Dates Of Human Immunodeficiency Virus Seroconversion Research Articles

Association of Endothelial Dysfunction and Antiretroviral Therapy in Early HIV Infection

Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular disease (CVD) events. Endothelial dysfunction (EDF) is involved in CVD pathogenesis; however, EDF onset after HIV acquisition and the potential for reversibility with antiretroviral therapy (ART) have not been evaluated to date. To evaluate endothelial function with noninvasive reactive hyperemia index (RHI) in patients with early HIV infection at baseline and after ART initiation. Cohort study in which 61 members of the United States Air Force diagnosed with HIV infection from September 1, 2015, through September 30, 2017, were evaluated for baseline EDF. Natural log-transformed RHI values (lnRHI) of less than 0.51 and at least 0.51 were defined as abnormal and normal, respectively. The RHI interval changes were evaluated in a subgroup of 40 patients. Data were analyzed from September 30, 2017, through January 30, 2018. Early HIV infection. Baseline EDF at HIV diagnosis and interval changes associated with ART initiation. The 61 patients included in the analysis were predominantly male (58 [95%]) and mostly African American (35 [57%]), with a mean (SD) age of 28.1 (6.7) years at HIV diagnosis. Median time from estimated date of HIV seroconversion to RHI assessment was 10.6 months (interquartile range [IQR], 5.1-13.2 months), and the median CD4 lymphocyte count was 552/μL (IQR, 449/μL-674/μL). Patients had a mean (SD) body mass index of 26.2 (4.0), median (IQR) low-density lipoprotein cholesterol level of 97 (80-126) mg/dL, median (IQR) total cholesterol level of 163 (146-195) mg/dL, and no diabetes diagnoses. Overall mean (SD) lnRHI was 0.70 (0.29) at HIV diagnosis. Baseline RHI was normal in 47 patients (77%; mean [SD] lnRHI, 0.82 [0.20]) and was abnormal in 14 patients (23%; mean [SD] lnRHI, 0.30 [0.18]). Age (per 10-year increase) was not associated with an abnormal lnRHI (odds ratio, 2.15; 95% CI, 0.89-5.19; P = .09). Of the 41 patients with follow-up RHI assessments, 40 started ART immediately and repeated the RHI assessments at a median (IQR) of 6.4 (6.0-7.8) months. Use of ART was associated with an overall significan increase in mean (SD) lnRHI (0.13 [0.33]; P = .02). A greater increase in mean (SD) lnRHI was associated with abnormal (n = 11) compared with normal (n = 29) lnRHI at HIV diagnosis (0.33 [0.34]; P = .01 vs 0.04 [0.30]; P = .38). Among those with abnormal baseline lnRHI, 8 (73%) showed improved endothelial function after ART. The patient who declined ART converted from having a normal lnRHI (0.60) to an abnormal lnRHI (0.11) lnRHI after 8.3 months. In this study, EDF was common in early HIV infection, with associated reversal in most patients taking ART. Results suggest that persistent EDF and CVD complications may be associated with delayed ART. Further studies are necessary to define the role of noninvasive endothelial function testing in patients with HIV infection.

Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion

There is interest in whether a short course of combination antiretroviral therapy (cART) at the time of human immunodeficiency virus (HIV) seroconversion could induce long-term immunologic control after its interruption. We aimed to determine the time of virologic rebound after interruption of treatment initiated close to HIV seroconversion and to identify potential cases of posttreatment controllers (PTCs) in the CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) Collaboration. Prospective cohort study nested within the CASCADE database of routinely collected data about patients with HIV with well-estimated date of HIV seroconversion from Europe, Canada, and Australia in the post-cART era. Participants were individuals who interrupted successful cART initiated within 3 months of HIV seroconversion. The main outcome was loss of PTC status, defined as the earlier date of virologic rebound (first of 2 consecutive measurements showing HIV RNA levels >50 copies/mL) or reinitiation of any ART after cART interruption. Median time to loss of PTC status in 259 eligible individuals was 1.7 months. Eleven patients did not experience virologic rebound by 24 months after treatment interruption. Most patients experience virologic rebound soon after cART interruption; however, although PTCs are rare, the results of this study confirm their existence.

