Asymptomatic Human Immunodeficiency Virus-1 Infection with High CD4+ T Cell Count Does Not Alter Iron Metabolism or Hepcidin Levels: The Pilot Study

Abstract Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.

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Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw118 ◽

2016 ◽

Vol 3 (3) ◽

Cited By ~ 10

Author(s):

Ashwin Balagopal ◽

Nikhil Gupte ◽

Rupak Shivakoti ◽

Andrea L. Cox ◽

Wei-Teng Yang ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Interferon Γ ◽

Cd4 T Cell ◽

Clinical Failure ◽

Immunodeficiency Virus ◽

Ifn Γ ◽

Cd4 T Cell Count

Abstract Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

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CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus

Cancer ◽

10.1002/cncr.9016 ◽

2001 ◽

Vol 93 (2) ◽

pp. 111-114 ◽

Cited By ~ 29

Author(s):

Marina Cardillo ◽

Robert Hagan ◽

Jacobo Abadi ◽

Maria A. Abadi

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

T Cell ◽

Cell Count ◽

Cd4 T Cell ◽

Squamous Intraepithelial Lesions ◽

Immunodeficiency Virus ◽

Intraepithelial Lesions ◽

Cd4 T Cell Count

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Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw219 ◽

2017 ◽

Vol 4 (1) ◽

Cited By ~ 8

Author(s):

Enrico G. Ferro ◽

Gabriel J. Culbert ◽

Jeffrey A. Wickersham ◽

Ruthanne Marcus ◽

Alana D. Steffen ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

People Who Inject Drugs ◽

Cd4 T Cell ◽

Key Populations ◽

Incidence And Mortality ◽

Immunodeficiency Virus ◽

Cd4 T Cell Count

Abstract Background Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.

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Pharmacokinetics of itraconazole (oral solution) in two groups of human immunodeficiency virus-infected adults with oral candidiasis.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.11.2554 ◽

1997 ◽

Vol 41 (11) ◽

pp. 2554-2558 ◽

Cited By ~ 35

Author(s):

J Reynes ◽

C Bazin ◽

F Ajana ◽

A Datry ◽

J P Le Moing ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Cell Count ◽

Oral Candidiasis ◽

Oral Solution ◽

Cd4 T Cell ◽

Pharmacokinetic Parameters ◽

Time Curve ◽

Immunodeficiency Virus ◽

Cd4 T Cell Count

The pharmacokinetics of itraconazole formulated in a hydroxypropyl-beta-cyclodextrin oral solution was determined for two groups of human immunodeficiency virus (HIV)-infected adults with oral candidiasis (group A, 12 patients with CD4+ T-cell count of >200/mm3 and no AIDS, and group B, 11 patients with CD4+ T-cell count of <100/mm3 and AIDS). Patients received 100 mg of itraconazole every 12 h for 14 days. Concentrations of itraconazole and hydroxyitraconazole, the main active metabolite, were measured in plasma and saliva by high-performance liquid chromatography. Pharmacokinetic parameters determined at days 1 and 14 (the area under the concentration-time curve from 0 to 10 h, the maximum concentration of drug in plasma [Cmax], and the time to Cmax) were comparable in both groups. Trough levels in plasma (Cmin) were similar in both groups for the complete duration of the study. An effective concentration of itraconazole in plasma (>250 ng/ml) was reached at day 4. At day 14, Cmin values of itraconazole were 643 +/- 304 and 592 +/- 401 ng/ml for groups A and B, respectively, and Cmin values of hydroxyitraconazole were 1,411 +/- 594 and 1,389 +/- 804 ng/ml for groups A and B, respectively. In saliva, only unchanged itraconazole was detected, and mean concentrations were still high (>250 ng/ml) 4 h after the intake, which may contribute to the fast clinical response. In conclusion, the oral solution of itraconazole generates effective levels in plasma and saliva in HIV-infected patients; its relative bioavailability is not modified by the stage of HIV infection.

