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Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer.

The effects of locoregional postoperative radiation therapy (60 Gy on average) on cellular immunity were investigated in 11 patients with squamocellular carcinomas of the oral cavity, pharynx, or larynx. During radiation treatment, the total lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also decreased significantly. Not only the lymphocyte counts but also the in vitro lymphocyte stimulation responses to several mitogens decreased, with reductions averaging 10% to 50% of normal responses by the end of radiation therapy. Within 3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency toward normalization. This study shows that postoperative locoregional radiation therapy in patients with head and neck cancer induces a severe generalized impairment of cellular immunity.

CD4 Lymphocyte Count↗

Maternal factors associated with perinatal HIV-1 transmission: the French Cohort Study: 7 years of follow-up observation. The French Pediatric HIV Infection Study Group.

A nationwide, longitudinal study of infants born to human immunodeficiency virus-seropositive mothers has been under way in France since 1986. After 7 years of follow-up observations, we will update our assessment of the transmission rate in France and analyze, on a larger number of mother-infant pairs, the influence of maternal factors. Among the 848 pairs included in this analysis, the transmission rate was 20.2 +/- 2.7%. The transmission rate has remained stable with time and was not influenced by the mode of delivery, the mode of maternal infection, or the mother's ethnic origin. It was twice as high among the breast-fed infants as among the bottle-fed infants (40 vs. 19%, p < 0.04). Two factors were identified in a multivariate analysis (that did not include lymphocyte subset counts and the mode of feeding) as being associated with an increased risk of maternofetal transmission: p24 antigenemia (odds ratio = 3.1, confidence interval, = 1.5-6.2; p < 0.003) and elevated maternal age (p < 0.05). In the subgroup of 277 women whose absolute CD4+ lymphocyte counts at the time of delivery were available, the risk of transmission increased gradually from 15% of counts of > 600 CD4+ cells to 43% at counts of < 200. The risk of transmission was also related to the percentage of CD8+ cells, but each of the two factors seemed to play an independent role: the risk was lowest (12%) when the CD4+ cell count was > 500 and the proportion of CD8+ cells was < or = 40%, and was highest (50%) for values < 200 and > 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nevirapine versus efavirenz in 742 patients: no link of liver toxicity with female sex, and a baseline CD4 cell count greater than 250 cells/microl.

Recent studies have reported increased nevirapine hepatotoxicity in female patients with CD4 lymphocyte counts greater than 250 cells/microl (especially pregnant women). However, our open-label comparison of 742 patients treated with either nevirapine or efavirenz-based HAART as naive patients, experienced subjects, or patients on salvage therapy, found no increased hepatotoxicity in nevirapine-treated subjects, in particular with regard to both sex (females versus males) and T-cell-mediated immunodeficiency (CD4 cell counts above versus below 250 cells/microl).

Alkynes↗

Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden and mononuclear cell apoptosis.

BACKGROUND: Pathogen-negative diarrhea is common in HIV infection and has been associated with clinical symptoms, histopathology, HIV expression, CD4+ lymphocyte depletion, cytokine mRNA expression, and apoptosis of lamina propria mononuclear cells. OBJECTIVES AND METHODS: To examine the short-term (7-day) effects of treatment with combination antiretroviral therapies upon gastrointestinal symptoms and rectal mucosa in 15 HIV-infected subjects. RESULTS: Treatment was associated with significant decreases in the perception of abdominal bloating and cramps. Similar declines in RNA burden and rises in CD4+ lymphocyte counts were found in blood and mucosa. Treatment was also associated with a fall in the number of lamina propria mononuclear cells undergoing apoptosis by in situ labeling, a change that correlated with the change in mucosal viral burden. CONCLUSIONS: Peripheral blood and mucosal compartments are equally responsive to effective antiretroviral therapies. The detection of significant changes within 7 days of starting antiviral therapy implies that intestinal dysfunction may be a direct result of local HIV infection.

Anti-HIV Agents↗

Absolute lymphocyte count as surrogate for CD4+ cell count in monitoring response to antiretroviral therapy.

