The challenge of HIV-1 genetic diversity: discordant CD4+ T-Cell count and viral load in an untreated patient infected with a subtype F strain.
Ontology highlight
ABSTRACT:
SUBMITTER: Bolivar H
PROVIDER: S-EPMC9295325 | biostudies-literature | 2009 Dec
REPOSITORIES: biostudies-literature
Publications
The challenge of HIV-1 genetic diversity: discordant CD4+ T-Cell count and viral load in an untreated patient infected with a subtype F strain.
Bolivar Hector H Geffin Rebeca R Manzi Gabriel G Fischl Margaret A MA Holzmayer Vera V Mak Wai-Bing WB Abravaya Klara K Hackett John J
Journal of acquired immune deficiency syndromes (1999) 20091201 5
Similar Datasets
Project description:To compare asymmetric dimethylarginine (ADMA) among HIV-infected and uninfected individuals and to evaluate predictors of ADMA in HIV infection.HIV-infected individuals have high rates of atherosclerosis. Endothelial dysfunction is central to atherogenesis and is one possible mechanism underlying this increased cardiovascular risk. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, higher ADMA levels predict cardiovascular events and mortality. The association between HIV infection, HIV-related factors, and ADMA has not been well described.We compared ADMA in 248 HIV-infected individuals and 50 uninfected controls. We performed multivariable analysis using traditional cardiovascular and HIV-specific factors as covariates to identify factors associated with ADMA.HIV-infected men were older, less often Caucasian, more hypertensive, and had lower HDL than uninfected men. The median duration of HIV infection was 13 years, median CD4+ count was 592 cells/?L, 76% had an undetectable viral load, and 76% were on antiretroviral therapy. ADMA levels were modestly higher in HIV-infected individuals than controls [median (IQR): 0.46 ?M (0.41-0.52) vs. 0.44 ?M (0.38-0.46), p = 0.019], but the association lost statistical significance after controlling for cardiovascular risk factors (+0.028 ?M, p = 0.054). Lower CD4+ count and both detectable and higher viral load were independently associated with increased ADMA.ADMA levels were modestly elevated in the setting of HIV infection. Notably, a greater HIV-associated inflammatory burden, as evidenced by lower CD4+ counts and higher viral loads, was associated with increased ADMA levels. Our findings suggest that HIV infection impairs endothelial function and predisposes to atherosclerosis through chronic inflammation and subsequent accumulation of ADMA.
| S-EPMC3691342 | biostudies-literature
Project description:BackgroundHCV RNA viral load is an important predictor of sustained virological response and, recently, a significant correlation with liver fibrosis was described. We investigated on possible influence of clinical and viro-immunological variables on HCV viral load in HIV-HCV co-infected patients over a study time of three years (2009-2012).MethodsWe retrospectively enrolled 98 adult patients with a diagnosis of chronic HIV infection in 2009, a diagnosis of chronic HCV infection with a detectable plasma HCV RNA in 2009 and 2012, HCV therapy-naïve or with failed and stopped antiviral treatment before June 2008. The following variables were recorded: age, gender, HCV genotype, IL28B rs12979860 CC genotype, HCV treatment status, advanced liver fibrosis diagnosis, antiretroviral therapy, CD4+ cell count, HCV viral load, HIV RNA (plasma HIV-1 RNA levels were measured from blood samples every three months at least). The correlation was established using linear regression analysis, analysis of variance and Fisher's exact test. Comparisons between groups were performed using Fisher's exact test, the independent samples t-test and the t-test for paired data, as appropriate, for continuous variables. A mixed mode (ME) maximum likelihood linear regression model was constructed to evaluate the dependence of HCV viral load.ResultsHCV RNA levels did not change significantly from 2009 to 2012 (from 3924650 ± 5320177 IU/ml to 3085128 ± 3372347 IU/ml, p = 0.13); the CD4+ count increased significantly (from a mean of 576 to a mean of 654, p = 0.003). Using linear regression, a positive correlation was observed for HCV load and genotype 1 (p = 0.002), nonresponder status (p = 0.04) and with interleukin 28B CC allele (p = 0.05). Other studied covariates failed to reach a significant correlation.ConclusionsThe HCV RNA load, a known pretreatment predictor of response to antiviral therapy, was independent of the two main parameters of HIV disease, plasma HIV RNA and CD4 cell count, over an observation time of 3 years in patients with recovered or spontaneously maintained immunocompetence.
