Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

Adherence to Daily Oral TDF/FTC for PrEP in Community Health Center Populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study.

The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0-1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0-1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09-2.34) or "Other" race (RR 1.62, CI 0.99-2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33-4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level.

Associations between oral health and general health: a surveywide association study of the NHANES.

OBJECTIVE: This proof of concept study uses data from the National Health and Nutrition Examination Survey (NHANES) to explore potential associations between oral and systemic health in a survey-wide association study (SWAS). BASIC RESEARCH DESIGN: Data from n=9,971 records in the 2015-2016 NHANES survey were used to evaluate associations between self-rated oral health and the various systemic health conditions that are included in the survey. Associations were estimated using survey-weighted linear regression models adjusted for age, sex, race, and smoking status. RESULTS: Substantial associations with self-rated oral health were evident after correction for multiple comparisons. The study revealed associations in categories of mental health, cardiovascular disease, and diabetes adding to the body of evidence. The study also suggested associations with physical functioning, vision, hearing, genitourinary symptoms, and the prevalence of hepatitis. CONCLUSIONS: The SWAS method demonstrated the ability to identify associations between oral health and systemic health. Suggested associations should be investigated further investigated with emphasis on both biologic and societal mechanisms. The noteworthy associations with mental health, physical activity, and cardiovascular disease in this study inform clinicians from each of these disciplines that they may benefit from collaborations with oral health care providers to promote whole-person health.

A potential role for protein O-fucosylation during pollen-pistil interactions.

Putative protein O-fucosyltransferases (POFTs) represent a large family of Glycosyl Transferase family 65 domain-containing proteins in land plants, with at least 39 proposed members in the Arabidopsis thaliana genome alone. We recently identified a member of this family, AtOFT1 (At3g05320), in which loss-of-function mutants display impaired sexual reproduction that was linked to a defective male gamete. Specifically, oft1 mutant pollen tubes are ineffective at penetrating the stigma-style interface leading to a drastic reduction in seed set and a nearly 2000-fold reduction in pollen transmission. Our findings establish that AtOFT1 plays a critical role in pollen tube penetration through the stigma/style in Arabidopsis and further suggest an important role for protein O-glycosylation events that potentially influence pollen tube mechanical strength or the ability to respond to positional guidance cues during the process of tube growth and fertilization.

Perceptions of Door-to-Door HIV Counselling and Testing in Botswana

Prevalence of HIV infection in Botswana is among the highest in the world; at 23.9 of 15 - 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana. Community members associated many positive benefits with home-based; door-to-door HIV testing; including convenience; confidentiality; capacity to increase the number of people tested; and opportunities to increase knowledge of HIV transmission; prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict; coercion; stigma; and psychological distress within households. Community members emphasised the need for individual and community preparation; including procedures to protect confidentiality; provisions for psychological and social support; and links to appropriate services for HIV-positive persons

A non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infection.

The type I interferon (IFN-alpha/beta) receptor 1 (IFNAR1) mediates the potent antiviral and immuno-regulatory effects of IFN-alpha/beta that are believed to be pivotal to eradicate hepatitis B virus (HBV) infection. IFNAR1 promoter polymorphisms (at -568/-77) have been shown to be associated with susceptibility to chronic HBV infection; however, whether these markers are genetic determinants of HBV infection remains unknown. The functional significance of promoter -568/-77 polymorphisms was assessed by mutagenesis and luciferase assays. Sequencing and restriction fragment length polymorphisms in 328 chronic HBV patients, 130 spontaneous resolvers and 148 healthy blood donors identified other polymorphism at IFNAR1 open reading frame. IFNAR1 expression levels in peripheral blood cells were detected by flow cytometry. We found that the -568/-77 promoter variants were unlikely to affect transcription levels. A C/G single nucleotide polymorphism, in strong linkage disequilibrium with the promoter polymorphisms, was found in the coding sequence of IFNAR1 (nt19158). This resulted in a nonsynonymous substitution in the extracellular region of IFNAR1 protein and correlated with susceptibility to chronic HBV infection. Bioinformatic analysis suggested decreased stability of the IFNAR1 protein. Chronic HBV patients with the 19158C/C genotype (Leu141) exhibited higher IFNAR1 protein expression levels in peripheral blood monocytes than those with the 19158G/G genotype (Val141). In conclusion, IFNAR1 19158C/G polymorphism is primarily associated with susceptibility to chronic HBV infection.

