The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies—A perspective from US Medicaid data

2021 ◽  
pp. 095646242110528
Author(s):  
Wing Chow ◽  
Hélène Hardy ◽  
Ji Song ◽  
Nancy Connolly ◽  
Bingcao Wu
Keyword(s):  
Antiretroviral Therapy ◽  
Primary Outcome ◽  
Neuropsychiatric Disorders ◽  
Administrative Claims ◽  
Art Initiation ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
The Mean ◽  
Living With Hiv ◽  
Hiv 1

Background People with human immunodeficiency virus (HIV)-1 face challenges with treatment adherence for various reasons, including consideration of neuropsychiatric disorders and neuropsychiatric adverse reactions associated with antiretroviral therapy (ART). Methods A retrospective cohort study was conducted using administrative claims data from the IBM MarketScan® Multi-State Medicaid Database (1/1/2014–12/31/2017). Adults (≥18 years) diagnosed with HIV-1 and newly initiated on antiretroviral therapy with continuous health plan enrollment were included. Primary outcome was the 6-month period prevalence of neuropsychiatric events (NPEs) of interest after ART initiation. Results Among 1971 newly treated patients included in the study, mean age (standard deviation [SD]) was 38.5 (12.7) years, and 41.4% were female. During the 6 months after ART initiation, 51.4% of patients had a claim for ≥1 NPE versus 30.3% of matched patients without HIV. Among newly treated patients, the most common (≥10%) NPE claims were for depression (42.2%), anxiety (15.8%), headache (11.9%), and bipolar/manic depression (10.1%). Also in this group, the mean (SD) total all-cause healthcare cost during the 6-month post-ART initiation was $16,632 ($33,928), of which $2914 ($18,233) was NPE-related. Conclusions In summary, in this Medicaid study of people newly initiated on ART, there was a high prevalence of NPEs, and incremental NPE-associated costs were considerable.

scholarly journals Antiretroviral Therapy Initiation Is Associated With Decreased Visceral and Subcutaneous Adipose Tissue Density in People Living With Human Immunodeficiency Virus

2020 ◽  
Author(s):  
Paula Debroy ◽  
Jordan E Lake ◽  
Carlee Moser ◽  
Maxine Olefsky ◽  
Kristine M Erlandson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Human Immunodeficiency Virus ◽  
Adipose Tissue ◽  
Antiretroviral Therapy ◽  
Hdl Cholesterol ◽  
Cd4 T Cell ◽  
Art Initiation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background Adipose tissue (AT) alterations are common in people living with human immunodeficiency virus (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immunometabolic parameters. Methods In a prospective randomized clinical trial of ART initiation, L4–L5 abdominal CT scans measured subcutaneous AT (SAT) and visceral AT (VAT) area and density in treatment-naive PLWH randomized to tenofovir-emtricitabine plus ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Linear regression models compared week 0 and week 96 levels, and 96-week changes, in SAT and VAT density (in Hounsfield units [HU]). Spearman correlations assessed relationships between AT density and immunometabolic parameters. Results Of the 228 participants, 89% were male and 44% were white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense week 96 SAT and VAT density correlated with higher high-density lipoprotein (HDL) cholesterol and adiponectin (r = 0.19–0.30) levels and lower interleukin 6, non-HDL cholesterol, triglyceride, leptin, and homeostatic model assessment of insulin resistance (r = −0.23 to −0.68) levels at week 96 after adjusting for baseline CD4+ T-cell count, HIV-1 RNA, and baseline AT area. Conclusions Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances, and insulin resistance independent of AT area, suggesting that changes in AT density with ART may lead to adverse health outcomes independent of AT quantity. Clinical Trials Registration NCT00851799.

scholarly journals Early ART-initiation Reduces HIV-1 Proviral DNA Levels in Children from the CHER Trial

2021 ◽  
Author(s):  
Helen Payne ◽  
Man Chan ◽  
Sarah Watters ◽  
Kennedy Otwombe ◽  
Yuan Hsiao ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Factors Associated ◽  
Proviral Dna ◽  
Art Initiation ◽  
Latent Hiv ◽  
Dna Reduction ◽  
Living With Hiv ◽  
Hiv 1

