Markers Of Human Immunodeficiency Virus Disease Progression Research Articles

Surrogate Biomarkers of Disease Progression in Human Pegivirus Seropositive Human Immunodeficiency Virus-Infected Individuals.

Scientific observations indicate that an actively prevailing systemic condition could alleviate the pathology of another disease. Human pegivirus (HPgV), a highly ubiquitous flavivirus is believed to be associated with slow human immunodeficiency virus (HIV) disease progression, and has seldom been linked to hepatic pathology. In this study, we investigated whether HPgV seropositivity had any impact on surrogate markers of HIV disease progression in a cohort of HIV-infected HPgV seropositive (n = 28) and seronegative (n = 12) individuals who were prospectively evaluated for absolute CD4+ T cell counts, plasma viral load (PVL), liver enzymes, and plasma cytokine levels. The HIV PVL was relatively lower in HPgV seropositive than in HPgV seronegative HIV-infected subjects. Clinical markers of hepatic injury were significantly low among HPgV seropositive HIV-infected participants. HPgV seropositive individuals showed significantly higher levels of interleukin-7 (IL-7), and although not significant, the levels of IL-6 were lower among HPgV seropositive subjects. Spearman correlation analysis showed that the absolute CD4+T cell count was inversely correlated with HIV PVL. Exposure to HPgV appears to have a positive prognostic impact on the levels of surrogate biomarkers of HIV disease progression.

Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls.

BackgroundCytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.MethodsA total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured.ResultsCMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population.ConclusionsCMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.

2108 CD4 Levels and Viral Load During Ulcerative Colitis Flares in Patients With HIV: A Case Series

INTRODUCTION: Accumulating evidence indicates an association between CD4 count and Ulcerative colitis (UC) flares in patients with Human Immunodeficiency Virus (HIV)[1,4], whereby patients who have low CD4 counts are less likely to experience UC flares compared to those who have normal CD4 counts. While the exact mechanism is unknown, it is hypothesized that an immunosuppressed state allows for the remission of UC; this idea has been deemed the “Remission Hypothesis” [1]. CASE DESCRIPTION/METHODS: Objective: To present a case series of 3 patients with concomitant HIV and Ulcerative Colitis (UC) and examine the association between UC flares, CD4 counts and viral load over time. METHODS: Patient records at two urban university-affiliated medical centers were queried for patients with concomitant HIV and UC. ICD 9 and ICD 10 diagnostic codes for HIV and UC were used to identify patients. Inclusion criteria were confirmed UC via endoscopy, outpatient follow up, viral load and CD4 count documentation. CD4 counts and viral loads levels were compared during hospitalizations and outpatient follow-ups. RESULTS: 7 patients with UC and HIV were identified; 3 of these 7 patients had sufficient data available for further analysis. Our three patients lived with HIV for an average of 10 years. Patient 1 experienced 4 UC flares requiring inpatient hospitalizations while maintaining CD4 counts above 250 cells/µL and undetectable viral loads (Table 1). Patient 2 had five UC flares with CD4 counts above 250 cells/µL; an undetectable viral load was noted during 4 of the UC flares (Table 2). Patient 1 had two flares with CD4 counts above 250 cells/µL; the viral load was undetectable during flares (Table 3). DISCUSSION: The remission hypothesis suggests that patients who have concomitant HIV and UC can experience remission of their inflammatory bowel disease as their CD4 count declines [1]. HIV viral load is a more accurate and more important marker of HIV disease progression, and therefore, a relationship between viral load and UC flares need to be further studied. Our patients continued to experience flares despite suppressed viral load, and CD4 counts above 250 cells/µL. This case series is the first study that considers viral load and CD4 counts when considering IBD flares and disease progression. These findings raise the question of whether IBD flares occurs as a consequence of CD4 count above 250 or low viral load. Further studies with larger populations are needed to elucidate the pathophysiology of IBD and HIV coexistence.

