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

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 950
Author(s):  
Bonolo B. Phinius ◽  
Motswedi Anderson ◽  
Lynnette Bhebhe ◽  
Kabo Baruti ◽  
Godiraone Manowe ◽  
...  

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.

2020 ◽  
Author(s):  
Maya Mellor ◽  
Anne Bast ◽  
Nicholas Jones ◽  
Nia Roberts ◽  
Jose Ordonez-Mena ◽  
...  

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.


2020 ◽  
Author(s):  
Chloe A Teasdale ◽  
Cecilia Hernandez ◽  
Allison Zerbe ◽  
Duncan Chege ◽  
Mark Hawken ◽  
...  

Abstract Background: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV(PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers.Methods: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between HIV viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to six months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at six months is reported on the log10 scale and as percentage change from baseline.Results: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (>500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p<0.0001), female sex (p=0.02) and tuberculosis (p=-0.02). After six months on ART, 518 (84.8%) PLHIV had achieved viral load <1,000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to six months was -0.12 (95%CI -0.15, - 0.09) (p<0.0001) indicating at 31.3% decline (95%CI -40.0, -23.0) in D-dimer levels over the first six months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (-172.1%, 95%CI -259.0, -106.3; p<0.0001) and those with log viral load >6.0 copies/mL (-91.1%, 95%CI -136.7, -54.2; p<0.01). Conclusions: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at six months in this large African cohort.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Anita Mesic ◽  
Alexander Spina ◽  
Htay Thet Mar ◽  
Phone Thit ◽  
Tom Decroo ◽  
...  

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.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Alhanoof Alohaly ◽  
Adriana Campa ◽  
Leslie Seminario ◽  
Marianna Baum

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.


AIDS Care ◽  
2020 ◽  
pp. 1-8
Author(s):  
Deepika E. Slawek ◽  
Julia Arnsten ◽  
Nancy Sohler ◽  
Chenshu Zhang ◽  
Robert Grossberg ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255834
Author(s):  
Bogusz Jan Aksak-Wąs ◽  
Miłosz Parczewski ◽  
Anna Urbańska ◽  
Małgorzata Hackiewicz ◽  
Justyna D. Kowalska

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.


2021 ◽  
Author(s):  
Khadija Khan ◽  
Gila Lustig ◽  
Mallory Bernstein ◽  
Derseree Archary ◽  
Sandile Cele ◽  
...  

Background People living with HIV (PLWH) have been reported to have an increased risk of more severe Covid-19 disease outcome and an increased risk of death relative to HIV-uninfected individuals. Here we assessed the ability of the Johnson and Johnson Ad26.CoV2.S vaccine to elicit neutralizing antibodies to the Delta variant in PLWH relative to HIV-uninfected individuals. Methods We enrolled 26 PLWH and 73 HIV-uninfected participants from the SISONKE phase 3b open label South African clinical trial of the Ad26.CoV2.S vaccine in health care workers (HCW) in a prospective observational cohort study. Enrollment was a median 56 days (range 19-98 days) post-vaccination. HCW PLWH had well suppressed HIV viremia. As a comparison, we also enrolled unvaccinated participants previously infected with SARS-CoV-2. This group consisted of 34 PLWH and 28 HIV-uninfected individuals. We used the presence of SARS-CoV-2 nucleocapsid antibodies and any previous record of SARS-CoV-2 infection to differentiate the vaccinated participants into participants who were previously infected with SARS-CoV-2 and those not previously infected. Neutralization capacity was assessed using participant plasma in a live virus neutralization assay of the Delta SARS-CoV-2 variant currently dominating infections in South Africa. This study was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001275/2020). Findings Unvaccinated PLWH showed 6-fold reduced neutralization of the Delta variant relative to HIV-uninfected participants (GMT=105 for HIV-uninfected, 15 for PLWH, p=0.001). The majority (68%) of Ad26.CoV2.S vaccinated HCW were found to be previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared to the infected only group (GMT of 306 versus 36) and 26-fold higher relative to the vaccinated only group (GMT=12). There was no significant difference in Delta variant neutralization in vaccinated and previously SARS-CoV-2 infected PLWH relative to vaccinated and previously SARS-CoV-2 infected, HIV-uninfected participants (GMT of 300 for PLWH versus 307 for HIV-uninfected). Vaccinated only participants showed a low neutralization of the Delta variant, with a stronger response in PLWH (GMT=73, for PLWH, 6 for HIV-uninfected, p=0.02). Interpretation While PLWH showed reduced neutralization of the Delta variant following SARS-CoV-2 infection, the neutralization response following Ad26.CoV2.S vaccination was not inferior to HIV-uninfected study participants. Funding South African Medical Research Council, The Bill & Melinda Gates Foundation.