Abstract BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: Infants with HIV <12 weeks old with CD4% ≥25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40W, ART-96W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40W/ART-96W, ART was started/re-started for clinical progression or CD4% <25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p=0.0003) and 248 weeks (p=0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p=0.0225) and 248 weeks (p=0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p=0.0042).INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure.FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

scholarly journals Viral Blip Dynamics during Highly Active Antiretroviral Therapy

2003 ◽  
Vol 77 (22) ◽  
pp. 12165-12172 ◽  
Author(s):  
Michele Di Mascio ◽  
Martin Markowitz ◽  
Michael Louie ◽  
Christine Hogan ◽  
Arlene Hurley ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Extended Period ◽  
Two Phase ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Specific Factors ◽  
The Mean ◽  
Hiv 1

ABSTRACT Although intermittent episodes of low-level viremia are often observed in well-suppressed highly active antiretroviral therapy (HAART)-treated patients, the timing and amplitude of viral blips have never been examined in detail. We analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50 copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years (range, 5 months to 5.3 years). The mean (± the standard deviation) blip frequency was 0.09 ± 0.11/sample, with about one-third of patients showing no viral blips. The mean viral blip amplitude was 158 ± 132 human immunodeficiency virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude distributions suggest that two blips less than 22 days apart have a significant chance of being part of the same episode of viremia. The data are consistent with a hypothetical model in which each episode of viremia consists of a phase of VL rise, followed by two-phase exponential decay. Thus, the term “viral blip” may be a misnomer, since viral replication appears to be occurring over an extended period. Neither the frequency nor the amplitude of viral blips increases with longer periods of observation, but the frequency is inversely correlated with the CD4+-T-cell count at the start of therapy, suggesting that host-specific factors but not treatment fatigue are determinants of blip frequency.

scholarly journals Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Helen Payne ◽  
Man K. Chan ◽  
Sarah A. Watters ◽  
Kennedy Otwombe ◽  
Nei-Yuan Hsiao ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Factors Associated ◽  
Proviral Dna ◽  
Art Initiation ◽  
Latent Hiv ◽  
Dna Reduction ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. Methods Infants with HIV  <  12 weeks old with CD4%  ≥  25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4%  <  25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received  ≥  24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. Findings Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0003) and 248 weeks (p  =  0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0225) and 248 weeks (p  =  0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p  =  0.0042). Intepretation Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure. Funding Wellcome Trust, National Institutes of Health, Medical Research Council.

scholarly journals HIV Infection and Related Mental Disorders

2021 ◽  
Vol 11 (2) ◽  
pp. 248
Author(s):  
Marina Nosik ◽  
Vyacheslav Lavrov ◽  
Oxana Svitich
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Mental Disorders ◽  
Hiv Infection ◽  
Current Knowledge ◽  
People Living With Hiv ◽  
Immunodeficiency Virus ◽  
Living With Hiv ◽  
The Impact ◽  
Hiv 1

Over the more than thirty-year period of the human immunodeficiency virus type 1 (HIV-1) epidemic, many data have been accumulated indicating that HIV infection predisposes one to the development of mental pathologies. It has been proven that cognitive disorders in HIV-positive individuals are the result of the direct exposure of the virus to central nervous system (CNS) cells. The use of antiretroviral therapy has significantly reduced the number of cases of mental disorders among people infected with HIV. However, the incidence of moderate to mild cognitive impairment at all stages of HIV infection is still quite high. This review describes the most common forms of mental pathology that occur in people living with HIV and presents the current concepts on the possible pathogenetic mechanisms of the influence of human immunodeficiency virus (HIV-1) and its viral proteins on the cells of the CNS and the CNS’s functions. This review also provides the current state of knowledge on the impact of the antiretroviral therapy on the development of mental pathologies in people living with HIV, as well as current knowledge on the interactions between antiretroviral and psychotropic drugs that occur under their simultaneous administration.

scholarly journals Evolution of Human Immunodeficiency Virus Type 1 (HIV-1) Resistance Mutations in Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) in HIV-1-Infected Patients Switched to Antiretroviral Therapy without NNRTIs