| S-EPMC4124775 | biostudies-literature
Project description:A successful prophylactic vaccine is characterized by long-lived immunity, which is critically dependent on CD4 T cell-mediated helper signals. Indeed, most licensed vaccines induce antigen-specific CD4 T cell responses, in addition to high-affinity antibodies. However, despite the important role of CD4 T cells in vaccine design and natural infection, few studies have characterized HIV-specific CD4 T cells due to their preferential susceptibility to HIV infection. To establish at the population level the impact of HIV-specific CD4 T cells on viral control and define the specificity of HIV-specific CD4 T cell peptide targeting, we conducted a comprehensive analysis of these responses to the entire HIV proteome in 93 subjects at different stages of HIV infection. We show that HIV-specific CD4 T cell responses were detectable in 92% of individuals and that the breadth of these responses showed a significant inverse correlation with the viral load (P = 0.009, R = -0.31). In particular, CD4 T cell responses targeting Gag were robustly associated with lower levels of viremia (P = 0.0002, R = -0.45). Importantly, differences in the immunodominance profile of HIV-specific CD4 T cell responses distinguished HIV controllers from progressors. Furthermore, Gag/Env ratios were a potent marker of viral control, with a high frequency and magnitude of Gag responses and low proportion of Env responses associated with effective immune control. At the epitope level, targeting of three distinct Gag peptides was linked to spontaneous HIV control (P = 0.60 to 0.85). Inclusion of these immunogenic proteins and peptides in future HIV vaccines may act as a critical cornerstone for enhancing protective T cell responses.
| S-EPMC3255877 | biostudies-other
Project description:HIV-1-infected elite controllers or suppressors (ES) maintain undetectable viral loads (< 50 copies/mL) without antiretroviral therapy. The mechanisms of suppression are incompletely understood. Modulation of HIV-1 replication by miRNAs has been reported, but the role of small RNAs in ES is unknown. Using samples from a well-characterized ES cohort, untreated viremic patients, and uninfected controls, we explored the PBMC miRNA profile and probed the relationships of miRNA expression, CD4+ T-cell counts, and viral load.miRNA profiles, obtained using multiple acquisition, data processing, and analysis methods, distinguished ES and uninfected controls from viremic HIV-1-infected patients. For several miRNAs, however, ES and viremic patients shared similar expression patterns. Differentially expressed miRNAs included those with reported roles in HIV-1 latency (miR-29 family members, miRs -125b and -150). Others, such as miR-31 and miR-31*, had no previously reported connection with HIV-1 infection but were found here to differ significantly with uncontrolled HIV-1 replication. Correlations of miRNA expression with CD4+ T-cell count and viral load were found, and we observed that ES with low CD4+ T-cell counts had miRNA profiles more closely related to viremic patients than controls. However, expression patterns indicate that miRNA variability cannot be explained solely by CD4+ T-cell variation.The intimate involvement of miRNAs in disease processes is underscored by connections of miRNA expression with the HIV disease clinical parameters of CD4 count and plasma viral load. However, miRNA profile changes are not explained completely by these variables. Significant declines of miRs-125b and -150, among others, in both ES and viremic patients indicate the persistence of host miRNA responses or ongoing effects of infection despite viral suppression by ES. We found no negative correlations with viral load in viremic patients, not even those that have been reported to silence HIV-1 in vitro, suggesting that the effects of these miRNAs are exerted in a focused, cell-type-specific manner. Finally, the observation that some ES with low CD4 counts were consistently related to viremic patients suggests that miRNAs may serve as biomarkers for risk of disease progression even in the presence of viral suppression.
| S-EPMC3292811 | biostudies-literature
Project description:We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.
| S-EPMC2664682 | biostudies-literature
Project description:BACKGROUND:The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. RESULTS:Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. CONCLUSIONS:These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level.
| S-EPMC3487874 | biostudies-other
Project description:ObjectivesHIV-induced immunodeficiency contributes to an increased risk of non-AIDS-defining cancers (NADC). This study aims to identify the most predictive viral load (VL) or CD4 + measures of NADC risk among people with HIV (PWH).DesignExtracted from South Carolina electronic HIV reporting system, we studied adult PWH who were cancer-free at baseline and had at least 6 months of follow-up since HIV diagnosis between January 2005 and December 2020.MethodsUsing multiple proportional hazards models, risk of NADC was investigated in relation to 12 measures of VL and CD4 + cell count at three different time intervals before NADC diagnosis. The best VL/CD4 + predictor(s) and final model were determined using Akaike's information criterion.ResultsAmong 10 413 eligible PWH, 449 (4.31%) developed at least one type of NADC. After adjusting for potential confounders, the best predictors of NADC were the proportion of days with viral suppression (hazard ratio [HR]: 0.47 (>25% and ≤50% vs. 0), 95% confidence interval [CI]: [0.28, 0.79]) and proportion of days with low CD4 + cell count (AIC = 7201.35) (HR: 12.28 (>75% vs. = 0), 95% CI: [9.29, 16.23]).ConclusionsVL and CD4 + measures are strongly associated with risk of NADC. In analyses examining three time windows, proportion of days with low CD4 + cell count was the best CD4 + predictor for each time window. However, the best VL predictor varied across time windows. Thus, using the best combination of VL and CD4 + measures for a specific time window should be considered when predicting NADC risk.
