Viral Load Dynamics Research Articles

Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts

Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

Histological Evolution of BK Virus-Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings.

Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are not available. We studied 206 biopsies (71 patients), followed 3.09 ± 1.46 years after immunosuppression reduction. The biopsy features (% immunostain for PyV large T ag + staining and inflammation ± acute rejection) were correlated with viral load dynamics and serum creatinine to define the clinicopathological status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and 50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody-mediated allograft rejection (AMR); rejection overall affected 38% of patients (>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete viral clearance (mean 28 weeks). The only predictors of graft loss were acute rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer viral clearance (p = 0.002). Presumptive and proven PyVAN had similar presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK viremia evaluation at any point with graft dysfunction and/or biopsy evaluation. This study describes the histological evolution of PyVAN and corresponding clinicopathological correlations. Although the pathological features overall reflect the viral and immunological interactions, the PyVAN course remains difficult to predict based on any single feature. Appropriate clinical management requires repeat biopsies and determination of the PyVCPS at relevant time points, for corresponding personalized immunosuppression adjustment.

Modelling Multiple Dosing with Drug Holiday in Antiretroviral Treatment on HIV-1 Infection

A within-host mathematical model to describe the dynamics of target cells and viral load in early HIV-1 infection was developed, which incorporates a combination of RTI and PI treatments by using a pharmacokinetics model. The local stability of uninfected steady state for the model was determined using an alternative threshold. The pharmacokinetics model was employed to estimate drug efficacy in multiple drug dosing. The effect of periodic drug efficacy of pharmacokinetic type on outcome of HIV-1 infection was explored under various treatment interruptions. The effectiveness of treatment interruption was determined according to the time period of the drug holidays. The results showed that long drug holidays lead to therapy failure. Under interruption of treatments combining RTI and PI therapy, effectiveness of the treatment requires a short duration of the drug holiday.

A model to estimate the probability of human immunodeficiency virus and hepatitis C infection despite negative nucleic acid testing among increased-risk organ donors.

In 2013, guidelines were released for reducing the risk of viral bloodborne pathogen transmission through organ transplantation. Eleven criteria were described that result in a donor being designated at increased infectious risk. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission risk from an increased-risk donor (IRD), despite negative nucleic acid testing (NAT), likely varies based on behavior type and timing. We developed a Monte Carlo risk model to quantify probability of HIV among IRDs. The model included NAT performance, viral load dynamics, and per-act risk of acquiring HIV by each behavior. The model also quantifies the probability of HCV among IRDs by non-medical intravenous drug use (IVDU). Highest risk is among donors with history of unprotected, receptive anal male-to-male intercourse with partner of unknown HIV status (MSM), followed by sex with an HIV-infected partner, IVDU, and sex with a commercial sex worker. With NAT screening, the estimated risk of undetected HIV remains small even at 1day following a risk behavior. The estimated risk for HCV transmission through IVDU is likewise small and decreases quicker with time owing to the faster viral growth dynamics of HCV compared with HIV. These findings may allow for improved organ allocation, utilization, and recipient informed consent.

Combination therapy of pegylated interferon and lamivudine and optimal controls for chronic hepatitis B infection

A model for combination therapy of pegylated interferon and lamivudine is presented in this paper. A critical drug efficacy in terms of the parameters of the model comprising of coupled ordinary differential equations is obtained. The dynamics of viral load is greatly impacted by the relation of the efficacies of the individual drugs vis-a-vis the critical efficacy. A control problem is formulated and solved numerically to obtain the optimal therapeutic regimen keeping in mind both biomedical goals and cost constraints.

Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa.

Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10-7, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10-6, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisition, suggesting that this region is associated with infection as well as disease progression. Our study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment. In addition, our results also indicate the possibility of using genetic markers as HIV disease progression indicators in sub-Saharan Africans to prioritize fast progressors for antiretroviral treatment.

Modeling Pharmacodynamics on HIV Latent Infection: Choice of Drugs is Key to Successful Cure via Early Therapy

Highly active antiretroviral therapy has successfully controlled HIV replication in many patients. The treatment effectiveness may depend on the pharmacodynamics of antiretroviral drugs. In this paper, we integrate several drug-related parameters into an HIV infection model to investigate the effects of drug pharmacodynamics on the HIV latent reservoir and viral load dynamics. We showed that pharmacodynamic characteristics of drugs and the dosing schedule can significantly affect the outcome of either early or late treatment. Variations in each of the four studied parameters (the slope of the dose-response curve, the ratio of the maximum dosage to the 50% inhibitory concentration, the drug's half-life, and the dosing interval) can generate either an infection-free steady state or persistent infection when the other parameters remain unchanged. The global stability of the infection-free steady state and the viral persistence are shown to be governed by a viral invasion threshold that depends on the drug ph...