Author(s):  
Ditte Marie Kirkegaard-Klitbo ◽  
Flemming Bendtsen ◽  
Jens Lundgren ◽  
Robert J de Knegt ◽  
Klaus Fuglsang Kofoed ◽  
...  

Abstract Background Liver fibrosis is associated with poor liver related outcomes and mortality. People living with HIV (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls. Methods Cross-sectional cohort study. We compared 342 PWH with 2,190 population controls aged 50-70 years. Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were computed by logistic regression. Results The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%), p&lt;0.01). HIV infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR:1.84 (1.17;2.88), p&lt;0.01); higher age (per decade, aOR:3.34 (1.81;6.18), p&lt;0.01); ALT (per 10 IU/L, aOR:1.25 (1.05;1.49), p&lt;0.01); BMI (per 1 kg/m 2, aOR:1.17 (1.05;1.29), p&lt;0.01) and previous exposure to didanosine (per year aOR:2.26 (1,01;5.06), p=0.05). Conclusions The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine and a positive HIV status was independently associated with higher odds of elevated LSM.


2021 ◽  
pp. 095646242110552
Author(s):  
Mohammad Zubair Harooni ◽  
Abdul Alim Atarud ◽  
Ehsanullah Ehsan ◽  
Ajmal Alokozai ◽  
Willi McFarland ◽  
...  

Background Afghanistan adopted a “test and treat” strategy for all people living with HIV (PLWH) in 2016. In this study, we presented demographic and clinical characteristics of all people diagnosed between 2013 and 2019 and evaluated progress towards 90-90-90 UNAIDS targets and identified program gaps among PLWH in Afghanistan diagnosed in 2018. Methods We used clinical, behavioral, and demographic data from national HIV surveillance for 1394 patients diagnosed from 2013 through 2019. We also tracked 184 patients diagnosed with HIV in 2018 over 15 months to assess their enrollment in care, antiretroviral therapy (ART) initiation, retention on ART, and viral suppression. Results Of 1394 patients diagnosed from 2013 through 2019, 76.0% were male, 73.7% were older than 24 years, and 33.4% acquired HIV through heterosexual sex. Of the 184 patients diagnosed in 2018, 94.6% were enrolled in care, 88.6% received ART, 84.2% were retained on ART for at least 12 months, and 33.7% received a viral load test. Of those with a viral load test, 74.2% were virally suppressed. Patients who were 35–44 years old (52.0%, p-value .001), acquired HIV through unsafe injection (62.5%, p-value .413), were co-infected with hepatitis C virus (HCV) (60.0%, p-value .449), and with CD4 > 500 at diagnosis (64.7%, p-value .294) were less likely to be virally suppressed 12 months after diagnosis. Conclusion Nearly 95% of people diagnosed with HIV in Afghanistan in 2018 were linked to care and nearly 90% were on ART. Viral testing and viral suppression remain low with notable disparities for middle-aged patients, and possibly for those who injected drugs. Addressing barriers to HIV programs in Afghanistan, particularly for people who inject drugs (PWID), are urgently needed to reach the 90-90-90 global targets. Surveillance data on the number of people with undiagnosed HIV is needed to assess the first 90 target.


2019 ◽  
Vol 57 (4) ◽  
Author(s):  
Minh D. Pham ◽  
Berhan A. Haile ◽  
Iskandar Azwa ◽  
Adeeba Kamarulzaman ◽  
Nishaan Raman ◽  
...  

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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