Impact of tuberculosis on the course of HIV-infected patients with a high initial CD4 lymphocyte count.

OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of human immunodeficiency virus (HIV) infection in patients without immunological impairment. MATERIAL AND METHODS: In an observational study of retrospective cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB. Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l) and date of starting follow-up (+/-6 months). The progression of HIV infection was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200 x 10(6)/l; 2) clinical progression: time to development of acquired immune-deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease progression: time to the first defined event in 1, 2 and/or 3. The times to these events were estimated using Kaplan Meier curves. RESULTS: There were no significant differences between the cohorts for age, sex and risk group. Faster immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53-9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09; P < 0.01) were found in the cohort of TB patients. These associations were still significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x 10(6)/l) was related to greater progression to AIDS and shorter survival.     

Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations.

OBJECTIVE: To evaluate the proposed WHO/UNAIDS criteria for initiating co-trimoxazole prophylaxis in adult HIV-infected patients in Africa [WHO clinical stages 2--4 or CD4 count < 500 x 10(6) /l or total lymphocyte count (TLC) equivalent]. DESIGN: Observational cohort study of 5-year follow-up. SETTING: Adult HIV clinics, University of Cape Town, South Africa. METHODS: Effect of prophylactic low dose co-trimoxazole (480 mg per day or 960 mg three times per week) on survival and morbidity was assessed in patients stratified by WHO clinical stage, CD4 T-lymphocyte count or TLC. Patients receiving antiretroviral therapy were excluded. RESULTS: Co-trimoxazole reduced mortality [adjusted hazard ratio (AHR), 0.56; 95% confidence interval (CI), 0.33--0.85; P > 0.001] and the incidence of severe HIV-related illnesses (AHR, 0.52; 95% CI, 0.38--0.68; P < 0.001) in patients with evidence of advanced immune suppression on clinical (WHO stages 3 and 4) or laboratory assessment (TLC < 1250 x 10(6)/l or CD4 count < 200 x 10(6)/l). No significant evidence of efficacy was found in patients with WHO stage 2 or CD4 count 200--500 x 10(6)/l/TLC 1250--2000 x 10(6)/l. If we had applied the WHO/UNAIDS recommendations 88.3% of our patients would have received co-trimoxazole prophylaxis at their initial clinic visit. CONCLUSION: Co-trimoxazole in HIV-infected adults from an area in which Pneumocystis carinii pneumonia is uncommon demonstrated a survival benefit consistent with previous randomized trials. Further studies are needed to assess the optimal time of commencement of prophylaxis, as widespread co-trimoxazole use will lead to increasing antimicrobial resistance to other major pathogens in Africa.     

A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok

OBJECTIVES: To examine the impact of high-dose multiple micronutrient supplementation on survival and disease progression among HIV-infected individuals in Thailand. DESIGN: Randomized placebo-controlled trial. METHODS: Four-hundred and eighty-one HIV-infected men and women living in and around Bangkok with CD4 cell counts in the range 50 x 10(6)- 550 x 10(6)/l were randomized to receive micronutrients or placebo for a period of 48 weeks. Trial participants were examined clinically 12-weekly and tested for CD4 cell count 24-weekly. A subset were tested for HIV plasma viral load at 48 weeks. RESULTS: Seventy-nine (16%) trial participants were lost to follow-up and 23 (5%) died. The death rate was lower in the micronutrients arm with the mortality hazard ratios [95% confidence interval (CI)] of 0.53 (0.22-1.25; P = 0.1) overall and 0.37 (0.13-1.06; P = 0.052) and 0.26 (0.07-0.97; P = 0.03) among those with CD4 cell counts < 200 x 10(6)/l and < 100 x 10(6)/l respectively. There was no impact on CD4 cell count or plasma viral load. CONCLUSIONS: Multiple micronutrient supplementation may enhance the survival of HIV-infected individuals with CD4 cell counts < 200 x 10(6)/l. This could have important public health implications in the developing world where access to antiretrovirals remains poor. The clinical findings need to be reproduced in other settings and the mechanism, which appears to be independent of change in CD4 cell count, merits further investigation.     

Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy

OBJECTIVE: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy. DESIGN: Cohort study. PARTICIPANTS: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load 1000 copies/ml. MAIN OUTCOME MEASURE: CD4 count changes. RESULTS: Among patients who maintained plasma HIV RNA levels /= 350 x 10(6)/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 x 10(6)/l, 88% achieved a CD4 cell count of >/= 200 x 10(6)/l and 59% achieved a count of >/= 350 x 10(6)/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia). CONCLUSIONS: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune system's capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.     

Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study

OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study. PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 x 10(6)/l and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0--1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.     

Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population

OBJECTIVES: To assess the mortality in a cohort of HIV-infected patients starting highly active antiretroviral therapy (HAART) compared to the mortality of the general population, focusing on the influence of the CD4 cell count at the time of starting HAART. METHODS: Patients in the HIV Cohort Study in Western Denmark starting HAART before 1 January 2002 were identified. For each patient, 100 population controls matched on age and gender were extracted from the Danish Civil Registration System. Mortality rates were compared between the two cohorts overall, and in four groups defined by baseline CD4 cell counts. RESULTS: A total of 647 HIV-infected patients and 64 700 population controls were included, accounting for 53 and 815 deaths during follow-up. In the HIV group, mortality rates were 70.0 per 1000 person-years at risk in the lowest CD4 cell group (< 50 x 10 cells/l), and 3.2 in the highest (> or = 200 x 10 cells/l). Compared with population controls, mortality rate ratios declined with increasing CD4 cell counts, being 15.3 [95% confidence interval (CI), 9.8-23.8], 8.6 (95% CI, 4.3-16.8), 5.9 (95% CI, 3.0-11.4), and 3.6 (95% CI, 2.0-6.5) in the groups with CD4 cell count < 50, 50-99, 100-199, and > or = 200 x 10 cells/l. CONCLUSION: In comparison with the general population, HIV-infected patients starting HAART with a CD4 cell count above 200 x 10 cells/l had low mortality rates that were comparable with the rates found in other chronic medical diseases. The mortality rates increased considerably when treatment was started at lower baseline CD4 cell counts.     

HIV infection in the era of highly active antiretroviral therapy: the Malaga Study

We analyse the characteristics of patients diagnosed with HIV infection in the highly active antiretroviral therapy era in the southeast of Spain. Data were collected on 470 HIV patients diagnosed between January 1997 and December 2002. The number of cases fell over recent years and HIV transmission was sexual in 70.5%. The mean CD4 lymphocyte count was 302.1 x 10(6)/L and the mean viral load 4.70 log(10). Diagnosis of HIV coincided with an AIDS-defining opportunistic illness in 30.6% of patients and a late diagnosis (CD4 < 200 x 10(6)/L) was made in 48.3% of patients. A late diagnosis was related to male gender (OR 2.50; 95% CI 1.20-5.12; P < 0.001) and AIDS case (OR 18.80; 95% CI 10.50-33.80; P < 0.00001). These results suggest that there has been a progressive reduction in new cases of HIV-infected patients, with the main route of transmission being sexual and that the diagnosis was late in almost half the patients.     

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.     

Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers

OBJECTIVE: To study the association between the clinical axis of the World Health Organization (WHO) staging system of HIV infection and disease and laboratory markers in HIV-infected Ethiopians. DESIGN: Cross-sectional study. METHODS: Clinical manifestations and stage of HIV-positive individuals participating in a cohort study of HIV infection progression, and of HIV-positive patients hospitalized with suspicion of AIDS, were compared to CD4+ T-cell count and viral load. RESULTS: Of the 86 HIV-positive participants of the cohort study, 53 (62%), 16 (19%), 16 (19%), and one (1.2%) were in stage 1, 2, 3 and 4, respectively. Minor weight loss (n = 15) and pulmonary tuberculosis (n = 9) were the most commonly diagnosed conditions among the 38 (44%) symptomatic HIV-positive individuals. Although 23 (27%) HIV-positive participants had CD4+ T-cell counts less than 200 x 10(6)/l, only one was in clinical stage 4. Among 79 hospitalized HIV-positive patients, 15 (19%) and 64 (81%) were in stage 3 and 4, respectively. The majority (83.5%) had CD4+ T-cell counts < 200 x 10(6)/l. Individuals at stage 3 had lower CD4+ T-cell counts and higher viral loads when seen in hospital as compared to cohort participants (P = 0.06 and 0.008, respectively). When grouping the two study populations, the median CD4+ T-cell count decreased (337, 262, 225, 126, and 78 x 10(6)/l, P< 0.01), and the median viral load increased (4.08, 3.89, 4.47, 5.65, and 5.65 log10 copies/ml, P < 0.01), with increasing clinical stage of HIV infection (1, 2, 3 cohort, 3 hospital, and 4, respectively). Median CD4+ T-cell counts were remarkably low in HIV-negative participants (749 x 10(6)/l), and in HIV-positive participants at stage 1 and 2 (337 and 262 x 10(6)/l, respectively). CONCLUSIONS: There was a good correlation between WHO clinical stages and biological markers. CD4+ T-cell counts were low in Ethiopians, particularly during early stages of HIV-1 infection, and preliminary reference values at different stages of HIV-1 infection were determined. In HIV-infected Ethiopians, lymphocyte counts less than 1,000 x 10(6)/l in non-hospitalized individuals, and less than 2,000 x 10(6)/l in hospitalized patients, had high positive predictive value, but low sensitivity, in identifying subjects with low CD4+ T-cell counts (< 200 x 10(6)/l) who would benefit from chemoprophylaxis of opportunistic infections. The on-going longitudinal study will be useful to confirm the prognostic value of the WHO staging system.     

HIV disease progression in a patient cohort treated via a clinical research network in a resource limited setting

OBJECTIVE: To examine HIV disease progression in a cohort of adult patients treated with antiretroviral therapy (ART) via a clinical research network in Thailand. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A cohort of 417 patients enrolled in a series of randomized ART trials, between 1996 and December 2002. MAIN OUTCOME MEASURES: Progression to combined endpoint of AIDS defining illness or death according to baseline characteristics, ART used, immunological and virological responses to initial 6 months of ART. RESULTS: During 1677 person years of follow-up, 29 of 417 patients progressed; tuberculosis was the most common event defining progression (14 of 29 events). The rates of progression to combined endpoint or death alone were 1.7 [95% confidence interval (CI), 1.1-2.4] and 0.7 (95% CI, 0.3-1.3) per 10 person years respectively. Compared to patients with baseline CD4 cell counts > or =350 x 10/l, the adjusted hazard ratio (HR) for progression was 3.67 (95% CI, 1.31-10.27) for patients with <200 x 10 cells/l. Responses to 6 months of therapy were the strongest predictors of disease progression; compared to patients with undetectable viral load at 6 months, HR for progression was 4.95 (95% CI, 2.14-11.46) for viral load >4 log10. Compared to patients with a 6-month CD4 cell count > or =350 x 10/l, HR for progression was 5.22 (95% CI, 1.90-14.37) for patients with <200 x 10 cells/l. CONCLUSIONS: HIV-infected patients in Thailand who had access to ART, appropriate care, CD4 cell and viral load monitoring facilities via a clinical research network had progression rates comparable to those in developed countries. In this setting, ART initiation could generally be delayed until the CD4 cell count approaches 200 x 10/l.     

The spectrum of HIV-1-related disease among outpatients in New York City.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.     

Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDS-associated Kaposi's sarcoma

OBJECTIVE: To identify immunologic and virologic predictors of AIDS-associated Kaposi's sarcoma (KS). DESIGN: Nested case-control analysis of KS risk in a cohort of 132 HIV-infected homosexual men in New York and Washington, DC, USA. METHODS: For each KS case, we selected two HIV-infected controls, matched for CD4 cell count and Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8; KSHV) serostatus (enzyme immunoassay for antibody to KSHV protein K8.1). Cell-associated KSHV and Epstein-Barr virus (EBV) viral loads were measured with quantitative real-time PCR assays on samples collected 1 year (median) before KS diagnosis. RESULTS: Thirty-one men developed AIDS-associated KS (incidence 3.1 per 100 person years). Among HIV-infected men, KS incidence was higher among those with K8.1 seropositivity (5.0 versus 1.4 per 100 person years; P = 0.004), low CD4 cell count [hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.24-1.79 per 100 x 10(6) cells/l decline), or high HIV RNA level (HR, 3.96; 95% CI, 2.19-7.16 per log(10)). In the case-control analysis, nine of 70 evaluated subjects had KSHV viremia, generally low level (median viral load 180 copies per 1 x 10(6) cells). KSHV viremia was associated with increased KS risk (unadjusted odds ratio, 9.1; 95% CI, 1.7-48; odds ratio, 11.7; 95% CI, 1.8-76 after adjustment for K8.1 serostatus, CD4 cell count, and HIV RNA). Among K8.1-seropositive subjects, KS incidence was tenfold higher in those with KSHV viremia (30.3 per 100 person years versus 3.4 per 100 person years in those without viremia). Also, EBV viral loads were higher in cases than in controls (P = 0.07). CONCLUSIONS: Among individuals with HIV-KSHV coinfection, KSHV viremia identifies a subgroup with extremely high risk for developing KS.     

HIV-seropositive thrombocytopenia: the action of zidovudine.

The action of zidovudine when administered to individuals with severe HIV thrombocytopenia was investigated. Four individuals with platelets less than 50 x 10(9)/l and CD4 cells greater than 200 x 10(6)/l were treated with 600 mg zidovudine per day for 6 weeks, no drug for 6 weeks, 1200 mg zidovudine per day for 6 weeks, then no drug for 6 weeks. Glycocalicin, a platelet protein which correlates inversely with platelet survival, was assayed before and after treatment. Glycocalicin indices were also measured in four additional individuals with HIV thrombocytopenia. Platelet counts rose 2.5-fold [95% confidence interval (Cl), 2.0-3.0)] for four subjects who received 600 mg zidovudine per day and 4.9-fold (95% Cl, 4.0-5.8) for three subjects receiving 1200 mg zidovudine per day. Platelet counts declined during drug-free intervals. Plasma glycocalicin indices were elevated in all with untreated HIV thrombocytopenia. Indices fell after zidovudine treatment in six of seven individuals, suggesting that zidovudine prolonged platelet survival. Analysis of 170 HIV-seropositive asymptomatic individuals [mean CD4 count 474 x x 10(6)/l, standard deviation (s.d.) 245 x 10(6)/l] revealed that 14 (8%) had less than 125 x 10(9)/l platelets but only 2 (1%) had less than 50 x 10(9)/l platelets. Platelet counts increased spontaneously in eight individuals with mild HIV thrombocytopenia among the 10 for whom repeat counts were available.     

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study

OBJECTIVES: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. DESIGN: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count. RESULTS: After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l. CONCLUSIONS: There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.     

Cytomegalovirus seroconversion as a cofactor for progression to AIDS

OBJECTIVE: To study the impact of cytomegalovirus (CMV) seroconversion on HIV-1 disease progression. DESIGN: Follow-up of CMV-seronegative subjects enrolled in the French SEROCO/HEMOCO cohorts of HIV-infected subjects. METHODS: A total of 290 subjects were CMV-seronegative at enrolment in the cohort. Serological testing for CMV infection was done at enrolment and then every 6 months in CMV-seronegative subjects. The person-years method was used to calculate the incidence of CMV seroconversion. After adjustment for age, the CD4+ cell count at enrolment and the HIV exposure group in a Cox model, we studied CMV seroconversion as a time-dependent variable in progression to a CD4+ cell count below 200 x 10(6) cells/l and to clinical AIDS. RESULTS: Overall, 61 CMV seroconversions were observed. The overall incidence rate was 4.4 per 100 person-years [95% confidence interval (CI), 3.3-5.5]. The risk of progression to a CD4+ cell count below 200 x 10(6) cells/l was not increased in CMV seroconverters. However, the risk of progression to AIDS was increased two-fold in CMV seroconverters compared with subjects who remained CMV-seronegative [relative risk (RR) = 2.09; 95% CI, 1.16-3.74; P = 0.01]. CONCLUSION: This analysis of 61 CMV seroconversions, the largest study in the literature, confirms the impact of recent CMV infection on progression to AIDS.     

Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals.

OBJECTIVE: To evaluate the prognostic value of an elevated CD8 lymphocyte count in the early stages of HIV infection. DESIGN: A prospective study ongoing since January 1986. METHODS: One hundred and fifty-two asymptomatic HIV-positive individuals with a CD4 lymphocyte count > 400 x 10(6)/l at enrollment were included. Disease progression was defined as a CD4 count < 200 x 10(6)/l. RESULTS: During the follow-up period, CD4 count decreased in 33 individuals; CD8 count increased to > 1500 x 10(6)/l in 38 individuals and doubled in 35. The risk of a decreasing CD4 count was estimated to be 1.7-fold higher, although not significantly so, after the elevation of the CD8 count to > 1500 x 10(6)/l than before or in the absence of such an increase. However, this predictive value disappeared when five baseline parameters found to predict the outcome (neopterin, beta 2-microglobulin, p24 antigen, anti-p18 antibody and immunoglobulin A) were adjusted. CONCLUSION: Elevated CD8 count appears to be a weak marker for disease progression.     

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.     

Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.     

CD4+ cells and CD4+ percent as risk markers for Pneumocystis carinii pneumonia (PCP): implications for primary PCP prophylaxis.

The incidence of Pneumocystis carinii pneumonia (PCP) during 2 years in HIV-infected patients with less than or equal to 100 x 10(6)/l CD4+ cells, less than or equal to 200 x 10(6)/l CD4+ cells and less than 20% CD4+ cells of total T lymphocytes were compared. The relative PCP risk in 57 patients with less than or equal to 100 CD4+ cells was more than twice higher than in 120 patients with less than or equal to 200 CD4+ cells. The latter had almost twice higher relative PCP risk than 271 patients with less than or equal to 20% CD4+ cells. Only 3/56 patients who acquired PCP had greater than 200 CD4+ cells and 15/56 patients had greater than 100 CD4+ cells. Centers for Disease Control (CDC) recommends primary PCP prophylaxis in HIV-infected patients when the number of CD4+ cells is less than 200 x 10(6)/l or when the CD4+ is less than 20. On the basis of the presented data we suggest that primary prophylaxis is considered only when CD4+ cells fall below 200 x 10(6)/l.     

Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study

Prognosis of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma has improved since the introduction of highly active antiretroviral therapy. Burkitt lymphomas (BLs) still have poor outcome in patients with bone marrow (BM) or central nervous system (CNS) involvement when treated with standard-dose chemotherapy. We have prospectively evaluated the LMB86 regimen in 63 human immunodeficiency virus (HIV)-infected patients with stage IV (BM and/or CNS involvement) BL consecutively recruited between November 1992 and January 2006. At BL diagnosis, the median CD4 cell count was 239 x 10(6)/L (range, 16-1188 x 10(6)/L). BM and CNS involvement were present in 55 (80%) and 48 (76%) patients, respectively. Forty-four patients (70%) achieved complete response. Seven treatment-related deaths occurred and all patients experienced severe BM toxicity. With a median follow-up of 66 months (range, 6-165 months), 11 patients relapsed. The estimate 2-year overall survival and disease-free survival were 47.1% (95% CI, 34-59.1) and 67.8% (95% CI, 51-80), respectively. We identified 2 poor prognosis factors: low CD4 count and ECOG more than 2. Patients with 0 or 1 factor had good outcome (2-year survival: 60%) contrasting with patients with 2 factors (2-year survival: 12%). We conclude that LMB86 regimen is highly effective in advanced HIV-related BL and should be proposed for patients with CD4 count higher than 200 x 10(6)/L or ECOG of 2 or less.