Viral Blips After Treatment Initiation During Acute Human Immunodeficiency Virus Infection.
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ABSTRACT:
SUBMITTER: Crowell TA
PROVIDER: S-EPMC7286371 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We analyzed human immunodeficiency virus envelope diversity in 98 acute infections. The within-host genetic diversity, divergence from transmitted/founder (T/F) strain, and the observed frequency of multiple T/F infections increased with Fiebig stage. These data identify rapid viral dynamics during acute infection with implications for clinical trials conducted in this setting.
| S-EPMC7958800 | biostudies-literature
Project description:BackgroundAlthough social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease, such as human immunodeficiency virus (HIV) [2, 3]. A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection.MethodsTo determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n = 35) and socially (n = 41) housed simian immunodeficiency virus (SIV)-infected pigtailed macaques (Macaca nemestrina).ResultsSingly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T-cell declines and more CD4 and CD8 T-cell activation compared with socially housed macaques throughout acute SIV infection.ConclusionsThese data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections.
| S-EPMC8672752 | biostudies-literature
Project description:Background:Patients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status. Methods:We conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups. Results:Among HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons. Conclusions:Regardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.
| S-EPMC5850026 | biostudies-literature
Project description:ImportanceHuman immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined.ObjectiveTo evaluate HIV treatment outcomes throughout incarceration, including jail and prison.Design, setting, and participantsRetrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data on 882 prisoners within the Connecticut Department of Correction (2005-2012) with confirmed HIV infection, who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and CD4 lymphocyte measurements, and were prescribed antiretroviral therapy.Main outcomes and measuresThree electronic databases (correctional, laboratory, and pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, <400 copies/mL) on intake and release. Secondary outcomes were mean change in log-transformed HIV-1 RNA levels and mean change in CD4 lymphocyte count during incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt of directly observed therapy, and duration of incarceration were analyzed as possible explanatory variables for HIV viral suppression in logistic regression models.ResultsAmong 882 HIV-infected prisoners with 1185 incarceration periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count increased by 98 cells/µL over time, with a higher proportion achieving viral suppression by release compared with entry (70.0% vs 29.8%; P < .001); 36.9% of antiretroviral therapy (ART) regimens were changed during incarceration. After adjusting for baseline HIV-1 RNA level, prerelease viral suppression correlated with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26-2.59) and psychiatric disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI, 1.12-1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing strategy, or directly observed therapy.Conclusions and relevanceThough just one-third of HIV-infected prisoners receiving ART entered correctional facilities with viral suppression, HIV treatment was optimized during incarceration, resulting in the majority achieving viral suppression by release. Treatment for HIV within prison is facilitated by a highly structured environment and, when combined with simple well-tolerated ART regimens, can result in viral suppression during incarceration. In the absence of important and effective community-based resources, incarceration can be an opportunity of last resort to initiate continuous ART for individual health and, following the "treatment as prevention" paradigm, potentially reduce the likelihood of HIV transmission to others after release if continuity of HIV care is sustained.
