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PubMed1997

Viral load in asymptomatic patients with CD4+ lymphocyte counts above 500 x 10(6)/l.

BACKGROUND: HIV-1-infected patients with a CD4+ lymphocyte count > or = 500 x 10(6)/l may be selected for antiretroviral treatment when viral load is above a given cut-off point. OBJECTIVES: To assess the stability of viral load measurement at CD4+ T-cell counts above 500 x 10(6)/l, and the proportion of patients selected for treatment if a cut-off point of 10,000 or 30,000 RNA copies/ml is used. DESIGN AND METHODS: Seventy-eight consecutive asymptomatic antiretroviral-naive HIV-1-infected patients with CD4+ lymphocyte counts > or = 500 x 10(6)/l, presenting for previously scheduled medical visits as outpatients, were enrolled. None of the patients had suffered from symptomatic primary infection or seroconverted within 6 months before enrollment. Two blood samples separated by a 1-month interval [day -30 (screening) and day 0 (enrollment)] were collected in an EDTA tube. Plasma was separated and frozen at -70 degrees C within 4 h of collection. HIV-1 RNA was quantified by polymerase chain reaction. CD4+ T cells were measured by flow cytometry. RESULTS: Viral load was fairly stable, and only four (13%) out of 30 pairs had a variation > or = 0.5 log10. At day -30 and day 0, log10 HIV RNA levels (mean +/- SD) were 4.24 +/- 0.7 and 4.35 +/- 0.87 log10 copies/ml plasma (P = 0.23). The difference of the mean was -0.11 (95% confidence interval, -0.28 to 0.07). At day 0 (n = 78) mean +/- SD value was 35730 +/- 73700 RNA copies/ml (range, < 200-438480; median, 9331; 25th and 75th percentiles, 1518 and 37193, respectively). In 13 patients (16%) the viral load was < 2000 copies RNA/ml. Seven out of 10 patients, who fulfilled the criteria of long-term non-progressors (LTNP), had viral load > 10,000 RNA copies/ml, and two patients had > 30,000 RNA copies/ml. Only two of the 13 patients with CD4+ T-cell counts > 750 x 10(6)/l had viral load > 10,000 copies/ml. CONCLUSIONS: A single-point viral load assessment is enough in asymptomatic patients with CD4+ lymphocytes counts > or = 500 x 10(6)/l since plasma HIV RNA measurements obtained 1 month apart are fairly stable. Approximately 25% of these patients (including some patients with LTNP criteria) will be selected for treatment if 30,000 RNA copies/ml is used as cut-off point, and approximately 50% if the cut-off point is 10,000 RNA copies/ml. Viral load > or = 10,000 is very unusual in patients with CD4+ T-cell counts > 750 x 10(6)/l.

Adult↗

PubMed2003

Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months.

OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of </= 200 HIV-RNA copies/mL. METHODS: A prospective study of one hundred and three patients was undertaken with an inclusion criteria of plasma viral load of </= 200 copies/mL. The patients had advanced HIV infection; 25% had developed AIDS. Patients were seen every 6 months for a period of 2 years. RESULTS: The median plasma viral load was < 20 copies/mL with no increase during follow-up. Thirty-one per cent had plasma viral load of </= 20 copies/mL at all visits, 44% had >/= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (IgA) differed significantly between the plasma viral load rebound groups (P < 0.05). CONCLUSION: In this cohort, selected solely on the basis of having a plasma viral load of </= 200 copies/mL, we found stable or declining viral loads in the measured compartments during 2 years of follow-up. Baseline HIV-DNA and IgA levels were higher among patients with less complete virological suppression relative to patients with persistently undetectable plasma HIV-RNA. Hence, a high cellular level of HIV-DNA and high plasma IgA may predict subsequent development of low-grade viraemia.

Adult↗

PubMed1999

Comparison of clinical manifestations of HIV infection among women by risk group, CD4+ cell count, and HIV-1 plasma viral load. HER Study Group. HIV Epidemiology Research.