Preventing Deaths in Persons With HIV/Hepatitis B Virus Coinfection: A Call to Accelerate Prevention and Treatment Efforts

The prognosis associated with a new diagnosis of human immunodeficiency virus (HIV) infection has improved dramatically since the virus was first recognized [1]. However, the remarkable increases in survival have been attenuated in some groups because of the presence of comorbid infectious diseases and other illnesses. Globally, an estimated 5%–10% of the 33.3 million people living with HIV are coinfected with the hepatitis B virus (HBV). This double-whammy of HIV/HBV coinfection has translated into poorer outcomes. For instance, in settings where expanded access to antiretroviral therapy (ART) has reduced deaths from HIV, liver-related death (from any of a variety of etiologies) has emerged as an important cause for the remaining mortality [2]. Infection with HIV increases the rate of replication of HBV, thereby accelerating progression to cirrhosis, hepatocellular carcinoma, and other liver-related morbidity [3]. There is not clear evidence that HBV impacts the progression of HIV disease, but it has been speculated that HBV infection increases susceptibility to liver toxicity from ART and impairs the immunological response (eg, CD4 cell–count recovery) to HIV treatment. Evaluating whether HIV progression is an important element of the increased mortality seen in coinfected patients has been challenging because of the heterogeneity of available HIV and HBV data in studies reported to date. The report by Chun et al [4] in this issue of The Journal presents data from the U.S. Military HIV Natural History Study, which evaluates the impact of HBV coinfection on the composite endpoint of AIDS-defining illness or death. To minimize the influence of duration of HIV infection, the analysis was limited to the 2352 cohort participants whose date of HIV seroconversion could be estimated within 3 years, and whose HBV status was known or determined within 2 years of HIV seroconversion (although the timing of their HBV infection was not known). Each patient’s HBV status was classified as either chronic (hepatitis B surface antigen [HBsAg] reactivity), resolved (hepatitis B core antibody [HBcAb] and surface antibody [HBsAb] reactivity with a negative HBsAg), isolated HBcAb (HBcAb reactivity with negative HBsAb and HBsAg), or no evidence of past or current infection (negative HBcAb and HBsAg). Patients classified as having chronic HBV were observed to have a higher risk (approximately double the risk in adjusted analysis) for developing the composite outcome of AIDS-defining illness or death, compared with that of patients who were HBV negative. Hepatitis C virus (HCV) infection was uncommon in this cohort (1.7% of patients had a reactive HCV antibody test), but was also associated with an increased risk of developing an AIDS-defining illness or death. Some strengths of this analysis were the focus on individuals with known dates of HIV seroconversion to minimize survivorship bias, and the classification of HBV status around the HIV seroconversion date to minimize misclassification bias. Although the findings suggest that HBV infection may impact HIV outcomes, as with any cohort study there are methodological limitations that restrict our ability to determine causality. A limitation is that HBV infection directly causes mortality, and these deaths would be counted toward the composite outcome. In both HIV-infected and -uninfected populations, HBV infection is associated with a higher risk of mortality Received 26 September 2011; accepted 26 September 2011; electronically published 5 December 2011. Correspondence: Barbara Marston, Centers for Disease Control and Prevention, 1600 Clifton Rd, Mailstop A-05, Atlanta, GA 30329 (bxm5@cdc.gov). The Journal of Infectious Diseases 2012;205:166–8 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. DOI: 10.1093/infdis/jir728

Time From Human Immunodeficiency Virus Seroconversion to Reaching CD4+ Cell Count Thresholds <200, <350, and <500 Cells/mm3: Assessment of Need Following Changes in Treatment Guidelines

Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm³ in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm³ are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count <200, <350, and <500 cells/mm³ as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion. Median (interquartile range [IQR]) follow-up for the 18495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD4+ cell count <500, <350, and <200 cells/mm(3) were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm³, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm³, respectively. These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.