The objective of the study is to determine whether Absolute Lymphocyte Count (ALC) can serve as a surrogate for CD4 T-lymphocyte Cell Count (CCC) in HIV infected Nigerians on Lamivudine/Zidovudine anti-retroviral therapy. 32 adult Nigerians infected with HIV were recruited into the study. They were assessed clinically and categorised into three clinical stages A, B and C according to CDC criteria. They all received lamivudine 150 mg b.d and Zidovodine 300 mg b.d for six months. Blood specimens were taken on enrollment and at four weekly intervals for paired ALC and CCC determination. ANOVA statistics was used to determine whether ALC and CCC (separately) change significantly with increasing duration of therapy. Paired ALC and CCC values were tested for correlation. Sensitivity and specificity of low ALC values in predicting low CCC values were also calculated. The 32 patients comprised 18 males and 14 females aged between 16 and 49 years. The mean age (SD) was 36.1 (+/-7.85) years. The mean ALC value rose from 2485/l and 2352/microl before commencement of therapy to 3026/microl and 3151/microl four weeks after for males and females respectively. These changes were not significant, P>0.05. No further changes were noted over the next 24 weeks. However, the mean CCC values increased from 233/microl before therapy through 339/microl at four weeks, 362/microl at eight weeks to 398/micro1 at 12 weeks. It then fluctuated between 372/microl and 310/microl for the remaining part of the study. These changes were not significant: F: ratio = 1.28 (df = 6,181), P>0.05. A weak but significant positive correlation was established between ALC and CCC. Correlation coefficient was 0.25, P<0.05. The sensitivity and specificity of ALC 2000/microl as a predictor of CCC 200/microl were 57% and 72% respectively. ALC correlates weakly with CCC in patients undergoing antiretroviral therapy and it may not serve as a perfect surrogate for CCC as a monitor of immunological response to therapy.

Adolescent↗

Sézary syndrome and seronegative polyarthritis: treatment with extracorporeal photochemotherapy.

We describe a patient with therapy-resistant cutaneous T-cell lymphoma, Sézary syndrome variant, in association with concurrent polyarthritis and vitiligo, who was successfully treated with extracorporeal photochemotherapy (ECP). The combination of Sézary syndrome with seronegative rheumatoid arthritis is rare. In our patient the T-cell lymphoma was refractory to standard treatments that included psoralen-UVA, lymph node irradiation, and polychemotherapy. ECP has been shown to be effective in the treatment of selected cases of Sézary syndrome. There is a strong suggestion that ECP as a monotherapy can provide a significant benefit for other T-cell-mediated diseases including rheumatoid arthritis. In spite of a disease duration of 10 years, a very low CD8 cell count (2% of lymphocytes), a very high CD4 cell count (94%), and multiple unsuccessful chemotherapeutic trials before initiation of ECP, our patient achieved a long-lasting complete remission of both diseases with normalization of the CD4+ and CD8+ T-lymphocyte subsets. Concurrent developing vitiligo was unaffected by ECP.

Arthritis↗

Microvolume fluorimetry for the determination of absolute CD4 and CD8 lymphocyte counts in patients with HIV: a comparative evaluation.

This study compared CD4 and CD8 lymphocyte counts obtained by microvolume fluorimetry (MVF) with those derived by flow cytometry (FC). Samples from 192 patients with known or suspected HIV were analysed, and the distribution of CD4 counts for these samples ranged from 0 and 1,279/microl, with 142/192 (74%) of the samples having CD4 values of less than 400/microl. Good agreement between FC and MVF CD4 counts was found (MVF = 0.98 x FC + 7.30) although there was a minor constant inter-method bias of approximately +7 cells/microl for the MVF data. For CD8 counts there was a constant bias between the two methods of approximately +23 cells/microl for FC. Most outliers were associated with higher FC CD8 counts. Supplementary analyses showed a high level of agreement between FC and MVF methods for the CD4:CD8 ratios (MVF = 0.98 x FC). This suggests that observed discrepancies between FC and MVF methods were almost certainly a result of the influence of the absolute lymphocyte counts obtained from the haematology analyser. The results confirm that the IMAGN 2000 microvolume fluorimeter system can be used as an alternative to conventional flow cytometry for the enumeration of CD4 and CD8 counts.

CD4 Lymphocyte Count↗

Lipoprotein alterations in patients with HIV infection: relation with cellular and humoral immune markers.

In order to determine lipid abnormalities in serum in HIV-infected patients and their relation with humoral and cellular immunological changes. Ninety HIV-infected patients without acute inflammatory or malignant disease have been studied. Thirty healthy HIV-negative subjects constituted the control group. As compared with controls, patients with CD4 + lymphocytes > 400 x 10(6)/l had higher triglycerides and lower high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo)-A1. Lipoprotein comparison by groups of patients according to CD4 + cell counts showed a decrease of HDL-cholesterol in patients with CD4 + cells < or = 200 x 10(6)/l. When CD4 + lymphocyte counts were < 50 x 10(6)/l, total and very low density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol were increased and HDL and low density lipoprotein (LDL)-cholesterol and apo-A1 were decreased. Interferon (IFN)-alpha, beta2-microglobulin and tumor necrosis factor (TNF)-alpha were correlated positively with total and VLDL-triglycerides and negatively with HDL-cholesterol. In conclusion, lipoprotein changes in patients with HIV-infection are related with humoral and cellular immune markers. A decrease of HDL-cholesterol and apo-A1 and an increase of triglyceride levels could be considered as markers of disease progression.