OBJECTIVES: To compare the prevalence of HIV-related symptoms, physical examination findings, and hematologic variables among women whose risk for HIV is injection drug use since 1985 as opposed to sexual contact and to evaluate the influence of HIV plasma viral load and CD4+ cell count on clinical manifestations according to risk. METHODS: Participants of the HIV Epidemiology Research Study (HERS; a multicenter, prospective, controlled study of HIV infection in women) were administered a risk behavior and symptom interview, underwent a physical examination, and received hematologic testing, including CD4+ cell counts done on study entry. Plasma HIV-1 viral loads were performed on stored frozen plasma using an ultrasensitive branched-DNA (b-DNA) signal amplification assay. CD4+ counts were categorized as <200 cells/microl, 200 to 499 cells/microl, or > or =500 cells/microl, and HIV viral loads were characterized in tertiles. RESULTS: Cross-sectional analysis was conducted on data available for 724 HIV-infected women: 387 had a history of intravenous drug use and 337 were infected through heterosexual contact. The median CD4+ count was 376 cells/microl; the median HIV-1 viral load was 1135 copies/ml; and 281 of 724 HIV-infected women (38.8%) had an undetectable HIV-1 viral load. In analyses adjusting for CD4+ cell level alone and for plasma viral load combined with CD4+ cell level, injection drug users (IDUs) were more likely than those infected through heterosexual contact to report a recent episode of memory loss and weight loss, but less likely to have recent episodes of genital herpes; to have enlarged livers and a body mass index (BMI) <24, and to have hematocrit levels <34% and platelet counts <150,000 cells/ml. After adjustment for CD4+ cell level and risk group, high and medium HIV-1 plasma viral load levels were associated with the presence of oral hairy leukoplakia on examination, and only the highest level of plasma viral load was associated with recent histories of fever and thrush, oral hairy leukoplakia, pseudomembranous candidiasis, and BMI <24 on examination, and hematocrit <34%. CONCLUSIONS: In this cohort of women, the distribution of HIV-1 plasma viral load was lower than that previously reported in populations of HIV-infected men. This study also shows some differences in frequency of signs, symptoms, and laboratory values between risk groups of HIV-infected women, but these results may be due to effects of injection drug use rather than HIV infection. Signs and symptoms identified as associated with increasing levels of viral load that were not different across risk groups suggest more direct association of these findings with HIV infection.

Adult↗

PubMed2005

Undetectable viral load is associated with sexual risk taking in HIV serodiscordant gay couples in Sydney.

OBJECTIVE: To determine whether reporting that the HIV-positive partner's viral load is undetectable rather than detectable is associated with unprotected anal intercourse (UAI) in HIV serodiscordant gay couples. METHOD: A cross-sectional study nested within two cohort studies, the Health in Men (HIM) cohort of HIV-negative men, from July 2001 to December 2003 and the Positive Health (PH) cohort of HIV-positive men, from February 2002 to August 2003. The study participants were 119 men in an HIV serodiscordant regular relationship of at least 6 months duration (45 HIV-negative men from HIM, 74 HIV-positive men from PH). The main outcome measure was the occurrence of UAI within the relationship in the previous 6 months. RESULTS: Eighty-two men reported no UAI and 37 reported some UAI. Of couples in which the HIV-positive partner's viral load was reported to be undetectable, 39.4% reported UAI compared with 20.8% of those where viral load was reported to be detectable (P = 0.04). In multivariate analysis, significant predictors of UAI were younger age [odds ratio (OR), 0.94; 95% confidence interval (CI), 0.87-1.00; P = 0.05], greater HIV optimism (OR, 4.98; 95% CI, 1.25-19.8; P = 0.02) and reported undetectable viral load (OR, 2.88; 95% CI, 1.13-7.37; P = 0.03). CONCLUSIONS: Most serodiscordant gay couples do not engage in any UAI. UAI within such relationships is significantly more likely to occur where the HIV-positive partner is reported to have undetectable viral load. UAI in HIV serodiscordant relationships is problematic even if viral load is undetectable because of unknown risk parameters, viral load variability and the possibility of drug-resistant strains of HIV.

Adult↗

PubMed2005

Assessing the utility of a community pharmacy refill record as a measure of adherence and viral load response in patients infected with human immunodeficiency virus.