Central role of detachment faults in accretion of slow-spreading oceanic lithosphere.

The formation of oceanic detachment faults is well established from inactive, corrugated fault planes exposed on sea floor formed along ridges spreading at less than 80 km Myr(-1) (refs 1-4). These faults can accommodate extension for up to 1-3 Myr (ref. 5), and are associated with one of the two contrasting modes of accretion operating along the northern Mid-Atlantic Ridge. The first mode is asymmetrical accretion involving an active detachment fault along one ridge flank. The second mode is the well-known symmetrical accretion, dominated by magmatic processes with subsidiary high-angle faulting and the formation of abyssal hills on both flanks. Here we present an examination of approximately 2,500 km of the Mid-Atlantic Ridge between 12.5 and 35 degrees N, which reveals asymmetrical accretion along almost half of the ridge. Hydrothermal activity identified so far in the study region is closely associated with asymmetrical accretion, which also shows high levels of near-continuous hydroacoustically and teleseismically recorded seismicity. Increased seismicity is probably generated along detachment faults that accommodate a sizeable proportion of the total plate separation. In contrast, symmetrical segments have lower levels of seismicity, which occurs primarily at segment ends. Basalts erupted along asymmetrical segments have compositions that are consistent with crystallization at higher pressures than basalts from symmetrical segments, and with lower extents of partial melting of the mantle. Both seismic evidence and geochemical evidence indicate that the axial lithosphere is thicker and colder at asymmetrical sections of the ridge, either because associated hydrothermal circulation efficiently penetrates to greater depths or because the rising mantle is cooler. We suggest that much of the variability in sea-floor morphology, seismicity and basalt chemistry found along slow-spreading ridges can be thus attributed to the frequent involvement of detachment faults in oceanic lithospheric accretion.

Assessing field-scale migration of radionuclides at the Nevada Test Site: "mobile" species.

Many long-lived radionuclides are present in groundwater at the Nevada Test Site (NTS) as a result of 828 underground nuclear weapons tests conducted between 1951 and 1992. In conjunction with a comprehensive geochemical review of radionuclides (3H, 14C, 36Cl, 99Tc and 129I) that are presumably mobile in the subsurface, we synthesized a body of radionuclide activity data measured from groundwater samples collected at 18 monitoring wells, to qualitatively assess their migration at the NTS over distances of hundreds of meters and over timescales of decades. Tritium and 36Cl showed little evidence of retardation, while the transport of 14C may have been retarded by its isotopic exchange with carbonate minerals in the aquifer. Observed local reducing conditions (either natural or test-induced) will impact the mobility of certain redox-sensitive radionuclides (especially 99Tc) that were otherwise soluble and readily transported under oxidizing conditions. Conversely, strongly oxidizing conditions may impact the mobility of 129I which is mobile under reducing conditions. The effect of iodine speciation on its transport deserves further attention. Indication of delayed transport of some "mobile" radionuclides (especially 99Tc) in the groundwater at the NTS suggested the importance of redox conditions of the natural system in controlling the fate and transport of radionuclides, which has implications in the enhanced performance of the potential Yucca Mountain repository, located adjacent to the NTS, to store high-level nuclear wastes as well as management of radionuclide contamination in legacy nuclear operations facilities.

A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene.

Osteoporosis pseudoglioma syndrome (OPPG) is an autosomal recessive disorder due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we report two novel missense mutations found in a southern Chinese family of a non-consanguineous marriage. Three out of four children had blindness, low bone mineral density (BMD) and multiple fractures in their childhood. Genotyping by DNA sequencing demonstrated 2 new mutations in exon 7 of the LRP5 gene. Tryptophans at amino acid residue positions 478 and 504 were replaced by arginine (W478R) and cysteine (W504C), respectively. While the parents that possessed either heterozygous W478R or W504C were apparently normal, all affected subjects were compound heterozygotes for the W478R and W504C mutations in the LRP5 gene. W478R is located immediately C-terminal to the third YWTD repeat of the second YWTD/EGF domain in LRP5, while W504C is located between the third and the fourth YWTD repeats of the second YWTD/EGF domain in LRP5. Using LRP5-related proteins, such as the low-density lipoprotein receptor (LDLR) and nidogen as reference models, a homology model of LRP5 suggested that the observed mutations may affect the molecular interactions of LRP5 and so lead to the observed OPPG phenotypes.

An inventory of long-lived radionuclides residual from underground nuclear testing at the Nevada test site, 1951-1992.