Correlation of High Interleukin 17A and Interleukin 6 Levels with High Virus Load Among Subtype C HIV-infected, Antiretroviral Therapy-naive Zimbabwean Patients: A Cross-sectional Study

Introduction:In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression. We quantified Th1/Th2/Th17 cytokines in an antiretroviral therapy naïve (ART) cohort to investigate their correlation with traditional markers of HIV disease progression; CD4+ T-lymphocytes and virus load (VL).Methods:We enrolled 247 HIV-infected ART-naïve participants into the study. CD4+ T- and CD8+ T-lymphocytes were enumerated using flow cytometry. VL was quantified using the Cavidi ExaVirTMLoad assay. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were quantified using the BD Cytometric Bead Array Human Th1/Th2/Th17 cytokine assay. The Kendall’s rank correlation coefficient was used to determine the correlation between log10transformed data for cytokine levels and CD4+ T- and CD8+ T-lymphocytes, CD4/CD8 ratio, and VL.Results:The median CD4+ T- and CD8+ T-lymphocyte counts were 458 cells/µL (IQR:405-556) and 776 cells/µL (IQR:581-1064), respectively. The median CD4/CD8 ratio was 0.6 (IQR: 0.45-0.86). The median VL was log103.3.copies/mL (IQR:2.74-3.93). Low CD4+ T-lymphocyte counts (p=0.010) and CD4/CD8 ratio (p=0.044) were significantly correlated with high VL. There was no significant correlation of cytokine levels with CD4+ T-, CD8+ T-lymphocyte counts and CD4/CD8 ratio. However, high levels of IL-17A (p=0.012) and IL-6 (p=0.034) were significantly correlated with high VL.Conclusion:Our study contributes to the little knowledge available on the role of cytokine profiles in the immune response to subtype C HIV infection.

Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection.

Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH. Cross-sectional and longitudinal assessments of plasma βDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and βDG-specific receptor expression on monocytes and natural killer (NK) cells. Plasma βDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). βDG increased over 24 months without ART but remained unchanged after 24 months of treatment. βDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid-binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated βDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively. PLWH have elevated plasma βDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further βDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-acquired immunodeficiency syndrome events.

Antihelminthics in helminth-endemic areas: effects on HIV disease progression.

BackgroundHelminth infections, such as soil‐transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis, are prevalent in many countries where human immunodeficiency virus (HIV) infection is also common. There is some evidence from observational studies that HIV and helminth co‐infection may be associated with higher viral load and lower CD4+ cell counts. Treatment of helminth infections with antihelminthics (deworming drugs) may have benefits for people living with HIV beyond simply clearance of worm infections.This is an update of a Cochrane Review published in 2009 and we have expanded it to include outcomes of anaemia and adverse events.ObjectivesTo evaluate the effects of deworming drugs (antihelminthic therapy) on markers of HIV disease progression, anaemia, and adverse events in children and adults.Search methodsIn this review update, we searched online for published and unpublished studies in the Cochrane Library, MEDLINE, EMBASE, CENTRAL, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICRTP), ClinicalTrials.gov, and the WHO Global Health Library up to 29 September 2015. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted the authors of included studies.Selection criteriaWe searched for randomized controlled trials (RCTs) that compared antihelminthic drugs with placebo or no intervention in HIV‐positive people.Data collection and analysisTwo review authors independently extracted data and assessed trials for eligibility and risk of bias. The primary outcomes were changes in HIV viral load and CD4+ cell count, and secondary outcomes were anaemia, iron deficiency, adverse events, and mortality events. We compared the effects of deworming using mean differences, risk ratios (RR), and 95% confidence intervals (CIs). We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Main resultsEight trials met the inclusion criteria of this review, enrolling a total of 1612 participants. Three trials evaluated the effect of providing antihelminthics to all adults with HIV without knowledge of their helminth infection status, and five trials evaluated the effects of providing deworming drugs to HIV‐positive individuals with confirmed helminth infections. Seven trials were conducted in sub‐Saharan Africa and one in Thailand.Antihelminthics for people with unknown helminth infection statusProviding antihelminthics (albendazole and praziquantel together or separately) to HIV‐positive adults with unknown helminth infection status may have a small suppressive effect on mean viral load at six weeks but the 95% CI includes the possibility of no effect (difference in mean change −0.14 log10 viral RNA/mL, 95% CI −0.35 to 0.07, P = 0.19; one trial, 166 participants, low quality evidence).Repeated dosing with deworming drugs over two years (albendazole every three months plus annual praziquantel), probably has little or no effect on mean viral load (difference in mean change 0.01 log10 viral RNA, 95% CI: −0.03 to −0.05; one trial, 917 participants, moderate quality evidence), and little or no effect on mean CD4+ count (difference in mean change 2.60 CD4+ cells/µL, 95% CI −10.15 to 15.35; P = 0.7; one trial, 917 participants, low quality evidence).Antihelminthics for people with confirmed helminth infectionsTreating confirmed helminth infections in HIV‐positive adults may have a small suppressive effect on mean viral load at six to 12 weeks following deworming (difference in mean change −0.13 log10 viral RNA, 95% CI −0.26 to −0.00; P = 0.04; four trials, 445 participants, low quality evidence). However, this finding is strongly influenced by a single study of praziquantel treatment for schistosomiasis. There may also be a small favourable effect on mean CD4+ cell count at 12 weeks after deworming in HIV‐positive populations with confirmed helminth infections (difference in mean change 37.86 CD4+ cells/µL, 95% CI 7.36 to 68.35; P = 0.01; three trials, 358 participants, low quality evidence).Adverse events and mortalityThere is no indication that antihelminthic drugs impart additional risks in HIV‐positive populations. However, adverse events were not well reported (very low quality evidence) and trials were underpowered to evaluate effects on mortality (low quality evidence).Authors' conclusionsThere is low quality evidence that treating confirmed helminth infections in HIV‐positive adults may have small, short‐term favourable effects on markers of HIV disease progression. Further studies are required to confirm this finding. Current evidence suggests that deworming with antihelminthics is not harmful, and this is reassuring for the routine treatment of confirmed or suspected helminth infections in people living with HIV in co‐endemic areas.Further long‐term studies are required to make confident conclusions regarding the impact of presumptively deworming all HIV‐positive individuals irrespective of helminth infection status, as the only long‐term trial to date did not demonstrate an effect.11 April 2019No update plannedResearch area no longer activeThis is no longer a current research question. All eligible published studies found in the last search (29 Sep, 2015) were included