STUDY OBJECTIVE: To assess the utility of a community pharmacy refill record as a measure of adherence to antiretroviral agents and as a predictor of viral load response. DESIGN: Retrospective review of laboratory and community pharmacy records. SETTING: University-based human immunodeficiency virus (HIV) clinic and local community pharmacy. PATIENTS: Ninety-four patients with HIV or the acquired immunodeficiency syndrome (AIDS) who visited both settings and had retrievable pharmacy and laboratory records. MEASUREMENTS AND MAIN RESULTS: Community pharmacy records were compiled and screened for antiretroviral agent refill histories. The continuous, multiple-interval measure of medication gaps (CMG), a measure of drug nonadherence, was calculated for each antiretroviral agent. Viral load information was retrieved from the clinic records of patients who had a community pharmacy refill record documenting the previous 2 years. As refill nonadherence increased, viral load response increased, following an approximately sigmoid relationship. When the CMG score was less than 0.10, the viral load response did not change appreciably. The steepest rise in viral load response occurred with a CMG score ranging from 0.10-0.19. For values of 0.20 or greater, the viral load response was less sensitive to adherence performance. The probability (i.e., sensitivity) of having at least a 10% nonadherence record given a viral load greater than 1000 copies/ml was 80%. CONCLUSION: The community pharmacy refill record is a convenient, accessible, and useful tool for assessing adherence and predicting viral load outcomes in patients with HIV and AIDS.

Adult↗

PubMedDate not supplied

[Influenza vaccination in HIV infected children: immunologic and viral load changes].

OBJECTIVE: To identify whether influenza immunization in HIV infected children could increase HIV viral load and decrease CD4+ lymphocytes count as a consequence of the response induced by a T cell-dependent antigen. METHODS: Prospective, descriptive study, with 51 HIV infected children, vaccinated against influenza in 1999, in Florianópolis, Brazil. Blood samples were collected at three different moments: on the immunization day; between 14 and 20 days later; between 60 and 90 days later. Plasma levels of HIV viral load and CD4+ lymphocytes count were determined. Friedman ANOVA test, Student t test for dependent samples, Bonferroni correction and Wilcoxon matched test were performed for statistical analysis. RESULTS: Children's mean age was 6.08 years (1 to 12.9 years). The medians of CD4+ lymphocyte count on vaccination day and at the other two moments were 789, 645 and 768 cells/mm(3), respectively. A significant reduction was observed in the CD4+ lymphocyte count between the first and the second analyses, but the same did not happen between the first and the third analyses. There was no significant difference of CD4+ lymphocyte percentage between the first and the second analyses. The median of HIV viral load values in log10 copies/ml was 4.38, 4.30 and 4.25, at the three moments respectively. Eight out of 44 patients (18.2%) showed increase > or =0.5 log 10 copies/ml in HIV viral load between the first and the second analysis and among these, four returned to levels close to their base levels in the third analysis. CONCLUSIONS: There was no significant change in the CD4+ lymphocyte percentage, in spite of a transitory increase in HIV viral load after influenza vaccination. Caution should be used when administering vaccine against flu to children with no stable clinical and immunological conditions, mainly if they are not under effective anti-retroviral therapeutics.

CD4 Lymphocyte Count↗

PubMed1999

Cell-associated infectious HIV-1 viral load as a predictor of clinical progression and survival among HIV-1 infected injection drug users and homosexual men.

Cell-associated infectious HIV-1 viral load was measured using semi-quantitative microculture techniques to determine its predictive capability for progression to AIDS or survival among HIV-1 infected injecting drug users (IDU) and homosexual men (HM). The authors followed 296 IDU and 240 HM from February 1992 through September 1995 for: (i) death, (ii) AIDS, and (iii) AIDS or bacterial infection. At baseline, viral load was quantified using microculture techniques to determine infectious units per million peripheral blood mononuclear cells (IUPM). Data were analyzed using standard statistical methods for survival analysis. Of the 536 total participants, 106 died (20%), and 98 of the 481 AIDS-free participants developed AIDS (20%). The relative hazard of AIDS for a viral load of > or = 100 IUPM, relative to a negative culture (0 IUPM), was 6.73 (95% CI: 2.23-20.3) after adjusting for risk group, initial CD4+ count, and other covariates. The adjusted relative hazard of death for a viral load of > or = 100 IUPM vs. 0 IUPM was 2.57 (95% CI: 0.97 6.80). Viral load predicted time to death within the < 200 cells/ul CD4+ stratum. The predictive value of viral load on HIV-1 progression did not vary by risk group. These data show that cell associated infectious HIV-1 viral load was significantly predictive of progression across risk groups for AIDS and death among those severely immune compromised.