Adult↗

Validity of existing CD4+ classification in north Indians, in predicting immune status.

BACKGROUND: The CD4 lymphocyte count had ethnic variability as observed in many studies. In populations with CD4 counts inherently lower than in the West, the Center for Disease Control and Prevention (CDC) classification system of HIV-infected individuals may not be appropriate. As there is no such criterion currently available for ethnic north Indians HIV-patients, we undertook this study to assess the applicability of the western case definition in north Indian HIV patients. METHODS: The CD4 counts of 40 normal and 376 HIV-infected north Indian adults attending to ID clinic, SS hospital, Varanasi were estimated by flowcytometry. The mean CD4 counts were estimated and compared between CDC groups A, B and C and controls. Receiver operator characteristic (ROC) curves were generated to determine the cut-off that correlated best with clinical staging for this population. RESULTS: For CDC groups A, B and C, the mean CD4 counts/mul (upper limits of the 95% CI) were 380.3, 249.2 and 120.9, while the mean CD4 levels in healthy volunteers was 818.4. CONCLUSION: The mean CD4 count among normal north Indians is significantly lower than that in the western population and parallels that of the Chinese. When categorized based on the Center for Disease Control and Prevention (CDC) classification system, the mean CD4 counts in HIV-infected individuals was lower. Categories of CD4 counts >280, 120-280 and < or =120 cells/microl correlate better with disease progression among HIV-infected individuals. A longitudinal study is required before guidelines for the India population can be devised.

Adult↗

Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection.

Dideoxynucleosides induce a dose-related toxic neuropathy; however, there is a paucity of information on whether other risk factors influence the development of neuropathy. We reviewed the records of 103 patients at an AIDS Clinical Trials Unit who were taking didanosine and/or zalcitabine to determine the risk factors for dideoxynucleoside-induced toxic neuropathy. Most were homosexual or bisexual (85%) men with a mean age of 39 years. The median CD4+ lymphocyte count was 59 cells/mm3, and 35% had a previous diagnosis of AIDS. Toxic neuropathy was more common in patients taking zalcitabine compared with those taking didanosine (14 of 51 versus seven of 55, p = 0.08). In the patients who took zalcitabine, those who had a low baseline serum cobalamin level, a history of heavy ethanol consumption, or a history of symptoms of peripheral nerve dysfunction were more likely to develop a toxic neuropathy (10 of 14 versus 12 of 37, p = 0.01). Conversely, there were no factors associated with the development of didanosine-induced toxic neuropathy. Dideoxynucleoside-induced toxic neuropathy is a common problem that can be disabling but is usually reversible. A history of symptoms of peripheral nervous system disease, heavy ethanol consumption, or a low serum cobalamin level may be useful in distinguishing patients at higher risk of developing zalcitabine-induced toxic neuropathy.

Acquired Immunodeficiency Syndrome↗

Herpes zoster ophthalmicus in patients with human immunodeficiency virus infection.

PURPOSE: To investigate the ocular complications of herpes zoster ophthalmicus in patients with human immunodeficiency virus (HIV) infection. METHODS: This was a retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San Francisco General Hospital for herpes zoster ophthalmicus from December 1985 through March 1994. RESULTS: All patients were initially treated with either intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was 48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild, and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four study patients (50%) had iritis, but only three (6%) had elevations in intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two others (4%) had zoster-associated central nervous system disease. Only two patients (4%) developed necrotizing retinitis, both in the form of the progressive outer retinal necrosis syndrome. CONCLUSIONS: Excluding the patients with retinitis and central nervous system disease, the rate of sight-threatening complications in our series was lower than expected. Almost one third of study patients had no ocular complications or only mild surface epithelial disease. Although the relatively low incidence of sight-threatening disease in our study population may have been a consequence of aggressive management with acyclovir, chronic infectious pseudodendritic keratitis, retinitis, and central nervous system disease, complications of ophthalmic zoster whose pathogenesis is largely a consequence of active viral replication, were particularly devastating and difficult to manage.

Acyclovir↗

Changes in T-lymphocyte subsets in intravenous drug users with HIV-1 infection.