Treatment of W. bancrofti (Wb) in HIV/Wb coinfections in South India.

BackgroundThe disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections.Methodology/Principal FindingsTo assess the influence of pre-existing Wuchereria bancrofti infection on HIV progression, we performed a case-controlled treatment study of HIV positive individuals with (FIL+) or without (FIL-) W. bancrofti infection. Twenty-eight HIV+/FIL+ and 51 matched HIV+/FIL- subjects were treated with a single dose of diethylcarbamazine and albendazole (DEC/Alb) and followed for a year at regular intervals. Sixteen of the HIV+/FIL+ subjects (54%) and 28 of the HIV+/FIL- controls (57%) were on antiretroviral therapy (ART) during the study. Following treatment, no differences were noted in clinical outcomes between the 2 groups. There also was no significant difference between the groups in the HIV viral load at 12 months as a percentage of baseline viral load (HIV+/FIL+ group had on average 0.97 times the response of the HIV+/FIL- group, 95% CI 0.88, 1.07) between the groups. Furthermore, there were no significant differences found in either the change in viral load at 1, 3, or 6 months or in the change in CD4 count at 3, 6, or 12 months between the 2 groups.Conclusions/SignificanceWe were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas.Trial RegistrationClinicalTrials.gov NCT00344279

Diffusion tensor MRI evaluation of the corona radiata, cingulate gyri, and corpus callosum in HIV patients

To evaluate the white matter integrity of the corona radiata, cingulate gyri, and corpus callosum in patients with human immunodeficiency virus (HIV) infection through diffusion tensor imaging (DTI). Thirty-four patients with at least 5 years of HIV infection and 27 healthy controls underwent magnetic resonance imaging (MRI) in a 1.5 T scanner. A voxelwise-based technique was used to analyze the DTI data. We found that in the body of corpus callosum the fractional anisotropy (FA) was significantly reduced, whereas mean diffusivity (MD) and radial diffusivity (RD) were increased in HIV patients. Analyzing the corona radiata, axial diffusivity (AD) and MD were significantly increased in the left superior region, MD and RD were increased in the left posterior area, and, furthermore, MD was also increased in the right posterior region. No significant abnormalities were found on the cingulate gyri. The white matter damage, related to FA reduction, was associated with increased RD, indicating that demyelization might be the pathophysiological result of this damage. Since the DTI can detect abnormalities in the normal-appearing white matter, this technique may play a role as an early marker of HIV disease progression, including clinical manifestations such as cognitive impairment.

