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Background: Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH)., Methods: This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models., Results: PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34)., Conclusions: Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted., Competing Interests: Potential conflicts of interest. M. C. reports research grants from Gilead, MSD, and ViiV (paid to institution); payment for expert testimony from Gilead, MSD, and ViiV Healthcare (paid to institution); and support for attending meetings and/or travel from Gilead (paid to institution). C. B. H. reports grants or contracts from Gilead (payments to institution for unrelated research). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In December 2015, the men who have sex with men (MSM) deferral was reduced to 12 months in the United States. We compared human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) incidence and residual risk before and after this policy change using data from >50% of the US blood supply., Study Design and Methods: Three estimation intervals from the Transfusion-Transmissible Infections Monitoring System were compared: 15-months pre- and two consecutive, nonoverlapping 15-month post-MSM deferral implementation. Repeat, first-time, and weighted all-donor incidences were estimated. Residual risk was calculated for all incidence estimates using the incidence/window-period method., Results: HIV repeat donor incidence was 1.57 per 100 000 person-years (phtpy) in the second 15-month post change and not significantly different from pre-MSM incidence of 2.19 phtpy. Similar values were seen for HCV (1.49 phtpy vs 1.46 phtpy) and HBV (1.14 phtpy vs 0.97 phtpy). In some cases, higher estimated incidence, but without significant change from pre-MSM to the second post change period occurred for males and first-time donors (eg, first-time donors, second post change period: 6.12 phtpy HIV, 6.41 phtpy HCV and 5.34 phtpy HBV). Estimated per donation residual risk was 1:1.6 million for HIV, 1:2.0 million for HCV and 1:1.0 million for HBV based on weighted incidence for all donors., Conclusions: Repeat, first-time, and overall donor incidence did not vary significantly comparing pre-MSM to either of the post-MSM estimation intervals. Residual risk estimates vary by study, but all yield residual risks in the United States of ≤1 per million, and thus far have not shown increasing risk with the 12-month MSM policy change., (© 2021 AABB.)

Background: Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care., Methods: Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes., Results: 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year., Conclusions: Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants., (© 2020 by the Research Society on Alcoholism.)

Background: The Transfusion-Transmissible Infections Monitoring System (TTIMS) combines data from four US blood collection organizations including approximately 60% of all donations to monitor demographic and temporal trends in infectious disease markers and policy impacts., Study Design and Methods: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) consensus-positive definitions combined serology and nucleic acid testing results. These along with donor and donation characteristics were assembled into a single data set. Overall donation prevalence and demographic subsets were compared pre- and post-implementation of the 2015 change in men who have sex with men (MSM) deferral policy, among other prevalence comparisons., Results: From October 2015 to September 2019, there were 712 HIV-, 1735 HBV-, and 5217 HCV-positive samples identified from approximately 27.5 million donations (>9.4 million donors). Prevalences per 100 000 donations were 2.6 (HIV), 6.3 (HBV), and 19.0 (HCV), and the highest for all three agents were in donations from first-time male donors. Two slight but significant increases in HIV prevalence were observed, both for comparisons of Year 1 (pre-MSM policy change) versus Year 4 (post-MSM policy change) for first-time males and first-time females; in contrast, similar comparisons demonstrated decreases in HCV prevalence (all donors and general trends for males and females). Except for HIV, prevalence increased with age; for all agents, prevalence was markedly higher in the south., Conclusions: No major trends were observed over 4 years covering the MSM policy change from indefinite to a 12-month deferral, but ongoing monitoring is warranted. Demographic trends are consistent with those observed in other donor studies and community trends., (© 2020 AABB.)

Background: Monitoring of transfusion-transmissible infections in the blood supply is essential for blood safety, as the donor population is not static, and changes in policy, donor behavior, or other factors could increase the risk of recipient infection. We assessed patterns of recently acquired HIV infection in US blood donors, including before and after the implementation of the 12-month deferral for men who have sex with men (MSM)., Study Design and Methods: A large convenience sample of donations from donors testing HIV-1 nucleic acid testing (NAT) and serology-reactive were further tested with the Sedia HIV-1 Limiting Antigen enzyme immunoassay. Samples were analyzed across available demographic and donation data to provide an assessment of recently acquired HIV infection in US blood donors from 2010 to 2018., Results: Overall, 317 of 1154 (27.5%; 95% confidence interval, 24.9%-30.1%) donations from HIV NAT and serology-reactive donors had recently acquired HIV infection. There was no evidence of change in the percentages of recent HIV infection by year over the study period, either in all donors or in male donors, including after the MSM policy change. In multivariable logistic regression analysis, donors aged 24 years or younger were over 2.7 times more likely and repeat donors 2.2 times more likely to have recently acquired HIV infection compared to donors aged 55 years or older and first-time donors, respectively., Conclusion: Patterns of recently acquired HIV infection varied by demographics but not over time. These findings suggest no impact of the MSM policy change on recently acquired HIV infection in US blood donors., (© 2020 AABB.)