An inventory of long-lived radionuclides produced by 828 underground nuclear tests conducted at the Nevada test site (NTS) from 1951 to 1992 includes residual tritium, fission products, actinides, and activation products. Recently, the US Department of Energy approved the declassification of the NTS radionuclide inventory by principal geographic test centers. This permits unclassified publication of radionuclide totals for the Yucca Flat, Pahute Mesa-Area 19, Pahute Mesa-Area 20, Frenchman Flat, and Rainier Mesa/Shoshone Mountain testing locations. Activities are reported as of September 23, 1992, the date of the last underground nuclear test conducted at the NTS, and September 23, 2492, after 500 years of radioactive decay. The availability of these data affords an opportunity for the analysis of the radiologic source term within the boundaries of local hydrogeologic units and provides insight to where radionuclides are sited relative to potential exposure pathways.

Regional variation in CCR5-Delta32 gene distribution among women from the US HIV Epidemiology Research Study (HERS).

The CCR5-Delta32 genotype is known to influence HIV-1 transmission and disease. We genotyped 1301 US women of various races/ethnicities participating in the HIV Epidemiologic Research Study. None was homozygous for CCR5-Delta32. The distribution of heterozygotes was similar in HIV-1 infected and uninfected women. Thirty-seven (11.8%) white, 28 (3.7%) blacks/African Americans (AA), seven (3.3%) Hispanics/Latinas, and one (6.6%) other race/ethnicity were heterozygous. The frequency of heterozygotes differed among sites for all races combined (P = 0.001). More heterozygotes were found in AA women in Rhode Island (8.9%) than in the other sites (3.1%) (P = 0.02), while heterozygosity in white women was most common in Maryland (28.6%) (P = 0.025). These regional differences could be accounted for by racial admixture in AAs, but not in whites. Regional variations should be considered when studying host genetic factors and HIV-1 in US populations.

Rapid diagnostic evaluation of bronchial washings in patients with suspected coccidioidomycosis.

Coccidioidomycosis is a regionally common fungal infection, primarily affecting the lung. While in the majority of cases the tempo of the disease allows for a more leisurely diagnostic plan, including multiple serologic tests and culture of respiratory secretions, occasionally, patients will present with rapidly progressive, life-threatening pulmonary illness, in whom there is an urgent need for rapid diagnosis. Evaluation of respiratory secretions including expectorated sputum as well as bronchial washings are frequently available or obtained for diagnosing pulmonary infiltrates. We compared the sensitivity of the Papanicolaou stain with 10% potassium hydroxide digestion (10% KOH) and with calcofluor white (cw). The Papanicolaou test performed the best and should be used in the evaluation of suspected patients with coccidioidomycosis.

Cancer incidence in women with or at risk for HIV.

The purpose of our study was to identify the types and rates of cancers seen in high-risk human immunodeficiency virus (HIV)-infected and HIV-uninfected women. From 1993 to 1995, 1,310 women enrolled at four urban U.S. research sites in the HIV Epidemiology Research Study and were interviewed biannually to identify interval diagnoses and hospitalizations until study closure in March 2000. Cancer incidence data were collected through abstraction of medical records and death certificates. Of 871 HIV-infected and 439 HIV-uninfected women, 85% had a history of smoking and 50% a history of injection drug use. For our analysis, 4,180 person-years were contributed by HIV-infected women, and 2,308 person-years by HIV-uninfected women. HIV-infected women had 8 non-Hodgkin's lymphomas, 5 invasive cervical cancers (ICC), 1 Kaposi's sarcoma and 12 non-AIDS defining cancers, including 4 lung cancers, compared with 4 cancers in HIV-uninfected women including 1 lung cancer (all cancers, 6.22/1000 person-years vs. 1.73/1000 person-years, p = 0.01). CD4+ cell counts were above 200/mm3 in all women with ICC. HIV-infected women with lung cancer were young smokers (mean age, 40 years), and all died within 6 months of diagnosis. Lung cancer occurred at twice the rate in HIV-infected vs. uninfected women in the cohort and severalfold above expected in age- and race-matched women in U.S. national data (incidence relative risk 6.39; 95% confidence interval 3.71, 11.02; p < 10(-7)). The frequent occurrence of cervical and lung cancers have important implications for the counseling (cigarette cessation), screening (PAP smears) and care of women with HIV infection, as they live longer because of current antiretroviral therapies.

Influence of injection drug use behavior on reported antiretroviral therapy use among women in the HIV Epidemiology Research study: on-site versus referral care.

