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Acyclovir use and survival among human immunodeficiency virus-infected patients with CD4 cell counts of < 500/mm3. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

To examine the relationship between acyclovir use and survival in AIDS, we performed a retrospective analysis of data collected through an observational cohort of the 17-site Community Program for Clinical Research on AIDS (CPCRA), under the sponsorship of the National Institute of Allergy and Infectious Diseases. Data were analyzed regarding 2,368 patients with CD4+ lymphocyte counts of < 500/mm3, and 7,836 follow-up visits were conducted from September 1990 to July 1994. Factors associated with use of acyclovir were studied by stratified analysis of variance and Mantel-Haenzel chi 2 tests. The association between acyclovir and survival was studied with use of the proportional hazards regression model. Individuals reporting acyclovir use were more likely to be white, male, and homosexual; to have a history of herpes simplex and zoster; and to have lower CD4+ T cell counts than those who did not. After adjustments for differences in baseline factors, acyclovir use was not associated with prolonged survival.

Acyclovir↗

Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study.

CONTEXT: The impact of depression on morbidity and mortality among women with human immunodeficiency virus (HIV) has not been examined despite the fact that women with HIV have substantially higher rates of depression than their male counterparts. OBJECTIVE: To determine the association of depressive symptoms with HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV. DESIGN: The HIV Epidemiologic Research Study, a prospective, longitudinal cohort study conducted from April 1993 through January 1995, with follow-up through March 2000. SETTING: Four academic medical centers in Baltimore, Md; Bronx, NY; Providence, RI; and Detroit, Mich. PARTICIPANTS: A total of 765 HIV-seropositive women aged 16 to 55 years. MAIN OUTCOME MEASURES: HIV-related mortality and CD4 cell count slope decline over a maximum of 7 years, compared among women with limited or no depressive symptoms, intermittent depressive symptoms, or chronic depressive symptoms, as measured using the self-report Center for Epidemiologic Studies Depression Scale. RESULTS: In multivariate analyses controlling for clinical, treatment, and other factors, women with chronic depressive symptoms were 2 times more likely to die than women with limited or no depressive symptoms (relative risk [RR], 2.0; 95% confidence interval [CI], 1.0-3.8). Among women with CD4 cell counts of less than 200 x 10(6)/L, HIV-related mortality rates were 54% for those with chronic depressive symptoms (RR, 4.3; 95% CI, 1.6-11.6) and 48% for those with intermittent depressive symptoms (RR, 3.5; 95% CI, 1.1-10.5) compared with 21% for those with limited or no depressive symptoms. Chronic depressive symptoms were also associated with significantly greater decline in CD4 cell counts after controlling for other variables in the model, especially among women with baseline CD4 cell counts of less than 500 x 10(6)/L and baseline viral load greater than 10 000 copies/microL. CONCLUSIONS: Our results indicate that depressive symptoms among women with HIV are associated with HIV disease progression, controlling for clinical, substance use, and sociodemographic characteristics. These results highlight the importance of adequate diagnosis and treatment of depression among women with HIV. Further research is needed to determine if treatment of depression can not only enhance the mental health of women with HIV but also impede disease progression and mortality.

Adolescent↗

Asymptomatic oral carriage of Candida species in HIV-infected patients in the highly active antiretroviral therapy era.

Oropharyngeal candidiasis is the most common opportunistic fungal infection in individuals infected with human immunodeficiency virus. CD4+ lymphocytes count and the quantification of viral RNA in blood plasma have been found to be the main markers of HIV disease progression. The present study was conducted to evaluate Candida sp. diversity in the oral cavity of HIV-infected patients and to determine whether there was association of CD4+ cell count and viral load with asymptomatic oral Candida carriage. Out of 99 HIV-positive patients studied, 62 (62.6%) had positive culture for Candida (oral carriage) and 37 patients (37.4%) had Candida negative culture (no oral carriage). The etiologic agents most common were C. albicans and C. tropicalis. The range of CD4+ was 6-2305 cells/mm3 in colonized patients and 3-839 cells/mm3 for non-colonized patients, while the viral load was 60-90016 copies/mL for colonized patients and 75-110488 copies/mL for non colonized patients. The viral load was undetectable in 15 colonized patients and in 12 non colonized patients. Our results showed that there was no significant difference of the variables CD4+ cell count and viral load between oral candida carriage and no oral candida carriage patients.

Adolescent↗

[Effect of duration and temperature of sample preservation on the result of peripheral blood CD4+ and CD8+ T lymphocyte count in HIV/AIDS patients].