AIDS-Related Opportunistic Infections↗

PubMed2001

Association of immune complexes and plasma viral load with CD4+ cell depletion, CD8+ DR+ and CD16+ cell counts in HIV+ hemophilia patients. Implications for the immunopathogenesis of HIV-induced CD4+ lymphocyte depletion.

OBJECTIVE: There is evidence that HIV induces CD4+ depletion in part by the formation of immune complexes (IC) that attach to CD4+ blood lymphocytes. In the present study we examined the relationship of IC-coated CD4+ blood cells with retroviral replication in HAART-treated patients. PATIENTS AND METHODS: 52 hemophilia patients were studied from 1997 to 1999. Lymphocyte subsets, IgM, IgG and gp120 on CD4+ blood cells, in vitro responses of lymphocytes to mitogens, plasma neopterin and plasma viral load were measured. RESULTS: Patients with detectable viral replication and without ICs on CD4+ blood lymphocytes had a lower viral load (4100 versus 21000 HIV-1 mRNA copies/ml; P = 0.079) and higher CD4+ cell counts (310/microl versus 161/microl; P = 0.035) than patients with ICs on circulating CD4+ lymphocytes. Among patients with < 80 HIV-1 mRNA copies/ml, IC- individuals had slightly higher CD4+ lymphocyte counts than IC+ patients (384/microl versus 316/microl; n.s.). Further evidence for the clinical relevance of the ICs was obtained when 18 patients who had an undetectable viral load at previous investigations were analyzed. Among patients with a stable undetectable viral load, CD4+ counts increased in 6 of 8 IC- but in none of 2 IC+ individuals. In patients whose viral load increased during the observation period, 5 of 6 IC- but none of 2 IC+ individuals showed higher CD4+ cell counts. Impaired virus killing is suggested by lower CD16+ (35/microl versus 107/microl; P = 0.016), higher CD3+ DR+ (178/microl versus 66/microl; P = 0.006), and higher CD8+ DR+ (142/microl versus 34/microl; P = 0.017) cell counts in IC(-) patients compared to IC- patients without detectable viral load. Strong retroviral replication induced strong T cell dysfunctions. Fewer CD3+ 25+ blood lymphocytes (19/microl versus 47/microl; P = 0.006) and a lower in vitro response of T lymphocytes to the mitogens Con A (RR: 0.3 versus 1.2; P=0.023) and CD3 mab (RR: 0.5 versus 2.4; P = 0.012) was observed in IC+ patients with detectable versus undetectable viral load. CONCLUSION: Our data suggest that ICs on circulating CD4+ blood lymphocytes are primarily associated with CD4+ lymphocyte depletion whereas the plasma viral load is primarily associated with decreased T lymphocyte activation, lower CD16+ counts, and higher CD8+ DR+ lymphocytes which might be the effector cells for virus elimination.

Antigen-Antibody Complex↗

PubMed2006

Viral load and CD4 count dynamics after HIV-1 seroconversion in homosexual and bisexual men in Rio de Janeiro, Brazil.

PURPOSE: Reliable predictors of HIV disease progression are scarce in developing countries, where most HIV infections occur. We describe early virologic and immunologic events among men who have sex with men in Rio de Janeiro, Brazil. METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36 months with periodic laboratory evaluations, plasma viral load, and CD4 count assessments. Viral load and CD4 count mean trajectories were computed. For the modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720 (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was 373 cells/microL (range 260-508). Overall variation on viral loads ranged from 4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at approximately 600 days (n = 12) after estimated time of seroconversion. The initial period of HIV infection was characterized by an increase in CD4 count (n = 29) followed by a steep decline starting at approximately 200 days (508 cells, 95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those observed in developed countries, CD4 counts seem to decline at a faster rate than in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data are needed to assess the impact of interventions, such as antiretroviral therapy, on the clinical course of HIV infection in Brazil.