Human Immunodeficiency Virus (HIV) types Western blot (WB) band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare, Zimbabwe

BackgroundExpensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression.MethodsHIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV gag antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy.ResultsAmong the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7%) had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants.ConclusionAbsence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease diagnosis, WB test could also be used in conjunction with simpler tests like full blood counts and patient clinical assessment as a relatively cheaper disease monitoring tool required prior to accessing antiretroviral therapy for poor resource settings. However, there is also need to factor in the role of host-parasite genetics and interactions in disease progression.

Usefulness of hemoglobin and albumin as prognostic markers for highly active antiretroviral therapy for HIV-1 infection

Usefulness of hemoglobin and albumin as prognostic markers for highly active anti-retroviral therapy for HIV-1 infection. Anemia and hypoalbuminemia are common complications in human immunodeficiency virus (HIV) infection. We aimed to investigate the changes in hemoglobin and albumin levels in response to highly active antiretroviral therapy (HAART). Further, we evaluated the appropriateness of using hemoglobin and albumin as HIV disease progression markers. A prospective longitudinal study of 122 subjects was carried out. Pre-treatment, one year, and two year post-treatment hemoglobin, and albumin levels were correlated with respective CD4+ T cell counts. The sensitivity, specificity, and positive predictive value of each marker against CD4+ T cell counts were calculated in order to establish the appropriateness of use of these parameters as surrogate disease progression and prognostic markers. Mean hemoglobin and albumin levels pre-, one, and two year post HAART were 9.7 g/dL, 12.1 g/dL, and 13.1 g/dL, respectively, P = 0.001; albumin: 3.7 gm%, 4.4 gm%, and 4.7 gm%, respectively, P = 0.001. There was a positive correlation between hemoglobin, albumin, and CD4+ T cell count at pre-treatment, one year, and two year post-treatment visit. Both albumin and hemoglobin had high sensitivity when compared to CD4+ T cell counts. Hemoglobin and albumin levels were found to increase after initiation of HAART. Hemoglobin and albumin were seen to be a strong prognostic marker of HIV disease progression at pre-, one, and two year post-treatment. Therefore, hemoglobin and albumin may be used together along with CD4 + T cell counts in HIV management, particularly in resource-poor settings.

Infection: Is it a cause of bladder cancer?

This article reviews the literature regarding the possible correlation between infection and occurrence of bladder cancer. The PubMed literature database was searched from inception to January 2008. Keywords of bladder, cancer, parasitic, bacterial, viral and infection, were used. Forty studies were included in the review. Several investigators support the idea that schistosomiasis is aetiologically related to the development of bladder cancer in individuals infected with Schistosoma haematobium. Approximately 70% of those with chronic schistosomiasis who have bladder cancer develop squamous cell rather than transitional cell carcinoma. Several investigators suggest that bacteria may play a role in inducing bladder cancer. Clinically, researchers have linked the development of infection, urinary stones and indwelling catheters with bladder cancer. Nevertheless, to date, no prospective study has examined the association between urinary tract infection and bladder cancer risk. The possibility that infection by human papilloma virus (HPV) is a risk factor contributing to bladder cancer has been investigated but no definite conclusions have been drawn. Thus, the debate remains open as to whether there is any direct link between chronic HPV infection and bladder cancer. Only 15 cases of vesical carcinoma have been reported, to date, in the setting of human immunodeficiency virus (HIV). The rare occurrence of bladder cancer during HIV infection and the lack of correlation with the laboratory markers of HIV disease progression may suggest a trivial association between two unrelated disorders. BK virus is oncogenic in newborn hamsters and can transfer to mammalian cells in vitro, but there is little consistent evidence of a link with human bladder cancer. Studies showed no correlation between herpes simplex virus (HSV) and bladder cancer, but bladder cancer becomes infected with HSV much more easily than non-neoplastic urothelium. In conclusion, with the exception of chronic infection with S. haematobium, the association between the occurrence of bladder cancer and chronic bacterial or viral infections could not be confirmed. Prospective studies with large numbers of patients and controls are required to confirm this issue.

Impact of Hepatitis C on HIV Progression in Adults With Alcohol Problems

Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference -46.0 cells/microL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population.