In 2015, the US Food and Drug Administration published revised guidance that recommended a change in blood donor deferral of men who have sex with men (MSM) from an indefinite to a 12-month deferral since the donor last had sex with a man. We assessed whether HIV incidence in first-time blood donors or associated transfusion risk increased. Donations in 4 major blood collection organizations were monitored for 15 months before and 2 years after implementation of the 12-month MSM deferral policy. HIV-positive donations were classified as recently acquired or long-term using a recent infection testing algorithm and incidence in both periods estimated. Residual transfusion transmission risk was estimated by multiplying incidence by the length of the infectious window period. The latter was estimated using a model based on infectious dose and the sensitivity of nucleic acid testing. Factors associated with incident infection in each period were assessed using Poisson regression. Overall HIV incidence in first-time donors before implementation of the 12-month MSM deferral was estimated at 2.62 cases per 100 000 person-years (105 PY) (95% credible interval [CI], 1.53-3.93 cases/105 PY), and after implementation at 2.85 cases/105 PY (95% CI, 1.96-3.93 cases/105 PY), with no statistically significant change. In male first-time donors, the incidence difference was 0.93 cases/105 PY (95% CI, -1.74-3.58 cases/105 PY). The residual risk of HIV transfusion transmission through components sourced from first-time donors was estimated at 0.32 transmissions per million (106) packed red blood cell transfusions (95% CI, 0.29-0.65 transmissions/106 transfusions) before and 0.35 transmissions/106 transfusions (95% CI, 0.31-0.65 transmissions/106 transfusions) after implementation. The difference was not statistically significant. Factors associated with incident infection were the same in each period. We observed no increase in HIV incidence or HIV transfusion transmission risk after implementation of a 12-month MSM deferral policy.

Antiretroviral therapy (ART) to treat and pre-exposure prophylaxis (PrEP) to prevent HIV infection are effective tools to help end the HIV epidemic. However, their use could affect HIV transfusion-transmission risk. Three different ART/PrEP prevalence analyses in blood donors were conducted. First, blood samples from HIV-positive and a comparison group of infection-nonreactive donors were tested under blind using liquid chromatography-tandem mass spectrometry for ART. Second, blood donor samples from infection-nonreactive, 18- to 45-year-old, male, first-time blood donors in 6 US locations were tested for emtricitabine and tenofovir. Third, in men who have sex with men (MSM) participating in the 2017 Centers for Disease Control and Prevention National HIV Behavioral Surveillance (NHBS) from 5 US cities, self-reported PrEP use proximate to donation was assessed. In blind testing, no ART was detected in 300 infection-nonreactive donor samples, but in 299 HIV confirmed-infected donor samples, 46 (15.4%; 95% confidence interval [CI], 11.5% to 20.0%) had evidence of ART. Of the 1494 samples tested from first-time male donors, 9 (0.6%; 95% CI, 0.03% to 1.1%) had tenofovir and emtricitabine. In the NHBS MSM survey, 27 of 591 respondents (4.8%; 95% CI, 3.2% to 6.9%) reported donating blood in 2016 or 2017 and PrEP use within the same time frame as blood donation. Persons who are HIV positive and taking ART and persons taking PrEP to prevent HIV infection are donating blood. Both situations could lead to increased risk of HIV transfusion transmission if blood screening assays are unable to detect HIV in donations from infected donors.

Human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells was previously associated with neuropsychological function. By including individuals encompassing the full range of HIV-1-associated neurocognitive disorders, this study reports results from subjects with normal cognition, minor cognitive motor disorder, and HIV-1-associated dementia. Individuals with normal cognition had relatively low HIV DNA levels compared to those with minor cognitive motor disorder and HIV-1-associated dementia. Neuropsychological deficits were significantly associated with entry HIV DNA in all domains. These findings demonstrate for the first time that the severity of HIV-1-associated neurocognitive disorders is proportional to the amount of circulating HIV DNA.