Adult↗

PubMed2006

Correlation of CD4 count, CD4% and HIV viral load with clinical manifestations of HIV in infected Indian children.

AIM: To correlate the absolute CD4 count, CD4% and HIV viral load with different clinical manifestations of HIV in antiretroviral-naive children. SETTING: The paediatric and perinatal HIV clinic in a tertiary care hospital over a period of 4 years, from January 1999 to December 2003. MATERIALS AND METHODS: A total of 92 highly active antiretroviral-naive, HIV-1-infected children were enrolled in a cross-sectional study. The clinical manifestations, age, sex and CDC classification of each patient were determined. CD4 count, CD4% and HIV-1 viral load were estimated at presentation and correlated with various clinical manifestations of HIV disease. RESULTS: CD4% was higher in infants (p < 0.001) and lower in children over 5 years of age (p = 0.01). Boys had a higher absolute CD4 count than girls (769 +/- 517 vs 532 +/- 430 cells/mm3, p = 0.02). Patients with lymphadenopathy (n = 43) had a high CD4 count (840 +/- 487 cells/mm3, p = 0.01) whereas patients with HIV cardiomyopathy (n = 4) had low CD4 counts (mean 182 cells/mm3, p = 0.04). In patients with failure to thrive (n = 29), the CD4% was low (14 +/- 9%, p = 0.02) and HIV-1 viral load was high (mean 4.5 x 10(5) copies/ml, p = 0.03). CD4 count, CD4% and HIV viral load did not correlate with the stage of the disease as per the CDC classification. CONCLUSION: HIV viral load, CD4 cell count and CD4% vary with age and disease complications in HIV-infected children. However, CD4 count, CD4% and viral load did not correlate with CDC classification.

AIDS-Related Opportunistic Infections↗

PubMed2005

Cerebrospinal fluid HIV viral load in different phases of HIV-associated brain disease.

We compared CSF HIV viral load in 33 asymptomatic HIV seropositive patients, 11 patients with incipient minor motor deficits (MMD), 11 patients with sustained MMD, and 16 patients with HIV-associated dementia. Patients with incipient MMD showed significantly higher CSF viral load than asymptomatic patients. Demented patients also had higher CSF viral loads than asymptomatic patients. This phenomenon is independent of antiretroviral therapy. Thus, correlation of viral load with time suggests a multiphasic course of HIV-associated CNS disease.

Adult↗

PubMed2006

Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma.

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.

Adenocarcinoma↗

PubMed2006

HIV viral load monitoring in resource-limited regions: optional or necessary?

Although it is a standard practice in high-income countries, determination of the human immunodeficiency virus (HIV) load is not recommended in developing countries because of the costs and technical constraints. As more and more countries establish capacity to provide second-line therapy, and as costs and technological constraints associated with viral load testing decrease, the question of whether determination of the viral load is necessary deserves attention. Viral load testing could increase in importance as a guide for clinical decisions on when to switch to second-line treatment and on how to optimize the duration of the first-line treatment regimen. In addition, the viral load is a particularly useful tool for monitoring adherence to treatment, performing sentinel surveillance, and diagnosing HIV infection in children aged <18 months. Rather than considering viral load data to be an unaffordable luxury, efforts should be made to ensure that viral load testing becomes affordable, simple, and easy to use in resource-limited settings.

Anti-HIV Agents↗

PubMed1999

Utility of cytomegalovirus viral load in renal transplant patients in Argentina.

