Use of CD4 lymphocyte count to predict long-term survival free of AIDS after HIV infection.

OBJECTIVE--To estimate the probability of remaining free of AIDS for up to 25 years after infection with HIV by extrapolation of changes in CD4 lymphocyte count. DESIGN--Cohort study of subjects followed from time of HIV seroconversion until 1 January 1993. Creation of model by using extrapolated linear regression slopes of CD4 count to predict development of AIDS after 1993. SETTING--Regional haemophilia centre in teaching hospital. SUBJECTS--111 men with haemophilia infected with HIV during 1979-85. Median length of follow up 10.1 years, median number of CD4 counts 17. The model was not fitted for three men because only one CD4 measurement was available. MAIN OUTCOME MEASURES--Development of AIDS. INTERVENTIONS--From 1989 prophylaxis against candida and Pneumocystis carinii pneumonia and antiretroviral drugs when CD4 count fell below 200 x 10(6)/l. RESULTS--44 men developed AIDS up to 1 January 1993. When AIDS was defined as a CD4 count of 50 x 10(6)/l the model predicted that 25% (95% confidence interval 16% to 34%) would survive for 20 years after seroconversion and 18% (11% to 25%) for 25 years. Changing the CD4 count at which AIDS was assumed to occur did not alter the results. Younger patients had a higher chance of 20 year survival than older patients (32% (12% to 52%) for those aged < 15, 26% (14% to 38%) for those aged 15-29, and 15% (0% to 31%) for those aged > or = 30). CONCLUSIONS--These results suggest that even with currently available treatment up to a quarter of patients with HIV infection will survive for 20 years after seroconversion without developing AIDS.     

HIV disease progression in 854 women and men infected through injecting drug use and heterosexual sex and followed for up to nine years from seroconversion. Italian Seroconversion Study.

OBJECTIVE--To compare the progression of HIV-1 infection in men and women followed up for up to nine years after an accurately estimated date of seroconversion. DESIGN--Prospective observational study. SETTING--16 HIV outpatient clinics across Italy. SUBJECTS--321 women and 533 men infected with HIV through injecting drug use or heterosexual sex and with accurately estimated dates of seroconversion. MAIN OUTCOME MEASURES--Progression to severe CD4 lymphocytopenia (CD4 lymphocyte count < 200 x 10(6)/l), development of AIDS defining diseases, and death from AIDS. RESULTS--Thirty two women and 67 men developed AIDS at Kaplan-Meier progression rates of 25% (95% confidence interval 13.8% to 35.5%) and 23% (15.6% to 30.4%), respectively, 7 years after seroconversion. In a Cox proportional hazards model the relative hazard was 0.93 (that is, a slightly lower hazard in women) before and 1.10 (0.70 to 1.72) after adjusting for age, HIV exposure group, and year of seroconversion. When CD4 lymphocytopenia and death from AIDS were used as end points the results were similar, with adjusted relative hazards of 0.95 (0.63 to 1.42) and 0.72 (0.48 to 1.79) respectively. In both women and men the risk of developing AIDS before the CD4 lymphocyte count had declined below 200 x 10(6)/l was small (3% in women, 6% in men). The estimated median count at which AIDS developed in women (34 x 10(6)/l; 10 x 10(6) to 44 x 10(6)) was similar to that for men (44 x 10(6)/l; 22 x 10(6) to 60 x 10(6)). CONCLUSION--There seems to be little evidence for appreciable differences in the natural course of HIV infection between men and women followed up from the time of seroconversion.     

Comparison of immunodeficiency and AIDS defining conditions in HIV negative and HIV positive men with haemophilia A.