| S-EPMC4074594 | biostudies-literature
Project description:Natural hosts of simian immunodeficiency virus (SIV), such as African green monkeys (AGMs), do not progress to AIDS when infected with SIV. This is associated with an absence of a chronic type I interferon (IFN-I) signature. It is unclear how the IFN-I response is downmodulated in AGMs. We longitudinally assessed the capacity of AGM blood cells to produce IFN-I in response to SIV and herpes simplex virus (HSV) infection. Phenotypes and functions of plasmacytoid dendritic cells (pDCs) and other mononuclear blood cells were assessed by flow cytometry, and expression of viral sensors was measured by reverse transcription-PCR. pDCs displayed low BDCA-2, CD40, and HLA-DR expression levels during AGM acute SIV (SIVagm) infection. BDCA-2 was required for sensing of SIV, but not of HSV, by pDCs. In acute infection, AGM peripheral blood mononuclear cells (PBMCs) produced less IFN-I upon SIV stimulation. In the chronic phase, the production was normal, confirming that the lack of chronic inflammation is not due to a sensing defect of pDCs. In contrast to stimulation by SIV, more IFN-I was produced upon HSV stimulation of PBMCs isolated during acute infection, while the frequency of AGM pDCs producing IFN-I upon in vitro stimulation with HSV was diminished. Indeed, other cells started producing IFN-I. This increased viral sensing by non-pDCs was associated with an upregulation of Toll-like receptor 3 and IFN-?-inducible protein 16 caused by IFN-I in acute SIVagm infection. Our results suggest that, as in pathogenic SIVmac infection, SIVagm infection mobilizes bone marrow precursor pDCs. Moreover, we show that SIV infection modifies the capacity of viral sensing in cells other than pDCs, which could drive IFN-I production in specific settings.The effects of HIV/SIV infections on the capacity of plasmacytoid dendritic cells (pDCs) to produce IFN-I in vivo are still incompletely defined. As IFN-I can restrict viral replication, contribute to inflammation, and influence immune responses, alteration of this capacity could impact the viral reservoir size. We observed that even in nonpathogenic SIV infection, the frequency of pDCs capable of efficiently sensing SIV and producing IFN-I was reduced during acute infection. We discovered that, concomitantly, cells other than pDCs had increased abilities for viral sensing. Our results suggest that pDC-produced IFN-I upregulates viral sensors in bystander cells, the latter gaining the capacity to produce IFN-I. These results indicate that in certain settings, cells other than pDCs can drive IFN-I-associated inflammation in SIV infection. This has important implications for the understanding of persistent inflammation and the establishment of viral reservoirs.
| S-EPMC4301160 | biostudies-other
Project description:Understanding the properties of human immunodeficiency virus type 1 (HIV-1) variants capable of establishing infection is critical to the development of a vaccine against AIDS. Previous studies of men have shown that the HIV-1 env gene is homogeneous early in infection, leading to the suggestion that infection is established by a single transmitted variant. However, we report here that all of eight homosexual men evaluated beginning 3.7 to 9 weeks following onset of symptoms of acute infection harbored diverse virus populations in their blood, with median genetic distances averaging 1.08% in the env C2V5 region and 0.81% in the gag p17 gene. Within another 4.7 to 11 weeks, the variant lineage in env became more homogeneous, while gag sequences continued to diversify. Thus, the homogenization that has been reported to characterize acute infection is actually preceded by the replication of multiple virus variants. This early selective process focuses on viral properties within Env but not Gag p17. Hence, the viral homogeneity observed early in HIV-1 infection results from a selective process that occurs during the establishment of infection.
| S-EPMC136917 | biostudies-literature
Project description:This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH.
| S-EPMC7298306 | biostudies-literature
Project description:BackgroundEstablishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex ?4?7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection.MethodsIntegrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I-III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin ?7 (?7negative and ?7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for ?7-defined subsets at acute infection and in uninfected controls.ResultsIn Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both ?7high and ?7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, ?7high cells were enriched in integrated and total HIV-1 DNA compared to ?7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both ?7negative and ?7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in ?7high cells was correlated with their activation.Conclusions?7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.
| S-EPMC7778353 | biostudies-literature
Project description:BackgroundAntiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation.MethodsAIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing.ResultsFrom 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results.ConclusionsNovel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.Clinical trials registrationNCT02859558.
| S-EPMC8326583 | biostudies-literature
Project description:Human immunodeficiency virus type 1 is characterized by extensive genetic heterogeneity. Having previously demonstrated that, in the peripheral blood, the initial viral population is more homogeneous than at subsequent stages of infection, we have extended our studies to tissue samples, allowing comparisons between viral populations in peripheral blood and tissues during both the acute and chronic stages of infection. We found that homogeneity in gp120 sequences during the acute infection phase is not just restricted to the peripheral blood but also extends to other tissue compartments. However, in chronically infected individuals, heterogeneous and distinct viral populations were found in different compartments. We therefore conclude that the dominant and homogeneous viral population observed during the acute infection phase is likely to infiltrate lymphoid tissues and form the genetic bases for subsequent diversification. It is therefore likely that the compartmentalization of viral sequences observed in chronically infected patients reflects a gradual diversification of a common dominant viral variant rather than the preferential migration of distinct viral populations to different tissue compartments at the beginning of infection.
| S-EPMC136436 | biostudies-literature