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A Subset of Extreme Human Immunodeficiency Virus (HIV) Controllers Is Characterized by a Small HIV Blood Reservoir and a Weak T-Cell Activation Level

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx064 ◽

2017 ◽

Vol 4 (2) ◽

Cited By ~ 22

Author(s):

Etienne Canouï ◽

Camille Lécuroux ◽

Véronique Avettand-Fenoël ◽

Marine Gousset ◽

Christine Rouzioux ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

T Cell ◽

Cell Count ◽

T Cell Activation ◽

Cell Activation ◽

Cd4 T Cell ◽

Hiv Dna ◽

Immunodeficiency Virus ◽

Cd4 T Cell Count

Abstract Background Human immunodeficiency virus controllers (HICs) form a heterogeneous group of patients with regard to formal definitions, immunologic characteristics, and changes over time in viral load. Patients and Methods The HICs with undetectable viral load ([uHICs] ie, for whom a viral load had never been detected with routine assays; n = 52) were compared with 178 HICs with blips during the follow up (bHICs). Clinical characteristics, ultrasensitive HIV-ribonucleic acid (RNA) and HIV-deoxyribonucleic acid (DNA) loads, HIV1-Western blot profiles, and immune parameters were analyzed. Results Relative to bHICs, uHICs had significantly lower ultrasensitive plasma HIV-RNA loads (P < .0001) and HIV-DNA levels in peripheral blood mononuclear cells (P = .0004), higher CD4+ T-cell count (P = .04) at enrollment, and lower T-cell activation levels. Between diagnosis and inclusion in the cohort, the CD4+ T-cell count had not changed in uHICs but had significantly decreased in bHICs. Twenty-one percent of the uHICs lacked specific anti-HIV immunoglobulin G antibodies, and these individuals also had very low levels of HIV-DNA. Half of the uHICs had a protective human leukocyte antigen (HLA) allele (-B57/58/B27), a weak CD8+ T-cell response, and very small HIV-DNA reservoir. Conclusions We suggest that an interesting HIC phenotype combines protective HLA alleles, low level of HIV blood reservoirs, and reduced immune activation. Prospective studies aimed at evaluating the benefit of combined antiretroviral therapy in HICs might take into account the identification of uHICs and bHICs.

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Once-daily Doravirine in Human Immunodeficiency Virus Type 1–Infected, Antiretroviral-naive Adults: An Integrated Efficacy Analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciz424 ◽

2019 ◽

Vol 70 (7) ◽

pp. 1344-1352 ◽

Cited By ~ 1

Author(s):

Chloe Orkin ◽

Jean-Michel Molina ◽

Johan Lombaard ◽

Edwin DeJesus ◽

Anthony Rodgers ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Cell Count ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 T Cell ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Cd4 T Cell Count

AbstractBackgroundDoravirine (DOR) demonstrated noninferior efficacy to darunavir plus ritonavir (DRV+r) and efavirenz (EFV) in 2 ongoing phase 3 trials: DRIVE-FORWARD (NCT02275780) and DRIVE-AHEAD (NCT02403674).MethodsThis prespecified analysis pooled efficacy data through the first 48 weeks of DRIVE-FORWARD and DRIVE-AHEAD from the DOR groups (DOR/lamivudine [3TC]/tenofovir disoproxil fumarate [TDF] or DOR [100 mg daily] with emtricitabine [FTC]/TDF or abacavir [ABC]/3TC [n = 747]) compared with DRV+r (800/100 mg daily) with FTC/TDF or ABC/3TC (n = 383) or EFV/FTC/TDF (600/200/300 mg daily; n = 364). Efficacy assessments included the proportion of participants with human immunodeficiency virus type 1 (HIV-1) RNA <50 copies/mL and change in CD4+ T-cell count.ResultsAt week 48, DOR demonstrated noninferior efficacy to DRV+r and EFV, with 84.1% of DOR-treated participants achieving HIV-1 RNA <50 copies/mL compared with 79.9% of the DRV+r and 80.8% of the EFV groups. Results were similar across demographic/prognostic subpopulations, including baseline plasma HIV-1 RNA, gender, race, and HIV-1 subtype. Mean increases from baseline in CD4+ T-cell count through 48 weeks were 195.5 cells/mm3 for DOR, 185.6 cells/mm3 for DRV+r, and 188.4 cells/mm3 for EFV/FTC/TDF.ConclusionsDOR, as a single entity (in combination with other antiretroviral agents) and as a fixed-dose combination (DOR/3TC/TDF), demonstrated noninferior efficacy to DRV+r and EFV as assessed by the proportion of HIV-1-infected, treatment-naive adults with HIV-1 RNA <50 copies/mL.Clinical Trials RegistrationNCT02275780 and NCT02403674.

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