Memory Implications of a “Fornix White Line” in HIV Infection

The "fornix white line" (FWL) is a brain abnormality detected on magnetic resonance imaging (MRI) in some people with human immunodeficiency virus (HIV) infection. This finding has previously been associated with clinical findings of cognitive disturbance, particularly regarding memory. The current study provides preliminary substantiation of the previously reported clinical finding of FWL-associated memory disturbance through formal psychometric evaluation over time. Specifically, despite comparable baseline performances, 8-10 months later subjects without the FWL improved performance on neuropsychological verbal memory testing, while subjects with the FWL declined; the magnitude of this dissociation on follow-up was 1.5 to 2.2 standard deviations. In contrast, general cognitive status, as assessed through performance on the Mini-Mental State Exam, remained comparable between groups and stable over time. Further, the comparable CD4 count and Karnofsky scores at baseline counters the argument that the FWL is simply a marker of HIV disease progression. These preliminary findings suggest the need for future research of the hypotheses raised thereby; particularly salient is the hypothesis that the FWL may serve as an earlier marker indicating anti-CMV treatment before memory impairment is clinically apparent.

New Studies Say Viral Burden Tops CD4 as a Marker of HIV Disease Progression

EARLY FINDINGS from two large clinical studies may signal a major shift in how physicians monitor disease progression and use antiviral drugs in patients infected with the human immunodeficiency virus (HIV). The data indicate that a change in viral burden, as measured by RNA polymerase chain reaction (RNA-PCR) at baseline and following therapy, is superior to CD4 cell count as a surrogate marker of HIV disease progression. "This is the first large-scale trial supporting this finding," said William W. Freimuth, MD, PhD, medical monitor of the studies sponsored by Pharmacia & Upjohn Inc, Kalamazoo, Mich. Most clinicians and activists already consider viral burden testing useful, as a result of findings from smaller studies, Freimuth noted. "Now these data give it ammunition." The findings, as yet unpublished, are "very important," said John Phair, MD, director of the Comprehensive AIDS Center at Northwestern University Medical School, Chicago, Ill, and an investigator at

Coinfection with human T-cell lymphotropic virus type I and HIV in Brazil. Impact on markers of HIV disease progression

<h3>Objectives.</h3> —To study the effect of human T-cell lymphtropic virus type I (HTLV-I) on markers of human immunodeficiency virus (HIV) disease progression. <h3>Design.</h3> —A retrospective, nested case-control study. <h3>Setting.</h3> —A university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. <h3>Participants.</h3> —Human immunodeficiency virus—seropositive adults participating in a prospective HIV cohort study. <h3>Main Outcome Measures.</h3> —The HIV clinical stage, CD4⁺lymphocyte counts, and other laboratory parameters in 27 individuals infected with HIV and HTLV-I (coinfection) and 99 age-matched, HIV-seropositive, HTLV-seronegative controls (single infection). <h3>Results.</h3> —Variables independently associated with coinfection included higher CD4⁺lymphocyte count (odds ratio [OR], 2.3; 95% confidence limits [CL], 1.3,4.1), higher CD4⁺percentage (OR, 2.0; 95% CL, 1.3, 3.2), β₂-microglobulin level of 254 nmol/L or more (OR, 6.8; 95% CL, 1.3, 35.4), World Health Organization stages 3 and 4 (OR, 4.4; 95% CL, 1.1,18.0), and reporting a parenteral risk factor (OR, 7.4; 95% CL, 1.4, 38.9). When stratified by p24 antigenemia, coinfection was associated with an estimated 82% higher CD4⁺lymphocyte count (<i>P</i>&lt;.05). <h3>Conclusion.</h3> —Coinfection was associated with higher CD4⁺lymphocyte counts, more advanced clinical disease, and higher β₂-microglobulin levels than HIV infection alone. The higher mean CD4⁺lymphocyte count does not appear to offer immunologic benefit. Caution should be exercised when using CD4⁺lymphocytes as a surrogate marker in studies of HIV infection in populations where HTLV-I is prevalent. Further studies are needed to address whether current CD4⁺lymphocyte values for the initiation of antiretroviral therapy and chemoprophylaxis against opportunistic infections in HIV infection are appropriate in coinfection. (<i>JAMA</i>. 1994;271:353-357)