The effect of aging on the incidence of Kaposi's sarcoma among HIV-positive individuals with known dates of seroconversion.

In the general population, the incidence of the most common types of cancer (i.e., carcinomas of the lung, breast, colon, stomach, prostate and bladder) increases with age among both males and females and in different geographic areas.1,2 This pattern is explained by the multistage model for carcinogenesis, which posits that cancer arises as a consequence of multiple genetic hits acquired with aging.3 Alternatively, it has been hypothesized that this age-related increase in incidence can be attributed, at least in part, to the diminishing immunologic function associated with aging. However, among persons with severe immunosuppression, such as those who are iatrogenically immunosuppressed after organ transplantation or persons infected with the human immunodeficiency virus (HIV), the incidence of the most common types of cancer is no higher than that among immunocompetent persons. By contrast, the incidence of both non-Hodgkin’s lymphoma (NHL) and Kaposi’s sarcoma (KS), which are rare in immunocompetent persons younger than 40 years of age, has been reported to be quite high among persons with severe immunosuppression.4,5 KS is a mesenchymal tumor that, until the appearance of the HIV epidemic, was rare in the general population of industrialized countries; it was generally found in elderly men of Mediterranean or Eastern European origin.6 With regard to the pathogenesis of KS, an infectious agent – the human herpesvirus 8 (HHV-8)—has been isolated in all forms of the disease,7,8 and epidemiologic, serologic and molecular evidence has proved that infection with HHV-8 is necessary for the development of KS. Nonetheless, it has been difficult to determine the magnitude of the association between KS and HHV-8 infection because the currently used serologic assays are limited in terms of their sensitivity and specificity9 and because other, as yet unknown, cofactors exist that are likely to play a role in the development of KS.10,11 Given that HIV-infected individuals have been shown to live longer since highly active antiretroviral therapy (HAART) was introduced,12 it is now possible to study thoroughly the relationship among immunosuppression, aging and cancer. In a study13 that investigated whether or not aging affects the risk of developing HIV-associated KS and lung cancer, using data from the AIDS-Cancer Registry Match Study, the incidence of KS appeared to increase through 39 years of age and to decline thereafter. However, no information was available from this study on the duration of HIV infection, the level of immunosuppression or the prevalence of HHV-8 infection (i.e., the main determinant of KS8). We investigated the relationship among HIV-induced immunosuppression, aging and KS, taking into account the duration of HIV infection, the level of immunosuppression and, for a subgroup of the study population, the prevalence of HHV-8 infection. This study used data from the Italian HIV-Seroconversion Study. The Seroconversion Study, which was begun in 1987, is a prospective incident cohort study of HIV seroconverters who belong to different HIV exposure categories and for whom it is possible to estimate the date of seroconversion with a certain degree of accuracy, specifically, persons for whom the results of a negative HIV test followed by a positive test within 24 months are available; the date of seroconversion is estimated as the midpoint in time between the most recent negative HIV test result and the first positive result. A detailed description of the Seroconversion Study has been published elsewhere.14,15 Residual sera samples for detection of antibodies against HHV-8 were available for some of the individuals enrolled as of June 1996 in the Seroconversion Study. A single HHV-8 serologic measurement was performed: the median time that had elapsed from the date of HIV seroconversion to the date of HHV-8 testing was 0.7 years (interquartile range: 0.4–1.6 years). HHV-8 seropositivity was determined by HHV-8 lytic antigens, using an immunofluoroscence assay with a body cavity B-cell lymphoma cell line. A detailed description of the methodology used has been reported elsewhere.16 For the present analysis, we applied the Kaplan-Meier method and the Cox proportional hazards model.17 The date of HIV seroconversion was considered time-zero of the analyses, and KS was considered the end point. In particular, we estimated the KS-free survival time as the time that had elapsed from the date of HIV seroconversion to the date of diagnosis of KS (independently of whether or not it was the first AIDS-defining disease), or the date of death or the end of the study (i.e., December 2000). The

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group

The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Incidence and Consequences of Pregnancy in Women With Known Duration of HIV Infection

The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease.To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women.All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years.A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24).Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi's sarcoma in human immunodeficiency virus (HIV)-positive subjects with a known date of HIV seroconversion.

