scholarly journals Peripheral blood CD4+CCR6+ compartment differentiates HIV-1 infected or seropositive elite controllers from long-term successfully treated individuals

2021 ◽  
Author(s):  
Sara Svensson Akusjärvi ◽  
Shuba Krishnan ◽  
Bianca Jütte ◽  
Anoop Ambikan ◽  
Soham Gupta ◽  
...  
Keyword(s):  
Viral Suppression ◽  
People Living With Hiv ◽  
Elite Controllers ◽  
Receptor Profile ◽  
Increased Sensitivity ◽  
Cell Death Mechanisms ◽  
Living With Hiv ◽  
Negative Controls ◽  
Hiv 1

Abstract HIV-1 infection induces a chronic inflammatory environment not restored by suppressive antiretroviral therapy (ART). As of today, the effect of viral suppression and immune reconstitution in people living with HIV-1 (PLWH) on long-term suppressive ART (PLWHART) is not well-described. Herein, we show how PLWH who naturally control the virus (PLWHEC) have a reduced proportion of CD4+CCR6+ cells compared to PLWHART and HIV-1 negative controls. Specifically, the CD4+CCR6+/CCR6- cells exhibited a uniqe proteomic profile with a modulated energy metabolism in PLWHEC compared to PLWHART independent of CCR6 status. Furthermore, the CD4+CCR6+ cells were enriched in proteins involved in apoptosis and p53 signalling in PLWHEC compared to PLWHART, indicative of increased sensitivity towards cell death mechanisms. Collectively, this data shows how PLWHEC have a unique chemokine receptor profile that may aid in facilitating natural control of HIV-1 infection.

Classes of Antiretrovirals

2017 ◽  
Author(s):  
Benjamin Young
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Hiv Protease ◽  
People Living With Hiv ◽  
Hiv Integrase ◽  
Combination Antiretroviral Therapy ◽  
Entry Inhibitors ◽  
Asymptomatic Individuals ◽  
Living With Hiv ◽  
Hiv 1

Results of the randomized, international INSIGHT START clinical trial provide definitive proof of the benefit of antiretroviral therapy initiation in asymptomatic individuals with CD4+ counts greater than 500 cells/mm3. There are six different classes of antiretroviral agents: two types of reverse transcriptase inhibitors, two types of entry inhibitors, one class of inhibitors of HIV protease, and one class of inhibitors of HIV integrase. Combination antiretroviral therapy is recommended for all people living with HIV. The primary goal of combination antiretroviral therapy is to achieve viral suppression. Each antiretroviral class targets a unique step in the replication cycle of HIV-1.

scholarly journals Antiretroviral Therapy Dampens Mucosal CD4+ T Lamina Propria Lymphocytes Immune Activation in Long-Term Treated People Living with HIV-1

2021 ◽  
Vol 9 (8) ◽  
pp. 1624
Author(s):  
Alessandro Lazzaro ◽  
Giuseppe Pietro Innocenti ◽  
Letizia Santinelli ◽  
Claudia Pinacchio ◽  
Gabriella De Girolamo ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Lamina Propria ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
People Living With Hiv ◽  
Living With Hiv ◽  
Lamina Propria Lymphocytes ◽  
Hiv 1

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.

scholarly journals Use of rilpivirine in HIV-1-infected individuals in routine clinical practice from 2012 to 2017 in France

2020 ◽  
Author(s):  
Valérie Potard ◽  
Sebastien Gallien ◽  
Ana Canestri ◽  
Dominique Costagliola ◽  
S Abel ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Viral Suppression ◽  
People Living With Hiv ◽  
Loss To Follow Up ◽  
Virological Success ◽  
Virological Outcomes ◽  
Treatment Switch ◽  
Living With Hiv ◽  
Hiv 1

Abstract Objectives We assessed virological outcomes of rilpivirine use in France from 2012 to 2017, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to rilpivirine while failing therapy; and (iii) ARV-experienced PLHIV switching to rilpivirine while virologically controlled. Methods Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering rilpivirine discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. Results Among the 2166 ARV-naive PLHIV initiating rilpivirine, the 4 year cumulative incidence of VS was 91.0% and was associated with baseline VL. Among the 2125 ARV-experienced PLHIV switching to rilpivirine while failing therapy, the 4 year cumulative incidence of VS was 82.5% and was associated with lower VL, higher CD4 and less than three prior ARVs. Among the 11 828 ARV-experienced PLHIV switching to rilpivirine while virologically controlled, the 4 year cumulative incidence of VF was 9.6%. The risk of VF was lower among MSM, for PLHIV with CD4 ≥ 500 cell/mm3, without a prior AIDS event, or with a longer VL suppression at baseline. Conclusions Rilpivirine-containing regimens yielded high rates of viral suppression in most participants, while it was ineffective when used outside the marketing authorization in naive participants.

scholarly journals Excess burden of age-associated comorbidities among people living with HIV in British Columbia, Canada: a population-based cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041734
Author(s):  
Ni Gusti Ayu Nanditha ◽  
Adrianna Paiero ◽  
Hiwot M Tafessu ◽  
Martin St-Jean ◽  
Taylor McLinden ◽  
...  
Keyword(s):  
British Columbia ◽  
Cohort Study ◽  
Population Based ◽  
Age At Diagnosis ◽  
Secondary Outcome ◽  
People Living With Hiv ◽  
Prevalence Trends ◽  
Living With Hiv ◽  
Negative Controls ◽  
Hiv Negative

