scholarly journals Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure

2019 ◽  
Vol 71 (7) ◽  
pp. 1726-1731 ◽  
Author(s):  
Edward Mpoza ◽  
Radha Rajasingham ◽  
Lillian Tugume ◽  
Joshua Rhein ◽  
Maria Sarah Nabaggala ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cryptococcal Meningitis ◽  
Virologic Failure ◽  
Cost Effective ◽  
World Health ◽  
Load Testing ◽  
Viral Loads ◽  
Immunodeficiency Virus

Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. Conclusions In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

scholarly journals Discordant Outcomes following Failure of Antiretroviral Therapy Are Associated with Substantial Differences in Human Immunodeficiency Virus-Specific Cellular Immunity

2003 ◽  
Vol 77 (10) ◽  
pp. 6041-6049 ◽  
Author(s):  
David A. Price ◽  
George Scullard ◽  
Annette Oxenius ◽  
Ruth Braganza ◽  
Simon A. Beddows ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
T Lymphocyte ◽  
Virologic Failure ◽  
Multiple Drug Resistance ◽  
Testable Hypothesis ◽  
Plasma Virus ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Many individuals chronically infected with human immunodeficiency virus type 1 (HIV-1) experience a recrudescence of plasma virus during continuous combination antiretroviral therapy (ART) due either to the emergence of drug-resistant viruses or to poor compliance. In most cases, virologic failure on ART is associated with a coincident decline in CD4+ T lymphocyte levels. However, a proportion of discordant individuals retain a stable or even increasing CD4+ T lymphocyte count despite virological failure. In order to address the nature of these different outcomes, we evaluated virologic and immunologic variables in a prospective, single-blinded, nonrandomized cohort of 53 subjects with chronic HIV-1 infection who had been treated with continuous ART and monitored intensively over a period of 19 months. In all individuals with detectable viremia on ART, multiple drug resistance mutations with similar impacts on viral growth kinetics were detected in the pol gene of circulating plasma virus. Further, C2V3 env gene analysis demonstrated sequences indicative of CCR5 coreceptor usage in the majority of those with detectable plasma viremia. In contrast to this homogeneous virologic pattern, comprehensive screening with a range of antigens derived from HIV-1 revealed substantial immunologic differences. Discordant subjects with stable CD4+ T lymphocyte counts in the presence of recrudescent virus demonstrated potent virus-specific CD4+ and CD8+ T lymphocyte responses. In contrast, subjects with virologic failure associated with declining CD4+ T lymphocyte counts had substantially weaker HIV-specific CD4+ T lymphocyte responses and exhibited a trend towards weaker HIV-specific CD8+ T lymphocyte responses. Importantly the CD4+ response was sustained over periods as long as 11 months, confirming the stability of the phenomenon. These correlative data lead to the testable hypothesis that the consequences of viral recrudescence during continuous ART are modulated by the HIV-specific cellular immune response.

Impact of Viral Load Testing on Patient Care

1999 ◽  
Vol 123 (11) ◽  
pp. 1011-1014
Author(s):  
Frederick S. Nolte
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Modern Medicine ◽  
Load Testing ◽  
Hiv Rna ◽  
Viral Load Testing ◽  
Immunodeficiency Virus ◽  
Standard Of Practice ◽  
Hiv Type 1

Abstract Quantitative human immunodeficiency virus (HIV) type 1 RNA tests have been essential tools in increasing our understanding of HIV pathogenesis and antiretroviral therapy. The plasma HIV RNA level is among the most powerful predictive tests in modern medicine for disease progression and has rapidly become the standard of practice for guiding clinicians in initiating, monitoring, and changing antiretroviral therapy. In this article the scientific rationale and clinical indications for viral load testing in HIV infection are reviewed.

scholarly journals Decreased Bone Formative and Enhanced Resorptive Markers in Human Immunodeficiency Virus Infection: Indication of Normalization of the Bone-Remodeling Process during Highly Active Antiretroviral Therapy1

1999 ◽  
Vol 84 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Pål Aukrust ◽  
Charlotte J. Haug ◽  
Thor Ueland ◽  
Egil Lien ◽  
Fredrik Müller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Highly Active Antiretroviral Therapy ◽  
Serum Concentrations ◽  
Marked Rise ◽  
Highly Active ◽  
Immunodeficiency Virus

As cytokines and 1,25-dihydroxyvitamin D [1,25-(OH)2D] appear to have an important role in bone homeostasis, we examined the possibility that human immunodeficiency virus (HIV)-infected patients, characterized by enhanced levels of proinflammatory cytokines and 1,25-(OH)2D deficiency, have disturbed bone metabolism by analyzing serum markers of bone formation (osteocalcin) and bone resorption (C-telopeptide) in 73 HIV-infected patients. HIV-infected patients with advanced clinical and immunological disease and high viral load were characterized by increased C-telopeptide and particularly by markedly depressed osteocalcin levels. HIV-infected patients had enhanced activation of the TNF system. Serum concentrations of p55 and p75-TNF receptors were negatively correlated with osteocalcin, and p75-TNF receptor was positively correlated with C-telopeptide. HIV-infected patients with advanced disease also had decreased serum concentrations of 1,25-(OH)2D, but this parameter was not correlated with osteocalcin or C-telopeptide. During 24 months with highly active antiretroviral therapy there was a marked rise in serum osteolcalcin levels together with a profound fall in viral load and TNF components and a marked rise in CD4+ T cell counts. Also, there was a shift from no correlation to a significant correlation between osteocalcin and C-telopeptide levels during such therapy. The present study suggests disturbed bone formation and resorption during HIV infection. Our findings indicating synchronization of bone remodeling during highly active antiretroviral therapy may represent a previously unrecognized beneficial effect of such therapy and expand our knowledge of the interactions between cytokines and bone in the bone-remodeling process.

scholarly journals Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection

2002 ◽  
Vol 76 (3) ◽  
pp. 968-979 ◽  
Author(s):  
Simon D. W. Frost ◽  
Javier Martinez-Picado ◽  
Lidia Ruiz ◽  
Bonaventura Clotet ◽  
Andrew J. Leigh Brown
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Immune Responses ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Viral Dynamics ◽  
Viral Loads ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus

ABSTRACT Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.

scholarly journals Expansion of Viral Load Testing and the Potential Impact on Human Immunodeficiency Virus Drug Resistance

2017 ◽  
Vol 216 (suppl_9) ◽  
pp. S808-S811 ◽  
Author(s):  
Helen M Chun ◽  
Yaa F Obeng-Aduasare ◽  
Laura N Broyles ◽  
Dennis Ellenberger
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Viral Load ◽  
Load Testing ◽  
Viral Load Testing ◽  
Immunodeficiency Virus ◽  
Potential Impact
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