Differences in Muscle Quantity and Quality by HIV Serostatus and Sex.

OBJECTIVE: People with HIV (PWH) experience greater declines in both muscle function and muscle mass with aging. Whether changes in muscle quality and quantity with aging differ between men and women with HIV and the implications on muscle function are not established. DESIGN: In coordinated substudies of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study, participants completed physical function and falls assessments; total trunk/thigh density, inversely related to fatty infiltration, and area were quantified from computed tomography (CT) scans. METHODS: Generalized linear models were used to explore variables affecting density/area, and associations between area/density and physical function and falls. RESULTS: CT scans were available on 387 men (198 PWH) and 184 women (118 PWH). HIV serostatus was associated with greater lateralis, paraspinal, and hamstring area, but lower psoas area and density. Older age and female sex were associated with smaller trunk muscle area and lower density. Both lower muscle area and muscle density were associated with several measures of impaired physical function. The odds of falling were lower with greater hamstring density, but not associated with other measurers of muscle area or density. CONCLUSIONS: In summary, older adults with HIV appear to have smaller and less dense (fattier) psoas, a key component in truncal stability and hip flexion that could have implications on physical function. The longitudinal associations of muscle area and density with physical function require careful investigation, with a particular focus on characteristics and interventions that can preserve muscle area, density, and function over time.

Factors and methods to modulate DNA hybridization kinetics.

DNA oligonucleotides are widely used in a diverse range of research fields from analytical chemistry, molecular biology, nanotechnology to drug delivery. In these applications, DNA hybridization is often the most important enabling reaction. Achieving control over hybridization kinetics and a high yield of hybridized products is needed to ensure high-quality and reproducible results. Since DNA strands are highly negatively charged and can also fold upon itself to form various intramolecular structures, DNA hybridization needs to overcome these barriers. Nucleation and diffusion are two main kinetic limiting steps although their relative importance differs in different conditions. The effects of length and sequence, temperature, pH, salt concentration, cationic polymers, organic solvents, freezing and crowding agents are summarized in the context of overcoming these barriers. This article will help researchers in the biotechnology-related fields to better understand and control DNA hybridization, as well as provide a landscape for future work in simulation and experiment to optimize DNA hybridization systems.

Guidance for Health Risk Assessment at Recurrent Mass Gatherings: The Jeddah Tool Framework.

A wide range of natural and man-made hazards increases the health risks at mass gatherings (MGs). Building on the Sendai Framework for Disaster Risk Reduction 2015-2030, the World Health Organization (WHO) developed the Health Emergency and Disaster Risk Management (H-EDRM) framework to strengthen preparedness, response, and recovery from health emergencies in the communities and emergency-prone settings, such as MGs. The Jeddah tool is derived from the H-EDRM framework as an all-hazard MG risk assessment tool, which provides a benchmark for monitoring progress made in capacity strengthening over a given period for recurrent MGs. Additionally, it introduces a reputational risk assessment domain to complement vulnerability and capacity assessment matrixes. This paper describes the key elements of the Jeddah tool to improve the understanding of health risk assessment at MGs in the overarching contexts of health emergencies and disaster risk reduction, in line with international goals.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

OBJECTIVES: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. METHODS: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. RESULTS: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. CONCLUSIONS: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity.

OBJECTIVES: Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. DESIGN: Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. METHODS: Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. RESULTS: HIV+ men had denser SAT (-95 vs -98 HU HIV-, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV-, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV- men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. CONCLUSIONS: Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

To T or not to T: Differences in Testosterone Use and Discontinuation by HIV Serostatus among Men who Have Sex with Men.

OBJECTIVES: The aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). METHODS: Self-reported testosterone use data were collected semiannually from 2400 (1286 HIV-infected and 1114 HIV-uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012-2015). RESULTS: Use was higher among HIV-infected compared with HIV-uninfected men in all age strata, with an age-adjusted prevalence of 17% vs. 5%, respectively (adjusted prevalence ratio 3.7; P < 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non-smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high-risk category). Compared with HIV-uninfected men, HIV-infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person-years [95% confidence interval (CI) 17.3, 25.0/100 person-years]. Relative to HIV-uninfected men, HIV-infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P < 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co-factors (P = 0.06). CONCLUSIONS: Given the high prevalence of both TTh use and CVD risk among HIV-infected men, the benefits and risks of TTh should be examined in future studies of aging HIV-infected men and monitored routinely in clinical practice.

Strengthening health security at the Hajj mass gatherings: characteristics of the infectious diseases surveillance systems operational during the 2015 Hajj.