ObjectivesAs people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV.Design and settingThis population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 1:4 age-sex-matched HIV-negative individuals in British Columbia, Canada.ParticipantsThe study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012.Primary and secondary outcome measuresThe presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer’s and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests compared the age at diagnosis of comorbidities stratified by rate of healthcare encounters.ResultsAcross study period, the prevalence of all chronic age-associated comorbidities, except hypertension, were higher among PLWH compared with their community-based HIV-negative counterparts; as much as 10 times higher for liver diseases (25.3% vs 2.1%, p value<0.0001). On stratification by healthcare encounter rates, PLWH experienced most chronic age-associated significantly earlier than HIV-negative controls, as early as 21 years earlier for Alzheimer’s and/or dementia.ConclusionsPLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.

scholarly journals Antiretroviral Drugs Impact Autophagy with Toxic Outcomes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman
Keyword(s):  
Quality Control ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Viral Suppression ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Foreign Material ◽  
Complete Understanding ◽  
Living With Hiv ◽  
Target Effects

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.

scholarly journals HIV-1 subverts the complement system in semen to enhance viral transmission

2021 ◽  
Author(s):  
Bernadien M. Nijmeijer ◽  
Marta Bermejo-Jambrina ◽  
Tanja M. Kaptein ◽  
Carla M. S. Ribeiro ◽  
Doris Wilflingseder ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Virus Transmission ◽  
Sexual Contact ◽  
Target Cells ◽  
People Living With Hiv ◽  
Lectin Receptor ◽  
Pre Treatment ◽  
Living With Hiv ◽  
Hiv 1

AbstractSemen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

scholarly journals Clinical situation of Venezuelan migrants living with HIV in a hospital in Lima, Peru

2021 ◽  
pp. 095646242110240
Author(s):  
Genesis S Huerta-Vera ◽  
Manuel A Amarista ◽  
Fernando A Mejía ◽  
Ana B Graña ◽  
Elsa V Gonzalez-Lagos ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Clinical Situation ◽  
Cross Sectional Study ◽  
People Living With Hiv ◽  
Sectional Study ◽  
Cross Sectional ◽  
Epidemiological Trends ◽  
Clinical Conditions ◽  
Living With Hiv

Due to a huge crisis extensive to health services many Venezuelan people living with HIV (PLWH) had migrated abroad, including Peru where favorable laws were in place until June 2019. We describe the health status and epidemiological trends of PLWH from Venezuela at an HIV program in Lima. We analyzed baseline and follow-up data of all Venezuelan PLWH enrolled in our HIV program from January 2017 to December 2019. A cross-sectional study in a subsample served to describe ARV adherence and context of migration. Between 2017-2019 our HIV Program registered 398 Venezuelan PLWH, representing 20% of the 2018 annual enrollments; numbers decreased since mid-2019. The median age was 30 years (IQR 26;37) and 90.5% were men. Between 2017 and 2019, the proportion with diagnosis in Peru increased from 14.3% to 60.9%; of AIDS stage at entry, from 8.8% to 27.2%. By December 2019, 182/250 (72.8%) were still in care, and 43 (10.8%) had not started ART. Viral suppression evaluated in 195, was achieved in 71.8%. From 2017 to 2019, migrant PLWH arrived in worsened clinical conditions, with increasing diagnosis in Peru; the flow of migrant PLWH entering care diminished with less favorable laws. Viral suppression rates were suboptimal.

scholarly journals Substance use, Unlike Dolutegravir, is Associated with Mood Symptoms in People Living with HIV

2021 ◽  
Author(s):  
Lisa Van de Wijer ◽  
Wouter van der Heijden ◽  
Mike van Verseveld ◽  
Mihai Netea ◽  
Quirijn de Mast ◽  
...  
Keyword(s):  
Substance Use ◽  
Term Treatment ◽  
Assessment Tools ◽  
Self Report ◽  
People Living With Hiv ◽  
Antiretroviral Drug ◽  
Long Term Treatment ◽  
Living With Hiv ◽  
Neuropsychiatric Side Effects

AbstractContradictory data have been reported concerning neuropsychiatric side effects of the first-line antiretroviral drug dolutegravir, which may be partly due to lack of control groups or psychiatric assessment tools. Using validated self-report questionnaires, we compared mood and anxiety (DASS-42), impulsivity (BIS-11), and substance use (MATE-Q) between dolutegravir-treated and dolutegravir-naive people living with HIV (PLHIV). We analyzed 194, mostly male, PLHIV on long-term treatment of whom 82/194 (42.3%) used dolutegravir for a median (IQR) of 280 (258) days. Overall, 51/194 (26.3%) participants reported DASS-42 scores above the normal cut-off, 27/194 (13.5%) were classified as highly impulsive, and 58/194 (29.9%) regularly used recreational drugs. Regular substance use was positively associated with depression (p = 0.012) and stress scores (p = 0.045). We observed no differences between dolutegravir-treated and dolutegravir-naive PLHIV. Our data show that depressed and anxious moods and impulsivity are common in PLHIV and associate with substance use and not with dolutegravir use.

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