The presence of human herpesvirus 8 (HHV-8) DNA sequences was sought by polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 4 groups: 6 human immunodeficiency virus (HIV)-infected persons with well-defined dates of seroconversion, during the period between the diagnosis of HIV infection and the appearance of Kaposi's sarcoma (KS); 45 HIV-positive persons with no symptoms of HIV infection; 11 AIDS patients with KS; and 14 AIDS patients without KS. HHV-8 DNA PCR was positive in 3 of the 6 patients during HIV infection preceding the appearance of KS and in all but 1 of 11 AIDS patients with KS. HHV-8 DNA PCR was negative in all but 1 of the 45 HIV-positive persons with no symptoms of infection and in all but 1 AIDS patient without KS. These results indicate that HHV-8 DNA may be detected several years before the occurrence of KS in HIV-infected subjects.

Replacing time since human immunodeficiency virus infection by marker values in predicting residual time to acquired immunodeficiency syndrome diagnosis. Multicenter AIDS Cohort Study.

It is widely assumed that the time since human immunodeficiency virus (HIV) infection is an important indicator of HIV disease stage, yet for most infected individuals the date of infection is unknown. We consider whether marker values, such as CD4 lymphocyte number or percent and levels of serum beta2 microglobulin or serum neopterin, render time since infection unimportant for predicting the residual time to acquired immunodeficiency syndrome (AIDS) diagnosis. The Multicenter AIDS Cohort Study (MACS) contains a subsample of homosexual men whose date of HIV seroconversion is known within +/-6 months and who provide data for this analysis. From this subsample, we extract two overlapping data subsets. The first subset consists of 370 persons whose 3,723 study visits include complete data on the cellular markers CD4 lymphocyte number and percent for a period of 9 years. The second consists of 272 persons whose 1,593 visits include complete information on cellular markers and on the serological markers beta2-microglobulin and neopterin for a period of 5 1/2 years. We model the residual time to AIDS diagnosis with a regression model, in which cellular and serologic markers are the explanatory covariates (independent variables) and the residual time to AIDS is the responses variable (dependent variable). A robust estimate of the variance-covariance matrix corrects for the dependence of repeated measurements in the same individual. In the case of CD4 number and percent, the results indicate that time since infection is of none or at most little importance if the marker value is known, suggesting that time since infection can be adequately replaced by the combination of marker values. However, the serological markers alone do not eliminate the importance of the time since infection.

Recent Infection with Human Immunodeficiency Virus and Possible Rapid Loss of CD4 T Lymphocytes

To assess a hypothesized trend that persons recently infected with the human immunodeficiency virus (HIV) may have more rapid declines in absolute CD4 T-lymphocyte (CD4+ cell) counts than those who were HIV-infected in earlier years, sequential CD4+ cell counts in three groups who had definable dates of HIV seroconversion between 1978 and 1992 were reviewed. The CD4+ cell counts examined were from some of the longest extant studies in the United States: 100 homosexual and bisexual men engaged in ongoing observational cohort studies in San Francisco, Denver, and Chicago since 1978 (Group 1); 89 persons in South Carolina infected after 1986 (Group 2); and 155 injecting drug users participating in an observational cohort study in Baltimore since 1988 (Group 3). For all groups, individually and in the aggregate, mean CD4+ cell counts declined rapidly in the first year after HIV infection and then stabilized. However, there was no clear trend for lower (or higher) CD4+ cell counts by fixed time after HIV seroconversion among those seroconverting in recent compared with earlier calendar years. These data do not support a hypothesized trend for more rapid loss of CD4 T lymphocytes--and, by implication, more pathogenic strains of HIV-1--among persons acquiring HIV infection in recent years.