OBJECTIVE--To investigate the hypothesis that high usage of clotting factor concentrate, rather than HIV infection, is the cause of immunodeficiency and AIDS in men with haemophilia. DESIGN--A comparison of AIDS defining conditions and CD4 counts in HIV positive and HIV negative patients with haemophilia matched for usage of clotting factor concentrate. SETTING--A comprehensive care haemophilia centre. SUBJECTS--17 HIV positive and 17 HIV negative male patients with haemophilia A (age range 12-60 at beginning of study period) who had received similar amounts of clotting factor concentrate yearly over the years 1980-90. MAIN OUTCOME MEASURES--Clinical events listed as AIDS defining in the Centers for Disease Control AIDS definition; CD4 lymphocyte counts; death. RESULTS--Of 108 HIV positive male patients with haemophilia A, only 17 could be matched to an HIV negative patient. This was due to the much higher average usage of factor VIII in the HIV positive group. Between 1980 and 1990, 16 clinical events occurred in nine of the 17 HIV positive patients. No event occurred in the 17 HIV negative patients. In each pair the mean CD4 count during follow up was, on average, 0.5 x 10(9)/l lower in the HIV positive patient. CONCLUSION--These data reject the hypothesis that high usage of clotting factor concentrate, rather than HIV infection, is the cause of immunodeficiency and AIDS in men with haemophilia.     

Characterisation of AIDS presenters and their response to antiretroviral therapy at legnano general hospital (Italy) during the period 2000-2008

The aim of this study was to characterise the AIDS presenters diagnosed between 2000 and 2008 in Legnano (Italy), and describe their initial response to highly active antiretroviral therapy (HAART) and trends over time. Seventy-six (48.7%) of 156 patients diagnosed as having AIDS in the period 2000-2008 were AIDS presenters. The proportion of AIDS presenters increased from 23.8% in 2000 to 70.6% in 2008 (p = 0.009). The major risk factors were heterosexual transmission and a foreign place of birth, and did not significantly change over time. The median CD4+ cell count at diagnosis was 30 cells/microl and the median level of HIV RNA was 5.38 log copies/ml, with no differences between the transmission risk groups. Fifteen AIDS presenters died of AIDS-defining diseases; the others started HAART (72% with 2 NRTIs + boosted PI), and 40% after a drug resistance test. The median duration of the initial HAART was 107 days. After three months, 34% of the patients had undetectable HIV-RNA levels and the median CD4+ cell count was 140 cells/microl; the corresponding figures after 12, 24 and 48 months were respectively 84%, 82.3% and 94.1%, and 310, 370 and 380 cells/microl. In conclusion, the AIDS presenters were mainly heterosexual men and immigrants. Their proportion increased significantly over time, and a substantial proportion maintained an immunovirological response to HAART.     

广西人类免疫缺陷病毒感染者/艾滋病患者合并马尔尼菲篮状菌感染的特征及Mp1p抗原快速筛检的研究

为调查广西人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者/艾滋病(acquired immunodeficiency syndrome,AIDS)患者合并马尔尼菲篮状菌(Talaromyces marneffei,TM)感染的特征并评价TM Mp1p(一种甘露糖蛋白)抗原试剂...     

Is the clinical course of HIV-1 changing? Cohort study.

OBJECTIVE: To assess whether the clinical course of HIV infection has changed from 1985 to 1995. DESIGN: Cohort Study. SETTING: Infectious disease clinic. SUBJECTS: 285 patients recruited from September 1985 to January 1995 with < or = 12 months between the dates of their last seronegative and first seropositive test result and with first follow up visit in the six months after seroconversion and at least 12 months'' follow up. Patients were grouped according to the date of seroconversion. MAIN OUTCOME MEASURES: Time to CD4 cell count of < 500, 400, and 200 x 10(6) cells/l, and clinical outcome defining AIDS; variation in cell count per day between consecutive visits, and ratio between this variation and time from estimated date of seroconversion at each visit. RESULTS: The groups were similar in age, number with acute primary HIV infection, CD4 cell count at intake, and cell count at the beginning of antiretroviral treatment; they differed in sex ratio, risk factors for HIV, probability of CD4 cell decline to < 500, 400, and 200 x 10(6) cells/l. and risk of developing AIDS. Acute infection, seroconversion after December 1989, and serum beta 2 microglobulin > 296 nmol/l were independent predictors of poor clinical course. The speed of CD4 cell decline, expressed as cell variation divided by the number of days between consecutive visits, increased with more recent seroconversion (P = 0.02). Ratio between the speed of CD4 cell decline and time from estimated date of seroconversion at each visit was also higher in the patients who seroconverted after December 1989. CONCLUSIONS: The faster disease progression and the higher speed of CD4 cell decline at early stages in the patients with recently acquired HIV infection suggest changes in the clinical course of HIV infection.     