BACKGROUND: Hajj is one of the largest and the most ethnically and culturally diverse mass gatherings worldwide. The use of appropriate surveillance systems ensures timely information management for effective planning and response to infectious diseases threats during the pilgrimage. The literature describes infectious diseases prevention and control strategies for Hajj but with limited information on the operations and characteristics of the existing Hajj infectious diseases surveillance systems. METHOD: We reviewed documents, including guidelines and reports from the Saudi Ministry of Health's database, to describe the characteristics of the infectious diseases surveillance systems that were operational during the 2015 Hajj, highlighting best practices and gaps and proposing strategies for strengthening and improvement. Using Pubmed and Embase online search engines and a combination of search terms including, 'mass gatherings' 'Olympics' 'surveillance' 'Hajj' 'health security', we explored the existing literature and highlighted some lessons learnt from other international mass gatherings. RESULTS: A regular indicator-based infectious disease surveillance system generates routine reports from health facilities within the Kingdom to the regional and central public health directorates all year round. During Hajj, enhanced indicator-based notifiable diseases surveillance systems complement the existing surveillance tool to ensure timely reporting of event information for appropriate action by public health officials. CONCLUSION: There is need to integrate the existing Hajj surveillance data management systems and to implement syndromic surveillance as an early warning system for infectious disease control during Hajj. International engagement is important to strengthen Hajj infectious diseases surveillance and to prevent disease transmission and globalization of infectious agents which could undermine global health security.

HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS).

OBJECTIVES: HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown. METHODS: We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography. RESULTS: HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01). CONCLUSIONS: Among men with CAC scores of zero, HIV infection is associated with an increased prevalence of noncalcified coronary plaque independent of traditional cardiovascular risk factors. This finding suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

Low free testosterone in HIV-infected men is not associated with subclinical cardiovascular disease.

OBJECTIVES: Low testosterone (T) is associated with cardiovascular disease (CVD) and increased mortality in the general population; however, the impact of T on subclinical CVD in HIV disease is unknown. This study examined the relationships among free testosterone (FT), subclinical CVD, and HIV disease. METHODS: This was a cross-sectional analysis in 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. Main outcomes were coronary artery calcification presence, defined as a coronary artery calcium (CAC) score >10 (CAC score was the geometric mean of the Agatston scores of two computed tomography replicates), and far wall common carotid intima-media thickness (IMT)/carotid lesion presence by B-mode ultrasound. RESULTS: Compared with the HIV-uninfected men in our sample, HIV-infected men were younger, with lower body mass index (BMI) and more often Black. HIV-infected men had lower FT (age-adjusted FT 88.7 ng/dL vs. 101.7 ng/dL in HIV-uninfected men; P=0.0004); however, FT was not associated with CAC, log carotid IMT, or the presence of carotid lesions. HIV status was not associated with CAC presence or log carotid IMT, but was associated with carotid lesion presence (adjusted odds ratio 1.69; 95% confidence interval 1.06, 2.71) in HIV-infected men compared with HIV-uninfected men. CONCLUSIONS: Compared with HIV-uninfected men, HIV-infected men had lower FT, as well as more prevalent carotid lesions. In both groups, FT was not associated with CAC presence, log carotid IMT, or carotid lesion presence, suggesting that FT does not influence subclinical CVD in this population of men with and at risk for HIV infection.

Culture and psychosocial function in british and Japanese people with an ostomy.

PURPOSE: We compared social and psychological adjustment to surgery ending with an ostomy in British and Japanese patients. METHODS: In response to a postal survey, 948 ostomy patients (464 British and 484 Japanese), selected at random from respective national databases, provided assessable data on the Ostomy Adjustment Inventory-23 (OAI-23), a validated scale for measurement of psychosocial adjustment to an ostomy. RESULTS: Analysis of variance revealed that country of residence (F1,876 = 50.9, P < .001) and time since surgery (F3,876 = 9.9, P < .001) significantly influenced psychosocial adjustment to an ostomy. British persons with an ostomy experienced higher psychosocial adjustment to an ostomy than did Japanese respondents. Multivariate analysis based on acceptance, social engagement, anxious-preoccupation, and anger also found that country of residence and time since surgery influenced psychosocial adjustment (Pillai's Trace: V = 0.22, F = 67.15, P < 0.001, and V = 0.05, F = 3.6, P ≤ .001, respectively). Acceptance and social engagement (discriminant coefficient = 0.92 and 0.56, respectively) made the largest contribution. CONCLUSION: Psychosocial functioning differed in British and Japanese persons with an ostomy, suggesting that culture influences psychosocial adjustment to life with an ostomy. These findings support the need for culturally informed ostomy care.

Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men.