2004 ◽  
Vol 48 (1) ◽  
pp. 172-175 ◽  
Author(s):  
Véronique Joly ◽  
Diane Descamps ◽  
Gilles Peytavin ◽  
Fatiha Touati ◽  
France Mentre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Nnrti Resistance ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Hiv 1

ABSTRACT We studied the evolution of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations among 29 human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced virologic failure when receiving an NNRTI-containing regimen (nevirapine, delavirdine, or efavirenz) and subsequently switched to antiretroviral therapy without NNRTIs. Genotypic resistance was determined from plasma samples collected at the time of NNRTI withdrawal (baseline) and during follow-up. At baseline, 83% of patients had more than two thymidine analog resistance mutations (TAMs), and all had NNRTI resistance mutations. Mutations at codons 103, 181, and 190 were found in 62, 62, and 34% of the patients, respectively. Follow-up samples were available after a median time of 6 months in all patients and at 12 months in 22 patients. The mean number of resistance mutations to NNRTIs was significantly lower at months 6 (1.34 ± 1.04) and 12 (1.18 ± 1.05) than at month 0 (2.03 ± 1.02) (P < 0.009). The percentages of patients with at least one NNRTI resistance mutation were 100, 76, and 73% at baseline, month 6, and month 12, respectively (P < 0.0044). Overall, 70% of the patients had a mutation at codon 103 or 181 at month 12. The mean number of TAMs did not vary significantly during follow-up. Our data show that, in the context of maintained antiretroviral therapy, NNRTI resistance mutations persist in two-thirds of the patients in spite of NNRTI withdrawal. These results argue for the low impact of NNRTI resistance mutations on viral fitness and suggest that resistance mutations to different classes of drugs are associated on the same genome, at least in some of the resistant strains.

scholarly journals Impact of Raltegravir or Efavirenz on Cell-Associated Human Immunodeficiency Virus-1 (HIV-1) Deoxyribonucleic Acid and Systemic Inflammation in HIV-1/Tuberculosis Coinfected Adults Initiating Antiretroviral Therapy

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
Héloïse M Delagreverie ◽  
Claire Bauduin ◽  
Nathalie De Castro ◽  
Beatriz Grinsztejn ◽  
Marc Chevrier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Deoxyribonucleic Acid ◽  
Randomized Study ◽  
High Sensitivity ◽  
Open Label ◽  
Art Initiation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
D Dimer

Abstract Background In view of the fast viremia decline obtained with integrase inhibitors, we studied the respective effects of initiating efavirenz (EFV) or raltegravir (RAL)-based antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV)-1 deoxyribonucleic acid (DNA) levels and inflammation biomarkers in the highly inflammatory setting of advanced HIV-1 disease with tuberculosis (TB) coinfection. Methods We followed cell-associated HIV-1 DNA, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), soluble CD14 and D-Dimer levels for 48 weeks after ART initiation in the participants to the ANRS12-180 REFLATE-TB study. This phase II open-label randomized study included ART-naive people with HIV and TB treated with rifampicin to receive RAL 400 mg twice daily (RAL400), RAL 800 mg twice daily (RAL800) or EFV 600 mg QD with tenofovir and lamivudine. Results In 146 participants, the median (interquartile range [IQR]) week (W)0 HIV-1 DNA level was 4.7 (IQR, 4.3–5.1) log10 copies/106 CD4+, and the reduction by W48 was −0.8 log10 copies/106 CD4+ on EFV, −0.9 on RAL400, and −1.0 on RAL800 (P = .74). Baseline median (IQR) hsCRP, IL-6, sCD14, and D-Dimer levels were 6.9 (IQR, 3.3–15.6) mg/L, 7.3 (IQR, 3.5–12.3) pg/mL, 3221 (IQR, 2383–4130) ng/mL, and 975 (IQR, 535–1970) ng/mL. All biomarker levels decreased over the study: the overall W0–W48 mean (95% confidence interval) fold-change on ART was 0.37 (IQR, 0.28–0.48) for hsCRP, 0.42 (IQR, 0.35–0.51) for IL-6, 0.51 (IQR, 0.47–0.56) for sCD14, and 0.39 (IQR, 0.32–0.47) for D-Dimers. There were no differences in biomarker reduction across treatment arms. Conclusions In participants with HIV and TB, EFV, RAL400, or RAL800 effectively and equally reduced inflammation and HIV-1 DNA levels.