The Spectrum of Medical Conditions and Symptoms before Acquired Immunodeficiency Syndrome in Homosexual and Bisexual Men Infected with the Human Immunodeficiency Virus

The full range and occurrence of medical conditions in persons infected with human immunodeficiency virus (HIV) before they develop illnesses that define acquired immunodeficiency syndrome (AIDS) have not been systematically or completely described. In a retrospective and prospective cohort study, 1,073 homosexual and bisexual men in three US cities were interviewed and examined twice per year from January 1988 to September 1992. Study participants were from San Francisco, California (273 HIV-seropositive and 432 HIV-seronegative men), Denver, Colorado (107 positive and 129 negative men), and Chicago, Illinois (54 positive and 78 negative men). A total of 305 HIV-positive men had specifiable dates of HIV seroconversion (mean of 15.3 months between the last negative and the first positive HIV antibody test). Besides much increased incidences of thrush (incidence relative risk (IRR) = 23.3) and hairy leukoplakia (IRR = 551), the following conditions also occurred significantly more frequently in HIV-positive men than in HIV-negative men: anal herpes (incidence density (ID) = 10.7/100 person-years; IRR = 7.7); sinusitis requiring antibiotics (ID = 6.2/100 person-years; IRR = 2.1); anal warts (ID = 5.8/100 person-years; IRR = 2.7); seborrhea (ID = 3.8/100 person-years; IRR = 6.6); community-acquired pneumonia (ID = 1.4/100 person-years; IRR = 2.7); skin cancers (ID = 1.0/100 person-years; IRR = 2.2); and seizures, often apparently "breaking through" prior anticonvulsant therapy (ID = 0.8/100 person-years; IRR = 5.6). First episodes of hairy leukoplakia, thrush, and skin cancer occurred at low mean CD4 counts (mean counts were less than 350 cells/microliters) and late in HIV infection (mean times were more than 8 years after HIV seroconversion). Many medical problems, some not widely appreciated, occur in HIV-infected men before they develop AIDS-defining illnesses, signifying considerable morbidity from pre-AIDS HIV infection.

Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. National Cancer Institute Multicenter Hemophilia Cohort Study Group.

The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.

CD4 Lymphocyte Counts Within 24 Months of Human Immunodeficiency Virus Seroconversion

<h3>Background:</h3> Although CD4 lymphocytes are the primary target of the human immunodeficiency virus (HIV), few studies have evaluated CD4 cell counts in a large population of seroconverters with known dates of seroconversion. This study reports an analysis of CD4 lymphocyte counts and CD4 cells as a percentage of all lymphocytes within 24 months of estimated date of HIV seroconversion in 1046 HIV seroconverters. <h3>Methods:</h3> Study participants included all Navy and Marine Corps seroconverters (1023 men, 23 women) from 1987 through 1991 with a previous negative HIV test. CD4 lymphocyte counts and percentages were obtained for blood drawn from HIV seroconverters during initial clinical evaluations carried out at Naval Medical Centers in Bethesda, Md; Oakland, Calif; Portsmouth, Va; and San Diego, Calif. The seroconversion date was estimated as the midpoint between the last negative test date and the first positive test date. <h3>Results:</h3> Nearly 40% of seroconverters presented with initial CD4 lymphocyte counts lower than 0.50×10⁹/L (500/μL) and 3% with counts lower than 0.20×10⁹/L (200/μL). Approximately half the seroconverters presented with fewer than 29% CD4 cells, and 5% presented with fewer than 14% CD4 cells. There were no significant differences in CD4 counts according to sex, race, or estimated duration of HIV infection. <h3>Conclusions:</h3> Little difference in CD4 lymphocyte counts or percentages by duration of infection within 24 months was evident on initial clinical evaluation of HIV seroconverters. The high percentage of seroconverters presenting with low CD4 counts or percentages suggests a population of seroconverters with rapid depletion of CD4 lymphocytes following seroconversion. (Arch Intern Med. 1993;153:869-876)

CD4 lymphocyte counts within 24 months of human immunodeficiency virus seroconversion. Findings in the US Navy and Marine Corps. The Navy Retroviral Working Group