The phenotype of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in the developed world has changed with the broad institution of highly active antiretroviral therapy (HAART) and with aging of the HIV+ population. Extrapyramidal motor signs were a prominent feature of HAND as defined in the early stages of the epidemic but has not been reevaluated in the era of HAART. Moreover, the contribution of aging to extrapyramidal motor signs in the context of HIV remains undefined. We examined these questions among the 229 HIV+ participants in the Hawaii Aging with HIV Cohort compared to age-, gender-, and ethnicity-matched HIV-negative controls. Extrapyramidal motor signs were quantified using the motor exam of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) and compared to concurrent neuropsychological and clinical cognitive diagnostic categorization. The mean UPDRSmotor score increased with older age (1.68 versus 3.35; P<.001) and with HIV status (1.18 versus 3.56; P<.001). Age group (P=.024), HIV status (P<.001), and the interaction between age and HIV (P=.026) were significantly associated with UPDRSmotor score. Among HIV+ patients, the mean UPDRSmotor score increased with worsening cognitive diagnostic category (P<.001) where it was 2.06 (2.31) in normal cognition (n=110), 3.21 (3.48) in minor cognitive motor disorder (MCMD) (n=84), and 5.72 (5.01) in HIV-associated dementia (HAD) (n=37). We conclude that extrapyramidal motor signs are increased in HIV in the era of HAART and that the impact of HIV on extrapyramidal motor signs is exacerbated by aging. These results highlight the importance of a careful neurological examination in the evaluation of HIV patients.

Macrocytosis has been increasingly observed in HIV-infected population and is an early indicator of bone marrow toxicity. A retrospective study was conducted among these patients in a HIV clinic to assess risk factors of macrocytosis. We found that lamivudine was strongly associated with macrocytosis (OR = 24.6 [2.9-3223.0], P = 0.001). This association may be due to lamivudine's effect on erythrocyte synthesis.

Objective: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk., Design: Cross-sectional analysis within the Hawaii Aging With HIV Cohort., Methods: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses., Results: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores., Conclusions: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

Low CD4 lymphocyte count was a marker for neurological disease in human immunodeficiency virus type 1 (HIV-1); but is now less common among patients with access to highly active antiretroviral therapy. In this study, the authors determine the reliability of self-reported CD4 nadir and its predictive value for neurological status. The authors identify a high degree of reliability (r = .90). After adjusting for age, current CD4 count, and duration of HIV-1, CD4 nadir relates to a current diagnosis of HIV-associated dimentia (HAD) (odds ratio [OR]: 1.395 (1.106-1.761), P = .005) and distal symmetric polyneuropathy (DSPN) (OR: 1.479 (1.221-1.769, P < .001).

Human immunodeficiency virus (HIV) infection in peripheral blood mononuclear cells (PBMCs) might be influencing the development of wasting in the era of potent antiretroviral therapy. In a retrospective study of 57 subjects, HIV proviral DNA levels in PBMCs were higher in subjects whose body weight decreased by >5% one year after initiation of highly active antiretroviral therapy, compared with subjects whose body weight was stable or increased (median HIV proviral DNA load, 8.9 vs. 0.9 copies/10(6) PBMCs; P = .006).

Objectives: Metabolic complications have been associated with HIV-1 infection and with long-term use of antiretroviral (ARV) medications. In some studies, such complications have been linked to cardiovascular events, yet limited data exist concerning metabolic complications and dementia. The objective of this study was to examine the relationship between HIV-associated dementia (HAD) and diabetes among patients with HIV-1 infection., Design: Cross-sectional analysis of entry data for a longitudinal cohort study., Methods: A total of 203 participants who were enrolled in the Hawaii Aging with HIV Cohort between October 2001 and November 2003 served as the study population. Research case definitions of HAD were determined in consensus conferences by a panel that included neurologists, neuropsychologists, and a geriatrician. Diabetes was determined by self-report or a fasting glucose level > 125 mg/dL., Results: Participants' ages ranged between 20-76 years at enrollment with approximately one-half aged >/=50 years. After adjustment for important covariates including age, education, ethnicity, CD4 lymphocyte count, duration of HIV infection, and protease inhibitor-based ARV therapy, we found a statistically significant association of diabetes with HAD (odds ratio 5.43, 1.66-17.70). A significant association remained after adjustment for other vascular risk factors. Among participants without diabetes, fasting glucose levels were higher with increasing impairment category., Conclusions: Within the Hawaii Aging with HIV Cohort, a longitudinal study enriched with older HIV-1-infected individuals, diabetes is associated with prevalent dementia. This finding is not fully explained by age or coexisting vascular risk factors. Evaluation of underlying mechanisms is warranted.

Our objectives were to understand patient demographic profiles, experiences of care and opinions about services. A questionnaire survey of 202 HIV patients and 389 genitourinary medicine (GUM) outpatients attending clinics during one week in 1999 was undertaken at a clinical directorate of HIV/GUM in west London. HIV and GUM patients differed by age (over 30: 84% vs 39%), sex (male: 88% vs 51%), and attendance (attended 6+ times: 55% vs 14%). Most indicated that they were satisfied with the general standard of care (97% HIV patients vs 95% GUM patients). Several clinic features were rated essential. When indicating reasons they might leave in the future, HIV patients were more likely to select leading edge care factors, such as lack of up-to-date treatment (54%). More GUM patients selected factors relating to convenience, such as waiting times (58%). In conclusion, most HIV and GUM patients were satisfied with their care, but differing experiences and opinions need to be addressed when planning services.