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi''s sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.     

Distribution and Determinants of Cytomegalovirus Induced End Organ Disease/s among People Living with HIV/AIDS in a Poor Resource Setting: Observation from India

BackgroundIn India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects.MethodsIn a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008–2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR).ResultsAmong subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60–100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18–1.82) and for CD4 = 30–59: RR = 1.64 (95%CI = 1.18–2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values.ConclusionPrognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population.     

Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort

The three year actuarial progression rate to the acquired immune deficiency syndrome (AIDS) in a cohort of men in San Francisco who were seropositive for the human immuno-deficiency virus (HIV) was 22%. An additional 26 (19%) developed AIDS related conditions. β₂ Microglobulin concentration, packed cell volume, HIV p24 antigenaemia, and the proportion and number of T4 lymphocytes each independently predicted progression to AIDS. β₂ Microglobulin was the most powerful predictor. The 111 subjects tested who were normal by all predictors (40%) had a three year progression rate of 7%, and the 68 subjects who were abnormal by two or more predictors (24%) had a progression rate of 57%. Two thirds of all men who progressed to AIDS were in the last group. The median T4 lymphocyte count in subjects who did not progress to AIDS fell from 626 × 10⁶ to 327 × 10⁶/1. HIV p24 antigenaemia developed in 7% of the subjects per year. The proportion who were abnormal by two or more predictive variables rose to 41%. At three years an estimated two thirds of the seropositive subjects showed clinical AIDS, an AIDS related condition, or laboratory results that were highly predictive of AIDS.It is concluded from the observed rates and the distribution of predictive variables at three years that half of the men who were seropositive for HIV will develop AIDS by six years after the start of the study, and three quarters will develop AIDS or an AIDS related condition.     

43 例HIV/AIDS 患者抗病毒治疗情况分析

目的:研究来第四军医大学唐都医院传染科就诊的人类免疫缺陷病毒/艾滋病(Human immunodeficiency virus/Acquired immuno deficiency syndrome,HIV/AIDS)患者感染状况及抗病毒治疗效果。方法:采用前瞻性随访研究的方法,收集来我院就诊的HIV/AIDS患者的基本信息,并对其实验室检查结果、治疗方案及后续随访结果进行分析。结果:随访观察的43例HIV/AIDS患者治疗前平均基线CD4+T淋巴细胞计数为(330.74±176.35)cells/μL,CD8+T淋巴细胞计数为(1177.80±321.49)cells/μL,CD4+,CD8+T淋巴细胞比值为0.30±0.19;治疗一年后平均CD4+T淋巴细胞计数为(482.74±217.77)cells/μL,CD8+T淋巴细胞计数为(861.53±282.85)cells/μL,CD4+,CD8+T淋巴细胞比值为0.59±0.28。所有患者治疗一年后血浆HIV-RNA载量均达到检测限以下(500copies/m L)。结论:规范的抗病毒治疗对于改善HIV/AIDS患者预后至关重要;基线CD4+T淋巴细胞计数越低,抗病毒治疗效果越差。     