BACKGROUND: By analyzing the CD4+ and CD8+ T lymphocyte count of whole blood from HIV/AIDS patients, which were stored at different temperatures for various durations, the authors studied the ideal preserving condition for whole blood and processed, in a purpose of guaranteeing the accuracy of clinical testing of CD4+ and CD8+ T lymphocyte count. METHODS: Blood from 34 HIV carriers/AIDS patients, were kept at 4 degrees C for 2, 24, 48, or 72 h, and tested for CD4+ and CD8+ T lymphocyte count using cytometric analysis. Part of the blood was processed, and kept at degrees C or room temperature for 2, 24, 48, or 72 h, then tested for CD4+ and CD8+ T lymphocyte count. The results were compared statistically in parallel. RESULTS: Whole blood and processed samples preserved at degrees C showed no statistical difference in CD4+ T lymphocyte count among different preserving durations (P greater than 0.05), but CD8+ T lymphocyte counts were significantly different at 72 h (P less than 0.05). Processed samples at 72 h were significantly different in CD4+ T lymphocyte count(P less than 0.05), and significantly different in CD8+ T lymphocyte count at 24 h (P less than 0.05). At room temperature, samples at different duration were not significantly different in CD4+ T lymphocyte count, but significantly different in CD8+ T lymphocyte count at 48 and 72 h (P less than 0.05). CONCLUSION: There were stable results for performing analysis of the CD4+ and CD8+ T lymphocyte count of the anticoagulated blood within 48 h. At room temperature, there were stable results for performing the analysis of CD4+ and CD8+ T lymphocyte count of processed samples within 24 h. Between 24 h and 48 h, although CD4+ count was stable, CD8+ count showed significant changes, so the ratio of CD4 to CD8 changed accordingly.

Acquired Immunodeficiency Syndrome↗

HIV-2 genetic variation and DNA load in asymptomatic carriers and AIDS cases in Guinea-Bissau.

The purpose of this study was to document which genetic subtypes of HIV-2 are present in Guinea-Bissau and to investigate whether asymptomatic HIV-2 carriers and AIDS patients carry distinct genetic variants. A secondary aim was to correlate proviral DNA load to clinical and immunologic status of the patients. Thirty-eight asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau, Guinea-Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive (CD4+) lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. As expected, patients with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers (4.6 vs. 2.0 log10 HIV-2 DNA copies/10(6) CD4+ lymphocytes). Our study indicates that the HIV-2 epidemic in Guinea-Bissau is almost exclusively caused by subtype A HIV-2 variants and that the HIV-2 infections among the asymptomatic carriers and AIDS cases included in the study do not have distinct epidemiologic histories.

Acquired Immunodeficiency Syndrome↗

Accelerated course of human immunodeficiency virus infection after tuberculosis.

To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.

AIDS-Related Opportunistic Infections↗

Disease severity and symptoms of depression in Black Americans infected with HIV.

The purpose of this study was to examine depressive symptomatology in a sample of human immunodeficiency virus (HIV) infected Black Americans and to determine the extent to which measures of HIV disease severity were associated with depressive symptoms. Seventy-nine HIV-infected Black men and women (ages 25 to 68 years) participated. Measures included the Center for Epidemiologic Studies Depression Scale (CES-D) and multiple HIV disease severity variables including CD4+ lymphocyte count, CDC HIV stage, and HIV RNA viral load. Levels of self-reported depressive symptoms were high, with 58% (n = 48/79) of study participants exhibiting elevated depressive symptoms (CES-D score of > or =16). No relationship was found between CD4+ count, CDC HIV stage, sociodemographic variables, and depressive symptoms. Viral load, however, was positively correlated with elevated depressive symptoms. Although the level of depressive symptomatology was high, only two participants were receiving antidepressant medication. This study suggests that there is a significant unmet need for identification and treatment of depressive symptoms among Blacks receiving routine care for HIV disease.

Adult↗

Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immunodeficiency virus-infected person.

Two months after starting highly active antiretroviral treatment (HAART), an individual with human immunodeficiency virus type 1 (HIV-1) infection and profound CD4+ T lymphocytopenia developed several erythematous plaques on his face, which were due to borderline tuberculoid leprosy with reversal reaction. The temporal association between the development of these lesions and changes in blood CD4+ lymphocyte count and plasma HIV-1 load observed during HAART strongly suggests that the presentation of leprosy resulted from immune reconstitution.

AIDS-Related Opportunistic Infections↗

HLA-DR expression in liver in human HIV infection.