Although CD4 lymphocytes are the primary target of the human immunodeficiency virus (HIV), few studies have evaluated CD4 cell counts in a large population of seroconverters with known dates of seroconversion. This study reports an analysis of CD4 lymphocyte counts and CD4 cells as a percentage of all lymphocytes within 24 months of estimated date of HIV seroconversion in 1046 HIV seroconverters. Study participants included all Navy and Marine Corps seroconverters (1023 men, 23 women) from 1987 through 1991 with a previous negative HIV test. CD4 lymphocyte counts and percentages were obtained for blood drawn from HIV seroconverters during initial clinical evaluations carried out at Naval Medical Centers in Bethesda, Md; Oakland, Calif; Portsmouth, Va; and San Diego, Calif. The seroconversion date was estimated as the midpoint between the last negative test date and the first positive test date. Nearly 40% of seroconverters presented with initial CD4 lymphocyte counts lower than 0.50 x 10(9)/L (500/microL) and 3% with counts lower than 0.20 x 10(9)/L (200/microL). Approximately half the seroconverters presented with fewer than 29% CD4 cells, and 5% presented with fewer than 14% CD4 cells. There were no significant differences in CD4 counts according to sex, race, or estimated duration of HIV infection. Little difference in CD4 lymphocyte counts or percentages by duration of infection within 24 months was evident on initial clinical evaluation of HIV seroconverters. The high percentage of seroconverters presenting with low CD4 counts or percentages suggests a population of seroconverters with rapid depletion of CD4 lymphocytes following seroconversion.

Herpes zoster and human immunodeficiency virus infection.

The interaction of herpes zoster and the human immunodeficiency virus (HIV) was evaluated in a cohort study of 287 homosexual men with well-defined dates of HIV seroconversion and 499 HIV-seronegative homosexual men. The incidence of herpes zoster was significantly higher among HIV-seropositive men (29.4 cases/1000 person-years) than among HIV-seronegative men (2.0 cases/1000 person-years); the overall age-adjusted relative risk (RR) was 16.9 (95% confidence interval [CI], 8.7-32.6). When compared with that of age-matched population controls from 1945 to 1959, the incidence of zoster was significantly higher among seropositive men (RR, 26.7; 95% CI, 19.3-37.1) and slightly higher among seronegative men (RR, 1.85; 95% CI, 1.0-3.3); the latter may reflect increasing background rates over several decades. The risk of herpes zoster was not associated with duration of HIV infection and was not predictive of faster progression to AIDS.

Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.

Serum β 2-microglobulin and prediction of progression to AIDS in HIV infection

Identification of laboratory tests that can help predict progression to acquired immunodeficiency syndrome (AIDS) in people infected with human immunodeficiency virus (HIV) is important for clinical management and counselling. We have assessed the usefulness of CD4 lymphocyte count, serum β 2-microglobulin concentration, and the presence of p24 antigen as predictors of AIDS. We studied 214 homosexual and bisexual men with well-defined dates of HIV seroconversion. For each participant, we defined the baseline date as the earliest date before the development of AIDS on which the three laboratory tests were done. β 2-microglobulin concentration at baseline was in all analyses an independent predictor of AIDS, even after stratification by baseline CD4 count, duration of HIV infection, or use of zidovudine before or at baseline. For example, among men with at least 0·5 x 10 9/l CD4 cells who were negative for p24 antigen, the risks of AIDS at 12 months and 24 months were 1% and 5%, respectively, for those whose β 2-microglobulin concentrations were below 4·0 mg/l, compared with 17% and 27%, respectively for those with β 2-microglobulin concentrations above that cut-off point (p<0·001). Among men with an estimated duration of infection of 5 years or less, β 2-microglobulin concentration was the strongest independent predictor of AIDS. Measurement of serum β 2-microglobulin adds important prognostic information to CD4 count in determining the risk of progression to AIDS in HIV-infected subjects, including those whose CD4 cell count has not vet fallen.