Influence of raltegravir intensification on viral load and 2-LTR dynamics in HIV patients on suppressive antiretroviral therapy

Antiretroviral therapy can suppress HIV-1 plasma viral load to below the detection limit but cannot eradicate the virus. Whether residual ongoing viral replication persists during suppressive therapy remains unclear. A few clinical studies showed that treatment intensification with an additional drug led to a lower viral load or an increase in 2-LTR (long terminal repeat), a marker for ongoing viral replication. However, some other studies found no change in the viral load and 2-LTR. In this paper, we developed multi-stage models to evaluate the influence of treatment intensification with the integrase inhibitor raltegravir on viral load and 2-LTR dynamics in HIV patients under suppressive therapy. We analyzed one model and obtained the local and global stability of the steady states. The model and its variation predict that raltegravir intensification induces a very minor decrease in the viral load and a minor increase in 2-LTR. We also compared modeling prediction with the 2-LTR data in a raltegravir intensification study. To achieve the 2-LTR increase observed in some patients, the level of viral replication needs to be substantially high, which is inconsistent with the sustained viral suppression in patients during treatment intensification. These modeling results, together with the theoretical estimate of the upper bound of the 2-LTR increase, suggest that treatment intensification with raltegravir has a minor effect on the plasma viremia and 2-LTR in patients under suppressive therapy. Other treatment strategies have to be developed for the cure or functional control of the infection.

Drivers of Inter-individual Variation in Dengue Viral Load Dynamics.

Dengue is a vector-borne viral disease of humans that endemically circulates in many tropical and subtropical regions worldwide. Infection with dengue can result in a range of disease outcomes. A considerable amount of research has sought to improve our understanding of this variation in disease outcomes and to identify predictors of severe disease. Contributing to this research, patterns of viral load in dengue infected patients have been quantified, with analyses indicating that peak viral load levels, rates of viral load decline, and time to peak viremia are useful predictors of severe disease. Here, we take a complementary approach to understanding patterns of clinical manifestation and inter-individual variation in viral load dynamics. Specifically, we statistically fit mathematical within-host models of dengue to individual-level viral load data to test virological and immunological hypotheses explaining inter-individual variation in dengue viral load. We choose between alternative models using model selection criteria to determine which hypotheses are best supported by the data. We first show that the cellular immune response plays an important role in regulating viral load in secondary dengue infections. We then provide statistical support for the process of antibody-dependent enhancement (but not original antigenic sin) in the development of severe disease in secondary dengue infections. Finally, we show statistical support for serotype-specific differences in viral infectivity rates, with infectivity rates of dengue serotypes 2 and 3 exceeding those of serotype 1. These results contribute to our understanding of dengue viral load patterns and their relationship to the development of severe dengue disease. They further have implications for understanding how dengue transmissibility may depend on the immune status of infected individuals and the identity of the infecting serotype.

Compartmentalized dynamics of cytomegalovirus replication in treated congenital infection

BackgroundCytomegalovirus (CMV) is the most prevalent congenital infection in developed countries. A significant number of infected infants develop long-term neurodevelopmental and hearing impairment irrespective of whether disease is detectable at birth. Studies of viral load and replication dynamics have informed the treatment of CMV in adult populations but no similar data exist in neonates. ObjectivesTo study CMV virus kinetics in different body fluids of babies treated for congenital infection. Study designCMV virus load was sequentially analyzed in blood, urine and saliva in 17 babies treated for symptomatic congenital CMV infection. ResultsVirus was detectable in the urine and saliva of all babies at baseline but in only 15/17 in blood. At the end of 6 weeks of antiviral treatment CMV remained detectable in 9/14 blood samples, 9/12 urine samples and 4/7 salivary swabs. Median half-life (T1/2) of virus decline in blood was 2.4 days (IQR 1.9–3.3) and basic reproductive number (Ro) was 2.3. Although T1/2 values were similar in urine and saliva to those observed in blood, virus dynamics differed both during and after treatment. ConclusionsT1/2 and Ro in blood in this group of neonates were similar to values derived from studies of immunocompromised adults. The persistent viremia observed in treated neonates cannot therefore be adequately explained by the virus dynamics early in treatment. The different dynamics exhibited in blood and urine suggests that studying changes in distinct body compartments may assist in further understanding long-term manifestations of disease.

Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection.

Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5α restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4(+) T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel "bar-coded" challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. Nonhuman primate research has relied on only a few infectious molecular clones for a myriad of diverse research projects, including pathogenesis, preclinical vaccine evaluations, transmission, and host-versus-pathogen interactions. With new data suggesting a selected phenotype of the virus that causes infection (i.e., the transmitted/founder virus), we sought to generate and characterize infectious molecular clones from two widely used simian immunodeficiency virus lineages (SIVmac251 and SIVsmE660). Although the exact requirements necessary to be a T/F virus are not yet fully understood, we generated cloned viruses with all the necessary characteristic of a successful T/F virus. The cloned viruses revealed typical acute and set point viral-load dynamics with pathological immune activation, lymphoid tissue damage progressing to significant immunodeficiency, and AIDS-defining clinical endpoints in some animals. These T/F clones represent a new molecular platform for studies requiring authentic T/F viruses.

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

Modelling the Innate Immune Response against Avian Influenza Virus in Chicken.

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -β and -γ, lung (i.e. pulmonary) cells and Natural Killer cells. We use recent results from experimentally infected chickens to validate some of the model predictions. The model includes an initial exponential increase of the viral load, which we show to be consistent with experimental data. Using this exponential growth model we show that the duration until a given viral load is reached in experiments with different inoculation doses is consistent with a model assuming a linear relationship between initial viral load and inoculation dose. Subsequent to the exponential-growth phase, the model results show a decline in viral load caused by both target-cell limitation as well as the innate immune response. The model results suggest that the temporal viral load pattern in the lungs displayed in experimental data cannot be explained by target-cell limitation alone. For biologically plausible parameter values the model is able to qualitatively match to data on viral load in chicken lungs up until approximately 4 days post infection. Comparison of model predictions with data on CD107-mediated degranulation of Natural Killer cells yields some discrepancy also for earlier days post infection.

The dynamics of HCV DNA and HBsAg levels in acute hepatitis B patients in monoinfection and coinfection of other hepatitis viruses

Introduction Changes in the levels of DNA of hepatitis B virus (HBV) infection and the quantitative content of the surface antigen (HBsAg) in acute hepatitis B, as well as the concomitant co-injection of other hepatitis viruses have been insufficiently studied so far. Materials and Methods In 21 patients with acute HBV monoinfection and 27 patients with co-infection of HBV + HCV and/ or HDV three to four serum samples were withdrawn with interval of 6-10 days and the dynamics of HBV viral load and concentration of HBsAg was examined. Results Logarithm of the concentration of DNA HBV was established to decrease from 4.0 ± 0.65 to 3.0 ± 0.59, to 2.5 ± 0.47, to 1.9 ± 0.65 (IU /ml, M ± s), the half-life of DNA HBV was increased from 1.6 days at baseline to 4 days to the end of the study. The decline of the HBsA concentration proceeded much slower: from 38 to 23, 12, 3.8 pg/ml. Half-life period of HBsAg accounted of 8 days at the beginning and 5.7 days at the end of the study, however, in 11 patients there was observed rapid elimination of HBsAg and disappearance of HBV DNA. Conclusion The fact of co-infection with hepatitis C virus (HCV) had no significant effect on the dynamics of HBV DNA and HBsAg levels. In patients infected with Hepatitis D virus (HDV) HBV viral load was significantly lower, and the concentration of HBsAg, by contrast, is significantly higher than in acute monoinfection with HBV. Thus, in acute hepatitis B DNA elimination occurs much faster than the elimination of HBsAg. In addition, in co-infection HDV inhibits replication of HBV, but at the same time stimulates the expression of HBsAg. The obtained data should be considered in the interpretation of laboratory tests in patients with acute hepatitis B, both in the earlier period, and at follow-up.

The Impact of Alcohol use during Seemingly Suppressive Antiretroviral Therapy: Risk of Blips and Rebounds

Background: After achieving “clinically undetectable levels”, many HIV positive individuals remain in a phase called residual viremia. Some of these patients have viral blips, while others have viral rebounds, but little is known about their causes. Our objective was to identify the rate and determinants of viral load dynamics, particularly the effect of hazardous alcohol use. Methods: We evaluated 400 cohort participants starting ART and comprehensively assessed alcohol intakes using validated instruments. Viral load (VL) was measured at four time points (baseline, 6 12 and 18 months), along with potential covariates, such as demographics, CD4, CD8, platelets, alcohol use profiles, and medication adherence. VL suppression was assessed at 6 months and then based on prior published work, viral trajectories were censored according to the following categories: reference Group 1 (very low viremia<50), viral blips Group 2 (50-399), and the viral rebound Group 3 (400-1000 copies/mL). Factors associated with VLV, blips, and rebounds were identified using logistic regression models. Results: Among the 320 subjects who achieved undetectable viral loads, during the subsequent 12 months of therapy, 20% exhibited viral blips, and 43% had viral rebounds. Despite similar medication adherence (95% vs. 85%), hazardous alcohol users were twice more likely to have a viral rebound, compared with non-users (95% CI, 1.8-2.5; p=0. 000). Alcohol users were also more likely to have blips. After adjustment for potential confounders, regression analyses indicated that CD4 counts at the time of therapy initiation, alcohol use, and age were independently associated with blips and rebounds. Conclusions: In this cohort, hazardous alcohol use was associated with an increased risk of viral blips, and thus will likely play an important role in the development of effective strategies to eliminate HIV, and prevent transmission and disease progression. These findings have implications for clinicians, researchers and policy makers, as they highlight the detrimental effects of alcohol use while on ART therapy.

