurement with the Abbott M2000. Consenting patients agreed to provide one extra blood sample for VL measurement with the Cepheid GeneXpert assay. One hundred patients consented to participate in the study. There were 18 patients with VL ≥ 40 copies/mL and 75 patients with VL < 40 copies on both assays. The two assays had 93% agreement, with a kappa of 0.79 ( p < 0.001). Treating VL as a continuous variable found measurements to be significantly higher on the Cepheid GeneXpert assay than the Abbott ( p = 0.002). Analysis of samples with VL ≥ 40 copies/mL on either assay ( n = 25) found the mean difference between the two assays to be 0.31 log10 copies/mL (95% limits of agreement: −0.63, 1.25). Whilst the measurements on the two assays are relatively highly correlated, there is a clear bias, with the Cepheid GeneXpert tending to give higher VL values.

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