OBJECTIVE: To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion. DESIGN: Cohort study with a median 18-month follow-up. SETTING: Community-based clinic established to study the natural history of HIV infection in IVDUs. SUBJECTS: Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study. OUTCOME MEASURES: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential. RESULTS: Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs. CONCLUSION: Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.

Adult↗

Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group.

The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

AIDS-Related Opportunistic Infections↗

Treatment of hepatitis C in HIV-infected patients: regularly reassess the benefits and risks.

(1) HIV-infected patients appear to be at an increased risk of complications of hepatitis C virus (HCV) infection. (2) Treatments for hepatitis C have been assessed in four open-label randomised controlled trials involving more than 1500 HIV-infected patients. Only virological endpoints were assessed. Patients with low CD4 lymphocyte counts were excluded, and few patients had cirrhosis. (3) Only one of these trials compared ribavirin versus placebo in combination with peginterferon alfa-2a. The addition of ribavirin increased the antiviral efficacy of interferon: 40% of the patients receiving ribavirin had no detectable virus at 24 weeks after the end of treatment versus 12% of patients in the placebo group. (4) The four trials compared peginterferon alfa-2 (a or b) with interferon alfa-2 (a or b) in combination with ribavirin. The results of the four trials were similar: overall, significantly more patients infected with HCV genotype 1, 2, or 3 on peginterferon alfa-2 (26-44%) than on standard interferon alfa-2 (18-21%) had no detectable virus at 24 weeks. However, treatment was more effective in patients infected with genotype 2 or 3 (44-62% of patients without detectable virus) than in patients infected with genotype 1 (17-29%). These results appear to be less favourable than those obtained in other studies of HIV-seronegative patients. (5) In the short term, virological efficacy seems to be associated with a lower frequency of histological progression, but this is based on an analysis of only half the patients enrolled in a single trial. (6) The proportion of withdrawals for adverse events with peginterferon alfa-2 + ribavirin treatment ranged from 4% to 15%, depending on the trial. (7) The CD4 cell count fell by about 140/mm3 on average during peginterferon alfa-2a + ribavirin therapy. One patient died after a particularly sharp drop. (8) Treatment of hepatitis C appears to increase the risk of lactic acidosis associated with antiretroviral drugs (especially didanosine). (9) In practice, HIV/HCV coinfected patients treated for hepatitis C must receive close clinical and laboratory monitoring, and the individual risk-benefit balance must be regularly assessed. Clinical trial data available in early 2005 do not show whether the benefits of treatment for hepatitis C outweigh the risks in patients with mild hepatic fibrosis, cirrhosis, or a low CD4 cell count.

Acidosis, Lactic↗

Correlation of clinical and laboratory surrogate markers of immunodepletion with T cell subsets (CD4 & CD8) determined flow cytometrically in HIV infected patients: a hospital based study.

CD4 count is established in HIV medicine as a marker of immune depletion. However, due to financial constraints this facility is not readily available in India. Therefore, this cross sectional study in the setting of a government hospital in Pune evaluated 72 HIV infected patients for the surrogate markers of CD4 count by correlating CD counts with clinical and easily available laboratory parameters. Using a data extraction Performa, the epidemiological and clinical data of these patients was noted. Routine hematological parameters were determined. T cell subsets were studied by 2-color flow cytometry. These included CD4 counts, CD4 percentage, CD8 counts, CD8 percentage and CD4/CD8 ratio. Status of cell-mediated immunity was determined using a Multi test CMI device and Mantoux reactivity. beta2 microglobulin levels were determined in 50 of the patients. Immunological parameters were correlated with the clinical profile and other simple laboratory markers. Statistical analysis was done using regression coefficients and paired t tests. Patients who had lesser weights had lower CD4 and CD8 counts, ALC (absolute lymphocyte counts) and CD4%. Fall in hemoglobin was associated with low CD4 count, low ALC and low CD8. ALC levels correlated well with CD4 counts below 500 cells / cmm. Patients with anergic skin response to Mantoux testing and impaired cell mediated immunity had lower CD4 counts than those who had intact cell mediated immunity. beta2 microglobulin levels did not correlate well with declining immune dysfunction. However a significant inverse correlation was established between beta2 microglobulin and CD4%.

AIDS-Related Opportunistic Infections↗

Serum beta 2-microglobulin and prediction of progression to AIDS in HIV-infected injection drug users.