Vaccination of pigs reduces Torque teno sus virus viremia during natural infection

Anelloviruses are a group of single-stranded circular DNA viruses infecting several vertebrate species. Four species have been found to infect swine, namely Torque teno sus virus (TTSuV) 1a and 1b (TTSuV1a, TTSuV1b; genus Iotatorquevirus), TTSuVk2a and TTSuVk2b (genus Kappatorquevirus). TTSuV infection in pigs is distributed worldwide, and is characterized by a persistent viremia. However, the real impact, if any, on the pig health is still under debate. In the present study, the impact of pig immunization on TTSuVk2a loads was evaluated. For this, three-week old conventional pigs were primed with DNA vaccines encoding the ORF2 gene and the ORF1-A, ORF1-B, and ORF1-C splicing variants and boosted with purified ORF1-A and ORF2 Escherichia coli proteins, while another group served as unvaccinated control animals, and the viral load dynamics during natural infection was observed. Immunization led to delayed onset of TTSuVk2a infection and at the end of the study when the animals were 15 weeks of age, a number of animals in the immunized group had cleared the TTSuVk2a viremia, which was not the case in the control group. This study demonstrated for the first time that TTSuV viremia can be controlled by a combined DNA and protein immunization, especially apparent two weeks after the first DNA immunization before seroconversion was observed. Further studies are needed to understand the mechanisms behind this and its impact for pig producers.

Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients.

Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world’s population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime® m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. Results: The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p < 0.001). Additionally, the viral load was found to vary when tested before and after hemodialysis (p < 0.001). Conclusion: The prevalence of HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the dialyzer membrane.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0238-z) contains supplementary material, which is available to authorized users.

Dynamics of CD4 Lymphocytes and Viral Load at the Natural History of Perinatal HIV-infection

This article presents the analysis of indicators of CD4 lymphocyte count and viral load in the natural history (in the absence of ART) in perinatally HIV-infected children. It was revealed that perinatal way of transmission is characterized by a higher rate of immunodeficiency progression. It may be associated with intrauterine infection, as well as an early defeat HIV immature immune system of the child. The concentration of virus in perinatally infected children since the beginning of the observation and in 30 months after infection is more than in parenterally infected children in 5 and 2 times, respectively, which determines a infavourable version of the disease in perinatally infected children.

Estimation and assessment of markov multistate models with intermittent observations on individuals.

Multistate models provide important methods of analysis for many life history processes, and this is an area where John Klein made numerous contributions. When individuals in a study group are observed continuously so that all transitions between states, and their times, are known, estimation and model checking is fairly straightforward. However, individuals in many studies are observed intermittently, and only the states occupied at the observation times are known. We review methods of estimation and assessment for Markov models in this situation. Numerical studies that show the effects of inter-observation times are provided, and new methods for assessing fit are given. An illustration involving viral load dynamics for HIV-positive persons is presented.

ASSOCIATION BEETWEEN IL-28β POLYMORPHISMS AND EFFECTIVENESS OF CONCOMITANT THERAPY OF HIV INFECTION IN PATIENTS WITH HCV/HIV CO-INFECTION DURING THE ANTIVIRAL THERAPY

Abstract. The aim of the study was to evaluate the associations between the polymorphism rs8099917 IL-28β and changing of HIV viral load and the effectiveness of high active antiretroviral therapy during the treatment of chronic hepatitis C in HIV-infected patients. 80 HIV/HCV-infected patients were recruited in the study. Antiviral therapy was performed with pegylated interferon-α and ribavirin combined with concomitant HIV therapy. Polymerase chain method was used for the gene polymorphism IL 28b (rs8099917) and HIV viral load estimation. More than half (56.25%) patients treated with combined therapy showed a significant decrease in CD4 T-lymphocytes in TG- and TT-genotype groups. Furthermore, viral load of HIV RNA significantly declined in the group with TT genotype during the treatment. It was concluded that rs8099917 polymorphism of the gene IL-28β affects the dynamics of the HIV RNA viral load in HIV-infected patients receiving concomitant therapy for treatment of viral hepatitis C. Herewith, rs8099917 polymorphism combined with other factors can be used as a predictor of high active antiretroviral therapy effectiveness.