BACKGROUND: HIV-infected injection drug users consistently report poor antiretroviral therapy use and little contact with health care providers. It has been suggested that the clinical setting where patients are seen affects the use of highly active antiretroviral therapy. OBJECTIVES: The purpose of this study was to determine whether ease of access to medical care affects self-report of taking antiretroviral therapy, particularly among female injection drug users. DESIGN: The study is a cross-sectional analysis from a prospective cohort study of HIV-infected women. SETTING: Women were enrolled at four sites in the United States: Detroit, Michigan, and Providence, Rhode Island, where on-site HIV care and treatment were offered, and Baltimore, Maryland, and the Bronx, New York, where all participants were referred elsewhere for HIV care and treatment. PATIENTS: Patients were HIV-infected women with no AIDS diagnosis or women who were at risk for HIV infection either through self-reported injection drug use since 1985 or through sexual contact. MEASUREMENTS: The study measured self-reported use of antiretroviral therapy (ART) alone or combined with Pneumocystis carinii (PCP) prophylaxis in the previous 6 months. RESULTS: In multivariate analysis including type of study site (on-site compared with referral care) and injection drug use, any self-reported ART use associated with low CD4 cell count category, older age, and race. However, at on-site care centers, women were equally likely to report ART use regardless of current, former, or no injection drug use, whereas at referral sites only women identified as sexual contacts were more likely to report any ART use, independent of all other variables. CONCLUSIONS: Easy access to medical care has an important impact on HIV-infected women receiving ART, particularly those who are active injection drug users.

Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the her study.

BACKGROUND: Research regarding treatment adherence in chronic diseases, such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS. OBJECTIVE: To examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past 1 and 3 days). METHODS: Cross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study. RESULTS: Seventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education. CONCLUSIONS: Self-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence.

A dendritic active site: catalysis of the Henry reaction.

[reaction: see text] Dendrimers containing an encapsulated tertiary amine were prepared by coupling tris(2-aminoethyl)amine with dendritic branches derived from L-lysine. These dendrimers were used as catalysts in the Henry (nitroaldol) reaction between 4-nitrobenzaldehyde and nitroethane, and their catalytic performance was compared with that of triethylamine. Attachment of the dendritic shell alters the rate of reaction and influences the syn:anti ratio of products. It is proposed that the dendritic shell generates an encapsulated catalytically active site, mimicking the behavior of a protein superstructure.

A nursing shortage: building organizational commitment among nurses.

As a major nursing shortage threatens healthcare organizations, the views of 30 staff nurses are examined to determine factors that contribute to their commitment, or lack of commitment, to their employing hospital. Content analysis identified that organizational commitment is most related to personal factors, opportunities for learning, job satisfaction, plan for retirement, monetary benefits, patient care, coworkers, cultural factors, and job security, in that order. Lack of organizational commitment is most related to conflict with personal needs. However, lack of learning, lack of appreciation and fairness, inadequate monetary benefits, patient care situations, poor relations with coworkers, career developmental stage, and lack of job security are also discussed. Application of these findings to healthcare administration is discussed, with strategies for building organizational commitment among nurses.

Staff nurse views of their productivity and nonproductivity.

Could better collaboration and cooperation to improve productivity occur between administrators and nurses if we understood nurse views of their productivity? Interviews of 30 staff nurses revealed that these nurses evaluated their productivity by the quantity and quality of their work. Working hard, finishing everything, and providing excellent care made them feel productive, while anything that interfered with this was a source of feeling nonproductive.

Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

Multicenter evaluation of hepatitis C RNA levels among female injection drug users.

The purpose of this investigation was to identify factors that determine the blood level of hepatitis C virus (HCV) RNA. By use of a quantitative polymerase chain reaction assay, the level of HCV RNA was ascertained in stored serum samples from 676 women enrolled in a multicenter prospective investigation who were seropositive for anti-HCV antibodies. HCV RNA levels ranged from undetectable to 22.4x106 copies/mL in these women. Among the 520 women with detectable HCV RNA, levels were higher among those who were >41 years old and those who had human immunodeficiency virus (HIV) infection. After adjusting for age in a multivariate linear regression model, HCV RNA levels were more strongly associated with HIV RNA levels than with CD4(+) lymphocyte counts. However, <6% of person-to-person variance was explained by the factors evaluated. Additional research is needed to ascertain what determines the level of HCV RNA in blood.