CD4+CD25+FoxP3+ 调节性T 细胞与黑龙江省HIV/AIDS 患者病情 相关性的研究

目的:比较黑龙江省HIV/AIDS患者与健康对照者(healthy controls,HCs)外周血CD4+CD25+FoxP3+调节性T细胞数量、免疫抑制功能的变化,探讨CD4+CD25+FoxP3+调节性T细胞在HIV/AIDS感染过程中的作用。方法:采用流式细胞仪检测21例HIV/AIDS患者及20例健康对照组的外周血CD4+CD25+FoxP3+调节性T细胞数量的百分比及绝对数量;采用共同培养方法检测HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞免疫抑制功能的变化;实时荧光定量聚合酶链反应(RT-FQ-PCR)检测HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞中FoxP3mRNA的表达。结果:黑龙江省HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞比率明显高于HCs(P<0.01),而CD4+CD25+FoxP3+调节性T细胞的绝对计数显著下降,且与CD4+T细胞绝对计数成反比;混合淋巴细胞共同培养结果显示,HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞的抑制功能无明显变化;HIV/AIDS患者外周血CD4+CD25+FoxP3+调节性T细胞的FoxP3 mRNA相对表达量无显著变化。结论:黑龙江省HIV/AIDS患者CD4+CD25+FoxP3+调节性T细胞的数量变化与病情相关。     

Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection.

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (less than 0.5 X 10(9)/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.     

Seroprevalence of Toxoplasma gondii Infection among HIV/AIDS Patients in Eastern China

Toxoplasmosis, a neglected tropical disease caused by the protozoan parasite Toxoplasma gondii, occurs throughout the world. Human T. gondii infection is asymptomatic in 80% of the population; however, the infection is life-threatening and causes substantial neurologic damage in immunocompromised patients such as HIV-infected persons. The major purpose of this study was to investigate the seroprevalence of T. gondii infection in subjects infected with HIV/AIDS in eastern China. Our findings showed 9.7% prevalence of anti-T. gondii IgG antibody in HIV/AIDS patients, which was higher than in intravenous drug users (2.2%) and healthy controls (4.7%), while no significant difference was observed in the seroprevalence of anti-Toxoplasma IgM antibody among all participants (P>0.05). Among all HIV/AIDS patients, 15 men (7.7%) and 10 women (15.9%) were positive for anti-T. gondii IgG antibody; however, no significant difference was detected in the seroprevalence of anti-Toxoplasma IgG antibody between males and females. The frequency of anti-Toxoplasma IgG antibody was 8.0%, 13.2%, 5.5%, and 0% in patients with normal immune function (CD4⁺ T-lymphocyte count ≥500 cells/ml), immunocompromised patients (cell count ≥200 and <500 cells/ml), severely immunocompromised patients (cell count ≥50 and <200 cells/ml), and advanced AIDS patients, respectively (cell count <50 cells/ml), while only 3 immunocompromised patients were positive for anti-T. gondii IgM antibody. The results indicate a high seroprevalence of T. gondii infection in HIV/AIDS patients in eastern China, and a preventive therapy for toxoplasmosis may be given to HIV/AIDS patients based on CD4⁺ T lymphocyte count.     

Clinical course of primary HIV infection: consequences for subsequent course of infection.

OBJECTIVE--To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN--Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS--86 Men in whom seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE--Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS--Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively). CONCLUSION--The course of primary infection may determine the subsequent course of the infection.     

Changes in Thyroid Function in Ethiopian and Non-Ethiopian Israeli Patients With Human Immunodeficiency Virus Infection or Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether human immunode ficiency virus (HIV) infection or its treatment is a risk fac tor for thyroid dysfunction and whether thyroid function changes over time in 2 distinct subpopulations with HIV or acquired immunodeficiency syndrome (AIDS) in Israel: Ethiopian immigrants and Israeli patients.MethodsSerum thyroid-stimulating hormone (TSH) and free thyroxine levels were determined in HIV carriers undergoing follow-up at the Hadassah-Hebrew University Medical Center HIV clinic in Jerusalem, Israel, and these thyroid measurements were correlated with clinical and laboratory variables pertaining to their disease, including disease duration, drug therapy, viral load, CD4 count, low density lipoprotein cholesterol, and creatine kinase. Serum samples stored at − 20°C from the time of referral were tested as well.ResultsWe recruited 121 consecutive patients with HIV or AIDS for this study: 60 Ethiopians and 61 Israeli patients. Of the 121 patients, 4 (3%) had abnormal thyroid function—subclinical hypothyroidism in 2, overt hypothy roidism in 1, and overt hyperthyroidism in 1. Previously stored serum samples were available for 60 of the 121 patients and revealed 2 additional patients with subclini cal hypothyroidism, whose TSH has normalized in the subsequent test. Throughout the follow-up period of 3.2 ± 1.9 years, the mean TSH level remained unchanged in the Israeli cohort but significantly declined in the Ethiopian cohort.ConclusionThyroid function abnormalities were uncommon in these Israeli patients with HIV or AIDS. This finding does not support the need for routine thyroid func tion tests in this patient population. The decline in TSH level in the Ethiopian population over time probably repre sents a shift from an iodine-deficient to an iodine-sufficient country. (Endocr Pract. 2012;18:882-886)     