BACKGROUND: Cytomegalovirus (CMV) is the most prevalent viral disease in solid organ transplantation. Detection of CMV DNA in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) frequently occurs in renal allograft recipients, yielding false positive results in seropositive patients free of CMV disease. We evaluated the clinical utility of a quantitative PCR-enzyme-linked immunosorbent assay (ELISA) for identifying patients with CMV disease. METHODS: Three hundred and fifty samples from 65 consecutive renal transplant recipients were studied. DNA was extracted from PBMC weekly up to the day of discharge and after any further admission. Samples were tested by a qualitative PCR method, and all positive samples were further studied by a quantitative PCR-ELISA method. The quantitative PCR-ELISA method used an internal standard (IS) that contained the primer sequences used in the qualitative CMV PCR. Detection and quantification was performed in 96-well plates coated with IS or CMV specific probes. RESULTS: Forty-one of 65 patients (63.1%) showed positive results by the qualitative PCR, but only 8 of these patients were diagnosed with CMV disease. Positive samples were re-analyzed by the quantitative assay. The 8 patients with CMV disease had a mean CMV viral load of 1,438+/-687 viral copies (VC)/10(6) PBMC, and the 33 without CMV disease had a mean value of 219.6+/-117.2 VC/10(6) PBMC (P<0.01). None of the 33 patients without CMV disease had viral loads higher than 500 VC/10(6) PBMC. Using 500 VC/10(6) PBMC as a cut-off value for CMV disease, the quantitative PCR showed a sensitivity and specificity of 100% compare to clinical diagnosis. CONCLUSION: CMV viral load may be useful in the diagnosis of CMV disease in renal transplant patients.

Adolescent↗

PubMed1999

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.

ADP-ribosyl Cyclase↗

PubMed1996

Relationship between viral genotype and viral load in patients with chronic hepatitis C.

To determine the distribution of hepatitis C virus (HCV) genotypes and to related genotype to viral load, genotyping and quantification of viral RNA were carried out in 35 patients with chronic hepatitis C. Subtype 1a was most prevalent (43%), followed by subtypes 1b (23%) and 3a (14%). Mean viral load (log HCV-RNA copies/ml) for subtypes 1b, 1a and 3a was 7.1 +/- 1, 5.6 +/- 1.1 and 4.1 +/- 2.4, respectively. The presence of immunoglobulin M was related to the duration of hepatitis and genotype 1 to a more severe hepatic injury and higher viral load. Differences observed in viral load for a single HCV subtype justify the need to quantify HCV-RNA prior to establishing antiviral therapy.

Analysis of Variance↗

PubMed2001

[Influenza vaccination of human immunodeficiency virus-infected patients with severe immunodepression. Impact on CD4 lymphocytes and plasma viral load].

BACKGROUND: The aim of this study was to assess the effect of influenza vaccination on plasma HIV viral load and CD4 T-lymphocytes in patients with advanced HIV disease. PATIENTS AND METHOD: Observational study carried out in HIV-infected patients with a CD4 cell count < 200 X 10(6)on highly active antiretroviral therapy(HAART). Influenza vaccine was voluntarily offered and plasma viral load and CD4 cell counts were measured at baseline, 4 weeks and 12 weeks in vaccinated and control subjects. RESULTS: Sixteen patients were analysed, 10 of them being immunized with the influenza vaccine. A significant decline in CD4 cell counts at 4 and 12 weeks and an increasing trend of viral load were seen in all immunized patients who had a high viral load at the time of vaccination (n = 6), but not in those with an undetectable viral load. The mean decrease of CD4 T-lymphocytes in these 6 patients was 49.8%. Three patients showed a huge drop of the CD4 cell count (over 60% of baseline). CONCLUSIONS: Influenza vaccination of severely immunocompromised HIV-infected patients who are failing to HAART might be associated with an immunological impairment.

Adult↗

PubMed2001

Effect of adherence to newly initiated antiretroviral therapy on plasma viral load.

OBJECTIVE: To determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads. DESIGN: Observational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA). SETTING: General Clinical Research Center at a tertiary care center. PARTICIPANTS: Forty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia. MAIN OUTCOME MEASURES: The primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads. RESULTS: Adherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84-96%], whereas detectable subjects took a median of 70% (IQR 46-93%). Adherence correlated with viral load decrease (Spearman's rho = 0.38, P < 0.01) and CD4 cell count increase (Spearman's rho = 0.25, P = 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88-98%) versus detectables, 94% (IQR 87-98%), P > 0.50]. CONCLUSIONS: Adherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important.

Adult↗