BACKGROUND: The purpose of this study was to evaluate the relationship between cognitive performance, risk factors for cardiovascular and cerebrovascular disease (CVD), and HIV infection in the era of highly active antiretroviral therapy. METHODS: We evaluated the cognitive functions of men enrolled in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study who were aged > or =40 years, with no self-reported history of heart disease or cerebrovascular disease. Results from comprehensive neuropsychological evaluations were used to construct composite scores of psychomotor speed and memory performance. Subclinical CVD was assessed by measuring coronary artery calcium and carotid artery intima-media thickness (IMT), as well as laboratory measures, including total cholesterol, fasting glucose, glycosylated hemoglobin, glomerular filtration rate (estimated), and standardized blood pressure and heart rate measures. RESULTS: After accounting for education, depression, and race, carotid IMT and glomerular filtration rate were significantly associated with psychomotor speed, whereas IMT was associated with memory test performance. HIV serostatus was not significantly associated with poorer cognitive test performance. However, among the HIV-infected individuals, the presence of detectable HIV RNA in plasma was linked to lower memory performance. CONCLUSIONS: These findings suggest that HIV infection may not be the most important predictor of cognitive performance among older gay and bisexual men in the post-highly active antiretroviral therapy era, at least among those with access to medical care and to appropriate medications. Medical factors associated with normal aging are significantly associated with performance on neuropsychological tests, and good clinical management of these factors both in HIV-infected individuals and those at risk for infection may have beneficial effects in the short term and could reduce the risk of subsequent cognitive decline.

Development and psychometric evaluation of the Ostomy Adjustment Inventory-23.

PURPOSE: This article describes the development of the Ostomy Adjustment Inventory-23 (OAI-23), a self-report, multidimensional scale designed to assess psychosocial adjustment in patients with ostomy. SUBJECTS AND SETTING: Five hundred seventy persons with a colostomy, ileostomy, or urostomy, who were randomly selected from 3 national databases, provided assessable data. RESULTS: The results indicate that the OAI-23 is reliable (the Cronbach alpha = .93, split-half = 0.91, and test-retest (r) = 0.83) and valid, correlating positively with Felton's Acceptance of Illness Scale (r = 0.72) and confirming expected improvements in adjustment consistent with increasing time since surgery (F 5,531 = 5.22, P < .001). Four factors (eigenvalue >or= 1) that accounted for 55.4% of the total variance emerged from factor analysis. CONCLUSION: The OAI-23 is a valid and reliable measure of psychosocial adjustment that will be of interest to both researchers investigating life after stoma surgery and clinicians making objective assessments of their patients' progress.

Adjustment to colostomy: stoma acceptance, stoma care self-efficacy and interpersonal relationships.

AIM: This paper is a report of a study to examine adjustment and its relationship with stoma acceptance and social interaction, and the link between stoma care self-efficacy and adjustment in the presence of acceptance and social interactions. BACKGROUND: There have been significant advances in stoma appliances and an increase in nurses specialising in stoma care. Despite this, a large proportion of patients continue to experience adjustment problems, which suggests that improvements in the management of the stoma are by themselves not enough to enhance psychosocial functioning. Illness acceptance and interpersonal relationships are widely reported as correlates of adjustment to chronic illness, but these have not been specifically examined in patients with a colostomy. Evidence of their association could offer stoma therapists alternative ways of aiding adjustment. METHOD: Between 2000 and 2002, 51 patients with colostomies provided demographic and clinical data and completed validated questionnaires to measure acceptance of the stoma, relationship with others and stoma care self-efficacy 6 months after surgery. FINDINGS: Multiple regression analysis showed that stoma care self-efficacy, stoma acceptance, interpersonal relationship and location of the stoma were strongly associated with adjustment. The model explained 77% of the variance. Stoma-care self-efficacy accounted for 57.5%, the psychosocial variables 13% and location of the stoma 4.6%. The addition of gender, which was not statistically significant (P > 0.05), explained a further 1.9% of the variance. CONCLUSION: Addressing psychosocial concerns should become part of the care routinely given to stoma patients. We recommend more emphasis on dispelling negative thoughts and encouraging social interactions.

Longitudinal changes in serum lipids among HIV-infected men on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up. METHODS: A total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points. RESULTS: Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (<1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation. CONCLUSIONS: Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.

Effects of lipodystrophy on quality of life and depression in HIV-infected men on HAART.

The aim of the study was a prospective assessment of the possible consequences of a diagnosis of lipodystrophy on health-related quality of life (HRQL) and depressive symptomatology in HIV-seropositive men who have sex with men. A standardized physical assessment for lipodystrophy was introduced within a prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV-seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of HRQL and depression. A series of questionnaires, which included the Medical Outcomes Study Short-Form 36 (SF-36) and the Center for Epidemiological Studies-Depression (CES-D), were administered to assess HRQL and depression, respectively. SF-36 scores were summarized using the mental and physical components; CES-D results were reported as both dichotomous (with or with clinical depression) and continuous scores. Neither the mental nor physical components of the SF-36 showed any significant differences between patients with lipodystrophy versus HIV-seropositive patients without lipodystrophy. Similarly, lipodystrophy status was not significantly associated with either continuous depression scores or presence of clinical depression. However, consistent with previous results, HIV-seropositive men without lipodystrophy (compared to HIV-seronegative men) reported higher scores on both components of the SF-36 scales and both categorizations of the CES-D. The results of this study suggest that lipodystrophy does not negatively affect HRQL or depression, above and beyond, the diagnosis of HIV infection, although the impact of the severity of lipodystrophy on these conditions will require further study.

Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences.

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viral env from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C(IN). Overall, C(IN) lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-C(IN) sequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins.

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.