Several immunological and serological variables have become established in recent studies as valuable markers to identify human immunodeficiency virus (HIV)-positive individuals at the highest risk for rapid disease progression. These studies have been performed mainly in cohorts of homosexual men. In this study, we assessed the usefulness of CD4 lymphocyte count, serum beta 2-microglobulin concentration, and the presence of p24 antigen as predictors of AIDS in a cohort of 130 HIV-positive injection drug users (IDUs) followed-up for 1 to 67 months. Progression to AIDS was most strongly associated with reduced absolute numbers of CD4+ lymphocytes at baseline, but increases in beta 2-microglobulin levels at baseline were an independent predictor of outcome. After stratification by baseline CD4 count, beta 2-microglobulin concentration added significant prognostic information to CD4 count among IDUs with > 500/mm3 CD4 cells (Breslow statistic value, 5.84, p = 0.01). Thus among seropositive IDUs with normal CD4 counts, increases in beta 2-microglobulin may be used as an early marker of individuals with higher risk of progression to AIDS, who may benefit from more intensive laboratory monitoring or clinical management.

AIDS-Related Opportunistic Infections↗

T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective therapy.

OBJECTIVE: To determine whether improved prediction of AIDS-free survival following HIV-1 seroconversion is achieved by measuring HIV-1 2-LTR episomal DNA (2-LTR) circles and T cell receptor rearrangement excision circles (TREC), reflecting HIV replication and lymphocyte emigration from the thymus, respectively. DESIGN: Subanalysis of a cohort of 154 patients with hemophilia who became HIV positive between 1978 and 1985 and were followed prospectively. METHODS: Relative hazards (RH) of AIDS, in the absence of highly effective anti-HIV therapy, were estimated for age, HIV-1 viral load, CD4 lymphocyte count and levels of HIV-1 2-LTR circles and TREC [per 106 peripheral blood mononuclear cells (PBMC)]. RESULTS: TREC correlated significantly with CD4 cell counts (r = 0.30) and age (r = -0.60). 2-LTR circles correlated significantly with HIV-1 viral load (r = 0.35). If viral load, CD4 lymphocytes and age were included in a proportional hazards model, the risk of AIDS during a median of 11.6 years of follow-up was increased significantly with fewer TREC (adjusted RH, 2.0 per log10 copies/106 PBMC) and more 2-LTR circles (RH, 1.7 per log10 copies/106 PBMC). AIDS prediction with TREC and 2-LTR circles held for most subgroups defined by median viral load, CD4 lymphocytes and age. CONCLUSIONS: PBMC that have high levels of HIV-1 replication and low levels of recent thymic emigrants are associated with a substantially increased risk of AIDS. It is not known if measurement of either TREC or 2-LTR circles will complement HIV-1 viral load as an estimation of the risk of AIDS for patients who are receiving highly effective anti-HIV therapy.

Acquired Immunodeficiency Syndrome↗

CD8+ lymphocyte counts and the risk of death in advanced HIV infection.

BACKGROUND: Mortality related to human immunodeficiency virus (HIV) infection occurs predominantly in patients with CD4+ lymphocyte counts of less than 50 cells/mm3. We followed 133 HIV-infected patients with enrollment CD4 counts of less than 50 cells/mm3 to determine if the risk of death during a 1-year period could be predicted by a single enrollment CD8+ lymphocyte count. METHODS: Enrollment data including age, sex, T-cell subset counts, p24 antigen status, antiretroviral use, and preexisting HIV-related illnesses were collected on a cohort of 133 consecutive patients with enrollment CD4 counts of less than 50 cells/mm3. The cohort was followed for 1 year, and survival data were analyzed in relation to enrollment variables. RESULTS: The mean enrollment CD8 count of those patients alive at 1 year was 600 cells/mm3, compared with a mean enrollment CD8 count of only 370 cells/mm3 in patients who had died prior to 1 year (P < .001). For every 100-cell decline in the enrollment CD8 count, the risk of death increased by 16% (95% confidence interval [CI], 5% to 22%), independent of other enrollment variables, including CD4 counts and p24 antigen status. A significant CD8 count warning level of 415 cells/mm3, irrespective of the presence of other enrollment variables, was associated with death within 1 year. The Kaplan-Meier estimated chance of death within 1 year was 54% (95% CI, 42% to 66%) for patients with CD8 counts of less than 415 cells/mm3 compared with only 25% (95% CI, 14% to 36%) for patients with CD8 counts greater than 415 cells/mm3. CONCLUSIONS: This study finds that a single CD8 count has important prognostic significance in patients with advanced HIV infection and suggests that potential therapies to enhance CD8 counts might be beneficial to patients with advanced HIV infection.

Acquired Immunodeficiency Syndrome↗