Background: The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections., Study Design and Methods: Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups., Results: The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti-HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti-HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9-24.3%) and 0 percent (95% CI: 0.0-28.3%), respectively. It was estimated that for each HIV-infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc., Conclusion: Although anti-HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.

Background: Follow-up studies from the mid-1980s showed that 1 to 5 percent of blood donors testing reactive in anti-human immunodeficiency virus type 1 (HIV-1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV-1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti-HIV-1/HIV type 2 (HIV-2) EIA-reactive, Western blot-indeterminate donors., Study Design and Methods: Donations (n = 607) with indeterminate HIV supplemental test results were identified by screening 3,021,342 donations given from November 1990 through August 1993 at five participating blood centers. Consenting donors were enrolled and samples taken 4 to 8 weeks after donation. Follow-up sera were tested by EIA and Western blot for anti-HIV-1 seroconversion and by type-specific peptide assays for antibodies to HIV-2 and HIV-1 subtype O. Peripheral blood mononuclear cells and/or plasma from the follow-up samples were tested for HIV-1 DNA and/or RNA by polymerase chain reaction. The rate of HIV-1 infection among Western blot-indeterminate donors was also estimated by multiplying the incidence rate of HIV-1 seroconversion in this donor population by the estimated duration of the EIA-reactive and Western blot-indeterminate window during seroconversion (8.5 days)., Results: Supplemental test-indeterminate donors (n = 355) enrolled a median of 38 days after donation; 265 (75%) of these donors were identified as indeterminate after an anti-HIV-1/2 EIA-reactive donation. Enrolled and non-enrolled donors had similar distributions of demographic characteristics and band patterns. Follow-up samples from all 355 donors tested negative for HIV-1 in polymerase chain reaction. Follow-up sera tested Western blot-negative in 54 cases (15%) and Western blot-indeterminate in 299 (84%). Two follow-up sera (0.6%) were interpreted, according to manufacturer's package insert criteria, as Western blot positive with p24 and gp41 bands and/or gp120/160 bands; however, paired testing of index and follow-up sera from these two cases showed identical Western blot and EIA reactivity, and polymerase chain reaction was negative for HIV RNA and DNA, which ruled out HIV infection. The absence of HIV infection in 355 Western blot-indeterminate donors was consistent with our incidence-based model analysis, which yielded an estimate of one HIV-1 infection for every 215 Western blot-indeterminate donations (95% CI, 1/39-1/8333)., Conclusion: Contemporary blood donors classified as indeterminate in supplemental HIV testing are infrequently infected with HIV. Donors whose follow-up samples test negative in anti-HIV-1/2 EIAs and negative or persistently indeterminate in Western blots should be considered eligible for reinstatement.

This article reviews the history, classification, and disease associations of the known human retroviruses and outlines their profound effects on the practice of transfusion medicine. The immunodeficiency viruses, HIV-1 and HIV-2, produce a cytolytic effect on infected lymphocytes, and are the causative agents of AIDS. In contrast are the oncoviruses, including HTLV-I and HTLV-II, which are typically lymphoproliferative and able to induce cellular transformation. Human foamy viruses, more recently recognized as a potential human neuropathogen, resemble the other retroviruses with their complex genome organization and structure.

Relationships among four serologic activation markers and T cell subsets were measured in HIV-seropositive former blood donors (N = 64) and seronegative controls (N = 61). Significant correlations were observed for the HIV group in pairwise comparisons of soluble IL-2 receptor (sIL-2R), beta 2-microglobulin (beta 2M), neopterin (NEOP), and soluble CD8 (sCD8). CD4 cell levels (number/microliter) in the HIV group showed significant negative correlation with all four serologic markers; CD8 cell levels, in contrast, showed no significant correlation with any serologic activation marker measured. Significant correlations were observed, however, among various cell surface activation markers and serologic activation markers. Specifically, the proportion of CD8 cells expressing CD45RA showed significant negative correlations with NEOP and B2M levels, whereas the proportion of CD8 cells expressing HLA-DR showed significant positive correlations with B2M and sIL-2R levels. Further, the proportion of CD8 cells expressing CD38 showed significant positive correlations with all four serologic activation markers. These findings indicate that sIL-2R, B2M, NEOP, and sCD8 show similar quantitative changes and correlational relationships to CD4 cell destruction in HIV infection; they differ, however, in their relationships to proportional changes in activated CD8 cell subsets.