| S-EPMC10538428 | biostudies-literature
Project description:BackgroundCD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression.MethodsTime-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the "msm" package in R.ResultsResults from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count.ConclusionFrom this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.
| S-EPMC6377778 | biostudies-literature
Project description:BACKGROUND:Despite the success of prevention of mother to child transmission (PMTCT) program in South Africa, the 30% HIV prevalence among women of childbearing age requires the PMTCT program to be maximally efficient to sustain gains in the prevention of vertical HIV transmission. We aimed to determine the immunologic and virologic status at entry into antenatal care (ANC) and at childbirth among HIV positive women who conceived under the CD4<500 cells/μl antiretroviral therapy (ART) eligibility threshold and universal test and treat (UTT) policies in the Gauteng province of South Africa. METHOD:We conducted a retrospective cohort study of 692 HIV positive adult (>18 years) postpartum women who gave birth between September 2016 and December 2017. Demographic, viral load (VL) and CD4 data at ANC start (3-9 months before delivery) and delivery (3 months before/after) were obtained from medical records of consenting women. We compared CD4≥500 cell/μl and viral load (VL) suppression (<400 copes/ml) rates at ANC start and delivery among women with a pre-pregnancy ART, women known HIV positive but with in-pregnancy ART and newly diagnosed women with in-pregnancy ART. Predictors of having a high CD4 and suppressed VL were assessed by log-binomial regression. RESULTS:Of the 692 participants, 394 (57.0%) had CD4 data and 326 (47.1%) had VL data. Overall women with a pre-pregnancy ART were more likely to start ANC with CD4 count≥500 cell/μl (46.3% vs 24.8%, adjusted risk ratio (aRR) = 1.9; 95% confidence interval (95% CI): 1.4-2.5), compared to newly diagnosed women. This difference was no longer apparent at the time of delivery (aRR 1.2 95% CI: 0.4-3.7). Similarly, viral suppression at delivery was higher among women with pre-pregnancy ART (87.2% vs 69.3%, aRR 1.3, 95% CI: 1.1-1.6) as compared to the newly diagnosed women. Viral suppression rate among newly diagnosed women increased substantially by the time of delivery from 43.5% to 69.3% (p = 0.001). CONCLUSION:These results show that pre-pregnancy ART improves immunologic and virologic control during pregnancy and call for renewed efforts in HIV testing, linkage to ART and viral monitoring.
| S-EPMC7018033 | biostudies-literature
Project description:BackgroundThe prognostic value of CD4 counts and RNA viral load for identifying treatment need in HIV-infected individuals depends on (a) variation within and among individuals, and (b) relative risks of clinical progression per unit CD4 or RNA difference.Methodology/principal findingsWe reviewed these measurements across (a) 30 studies, and (b) 16 cohorts of untreated seropositive adults. Median within-population interquartile ranges were 74,000 copies/mL for RNA with no significant change during the course of infection; and 330 cells/microL for CD4, with a slight proportional increase over infection. Applying measurement and physiological fluctuations observed on chronically infected patients, we estimate that 45% of population-level variation in RNA, and 25% of variation in CD4, were due to within-patient fluctuations. Comparing a patient with RNA at upper 75(th) centile with a patient at median RNA, 5-year relative risks were 1.4 (95% CI 1.2-1.7) for AIDS and 1.5 (1.3-1.9) for death, without change over the course of infection. In contrast, for a patient with CD4 count at the lower 75(th) centile, relative risks increased from 1.0 at seroconversion to maxima of 6.3 (4.4-8.9) for AIDS and 5.5 (2.7-10.1) for death by year 6, when the population median had fallen to 300 cells/microL. Below 300 cells/microL, prognostic power did not increase, due to a narrower CD4 range.ConclusionsFindings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200-350 cells/microL, without pre-treatment RNA monitoring--while not precluding earlier treatment based on clinical, socio-demographic or public health criteria.
| S-EPMC2694276 | biostudies-literature