scholarly journals Emergence of Drug Resistance in Human Immunodeficiency Virus Type 1 Infected Patients from Pune, India, at the End of 12 Months of First Line Antiretroviral Therapy Initiation

ISRN AIDS ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rajesh T. Patil ◽  
Rajiv M. Gupta ◽  
Sourav Sen ◽  
Srikanth P. Tripathy ◽  
Devidas N. Chaturbhuj ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Virologic Failure ◽  
First Line ◽  
Nnrti Resistance ◽  
Art Initiation ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

Introduction. In India, 4,86,173 HIV infected patients are on first line antiretroviral therapy (ART) as of January 2012. HIV drug resistance (HIVDR) is drug and regimen-specific and should be balanced against the benefits of providing a given ART regimen. Material & Methods. The emergence of HIVDR mutations in a cohort of 100 consecutive HIV-1 infected individuals attending ART centre, on first line ART for 12 months, was studied. CD4+ T-cell counts and plasma HIV-1 RNA level were determined. Result. Out of the 100 HIV-1 infected individuals, 81 showed HIVDR prevention (HIV-1 RNA level < 1000/mL), while the remaining 19 had HIV-1 viral RNA level > 1000/mL. HIVDR genotyping was carried out for individuals with evidence of virologic failure (HIV-1 RNA level > 1000/mL). The most frequent NRTI-associated mutation observed was M184V, while K103N/S was the commonest mutation at NNRTI resistance position. Conclusion. Our study has revealed the emergence of HIVDR in HIV-1 infected patients at the end of 12 months of first line ART initiation. For NRTIs, the prevalence of HIVDR mutations was 9% and 10% for NNRTIs. Our findings will contribute information in evidence-based decision making with reference to first and second line ART delivery and prevention of HIVDR emergence.

scholarly journals Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

scholarly journals Estimates of the Time From Seroconversion to Antiretroviral Therapy Initiation Among People Newly Diagnosed With Human Immunodeficiency Virus From 2006 to 2015, New York City

2019 ◽  
Vol 71 (8) ◽  
pp. e308-e315
Author(s):  
McKaylee M Robertson ◽  
Sarah L Braunstein ◽  
Donald R Hoover ◽  
Sheng Li ◽  
Denis Nash
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Hiv Testing ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Population Based ◽  
Cd4 Count ◽  
Hiv Diagnosis ◽  
Art Initiation ◽  
Immunodeficiency Virus

Abstract Background We estimated the time from human immunodeficiency virus (HIV) seroconversion to antiretroviral therapy (ART) initiation during an era of expanding HIV testing and treatment efforts. Methods Applying CD4 depletion parameters from seroconverter cohort data to our population-based sample, we related the square root of the first pretreatment CD4 count to time of seroconversion through a linear mixed model and estimated the time from seroconversion. Results Among 28 162 people diagnosed with HIV during 2006–2015, 89% initiated ART by June 2017. The median CD4 count at diagnosis increased from 326 (interquartile range [IQR], 132–504) cells/µL to 390 (IQR, 216–571) cells/µL from 2006 to 2015. The median time from estimated seroconversion to ART initiation decreased by 42% from 6.4 (IQR, 3.3–11.4) years in 2006 to 3.7 (IQR, 0.5–8.3) years in 2015. The time from estimated seroconversion to diagnosis decreased by 28%, from a median of 4.6 (IQR, 0.5–10.5) years to 3.3 (IQR, 0–8.1) years from 2006 to 2015, and the time from diagnosis to ART initiation reduced by 60%, from a median of 0.5 (IQR, 0.2–2.1) years to 0.2 (IQR, 0.1–0.3) years from 2006 to 2015. Conclusions The estimated time from seroconversion to ART initiation was reduced in tandem with expanded HIV testing and treatment efforts. While the time from diagnosis to ART initiation decreased to 0.2 years, the time from seroconversion to diagnosis was 3.3 years among people diagnosed in 2015, highlighting the need for more effective strategies for earlier HIV diagnosis.

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