HIV(+)/AIDS并发肺结核与单纯肺结核患者临床对照分析

提高对HIV(+)/AIDS并发肺结核临床表现的认识。方法:选取1998年以来我院收治的HIV(+)/AIDS并发肺结核的病例共47例为观察组(A组),及同期住院的HIV(-)单纯肺结核病例50例为对照组(B组)进行回顾性对照分析。结果:(1)A组发烧和体重下降较B组更常见,而咳嗽和咯血较B组少见;(2)A组痰抗酸杆菌阳性率显著低于B组;(3)A组结核杆菌培养阳性率显著低于B组,而耐多药结核(MDR-TB)所占比率显著高于B组;(4)肺结核的X线表现为弥漫性浸润或粟粒性阴影的,A组多于B组,而A组影像学空洞率显著低于B组;(5)A组合并肺外结核较B组多见,A组淋巴系统较B组常发生结核病变,A组全身血液播散性结核病的发病率明显高于B组;(6)PPD结核菌素反应阳性率A组显著低于B组,A组PPD阳性率与外周CD4+T淋巴细胞数相关。结论:HIV(+)/AIDS患者并发肺结核临床表现不典型。     

Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2

Human immunodeficiency virus (HIV) infection-induced apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 T cells and other types of cells is a major factor in the pathogenesis of AIDS. Clinically, HIV-2 patients have a higher CD4 cell count at the time of an AIDS diagnosis, and generally have longer survival after development of symptoms. The mortality after an AIDS diagnosis has been reported to be more influenced by CD4 cell count than HIV type. Previous studies have shown significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes; however, the relative contributions of HIV-1 and HIV-2 infection leading to cell death remain unclear. Using a human cell line, Jurkat, we examined differences in key molecules involved in apoptotic signaling pathways during infection with either HIV-1 or HIV-2. HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38α, JNK, c-Yes, total PKC, and decreased the expression of molecules such as p38β, ERK1/2, and XIAP relative to HIV-2 infection. HIV-1 induced a higher degree of cell death through stronger activation of both apoptotic pathways. HIV-1 infection downregulated both Bcl-X_L and FLIP expressions at later time points postinfection, while HIV-2 infection dramatically upregulated both Bcl-X_L and FLIP expression. We also found that the expression of Bcl-X_L or FLIP resulted in significant inhibition of HIV replication in Jurkat cells. These findings suggest that HIV-1 infection with high levels of cytotoxicity results in a higher level of cell death through apoptosis during a short time postinfection. The longer period of infection observed with HIV-2 with a lower degree of cytotoxicity was accompanied by increased Bcl-X_L and FLIP expression. High protein levels of Bcl-X_L or FLIP inhibit HIV replication and may be one explanation for the clinical observation that HIV-2 infected patients generally tend to be long-term nonprogressors with high CD4 lymphocyte counts compared with HIV-1 infected persons.     

Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies.

To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk of a worsened clinical condition was 55 times higher in seropositive men whose responses to pokeweed mitogen were low than in other seropositive men. The corresponding relative risks for low transformation responses to cytomegalovirus and for a decreased absolute count of CD4 positive lymphocytes were 18 and six. The relative response to pokeweed mitogen is therefore a very sensitive short term predictive marker of the clinical condition of seropositive patients who have a CD4:CD8 ratio of less than 1.0.