In order to clarify the relationship between HLA-DR antigen expression in the liver and human HIV infection, we studied 66 non-autopsy specimens obtained from HIV-infected patients with and without AIDS; 33 biopsies from HIV-negative patients were considered for control purposes. All biopsies were immunohistochemically tested with monoclonal antibody TAL-1B5, reacting with the alpha-chain subunit of HLA-DR in the avidin biotin complex method. We found occasional and usually weak HLA-DR expression on hepatocytes and biliocytes. By comparison with controls, HIV-positive cases showed a significantly higher percentage of HLA-DR immunoreactivity on hepatic artery and portal vein endothelial cells. No relationship was demonstrated between HLA-DR endothelial expression and the CD4+ lymphocyte count or grade of portal/periportal inflammation in the liver. The biological significance of HLA-DR expression on intrahepatic vascular endothelial cells in HIV infection still remains to be clarified.

Adult↗

Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA study.

There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2-5.2], CD4 lymphocyte count 150/mm3 (IQR 60-274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load < 500 copies/ml. Conversely, the CD4 count halved from the baseline value in 88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable analyses, a 1 log viral load reduction was related to baseline viral load [relative hazard (RH) 1.27 per 1 log higher; P = 0.008], a previous viral load of less than 500 copies/ml (RH 1.69; P = 0.002), more recent initiation of the regimen (RH 1.36 per year more recent; P = 0.02), number of new drugs in the regimen (RH 1.20 per drug; P = 0.02), time since start of antiretroviral therapy (RH 0.94 per extra year; P = 0.035) and time spent on HAART with viral load > 1000 copies/ml (RH 0.96 per extra month; P = 0.0001). Analysis of factors associated with CD4 count decline and new AIDS disease also indicated improved outcomes in more recent times and a tendency for a better response in those starting more new drugs, but no relationship with the total number of drugs. Outcomes in people starting salvage regimens appear to depend on the number of new drugs started but not on the total number of drugs being used.

Acquired Immunodeficiency Syndrome↗

Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART.

Oral candidosis (OC) has been proposed as a clinical marker of highly active antiretroviral therapy (HAART) success or failure. The principal objective of this work was to assess whether the presence OC is associated with immunologic or virologic failure in patients with HIV/AIDS undergoing HAART. One hundred fifty-one patients with HIV/AIDS from Regional Hospital "Carlos Haya," Malaga, Spain, were examined orally. All patients had been undergoing HAART for a minimum of 6 months prior to oral examination. OC diagnosis was in accordance with World Health Organization-Centers for Disease Control (WHO-CDC) criteria. Age, gender, route of HIV infection, CD4 lymphocyte counts, and viral load were taken from the medical records. In regard to HAART response the patients were classified as: virologic- responders (viral load < 50 copies per milliliter), virologic nonresponders (viral load >50 copies per milliliter); immunologic responders (CD4 cells counts > 500 per milliliter), and immunologic nonresponders (CD4 cells counts < 500 per milliliter). Prevalence of OC was determined for each group. The presence of OC was closely related to immune failure (p 0.006; odds ratio [OR] 3.38 95% confidence interval [CI] 1.262-12.046) in patients with HIV/AIDS undergoing HAART. The probability of immune failure in the presence of OC was 91% for men who have sex with men, 95.5% for heterosexuals, and 96% for intravenous drug users. In conclusion, OC should be considered a clinical marker of immune failure in patients with HIV/AIDS undergoing HAART.

AIDS-Related Opportunistic Infections↗

Patterns of viral dynamics during primary human immunodeficiency virus type 1 infection. The Sydney Primary HIV Infection Study Group.

This study used curve-fitting techniques to detail the dynamics of human immunodeficiency virus (HIV)-1 and its relationship to circulating T lymphocyte changes in a cohort of 41 male patients (mean age 36+/-7 years) infected with HIV-1. The following characteristics of viral kinetics were obtained: virus load peak, 6. 35+/-0.71 log10 RNA copies/mL at 12.2+/-7.1 days; virus load drop from peak, 2.02+/-0.93 log10 copies/mL; viral decay rate from peak, 0.071+/-0.042 log10 RNA copies/mL/day; and steady state virus load, 4.57+/-0.68 log10 copies/mL at 135+/-81 days. Analysis of individual virus load curves revealed highly variable viral kinetics. Although these could be grouped into three distinct patterns, virus load and CD4 lymphocyte counts were similar in all patterns at 12 months, but the interval from infection to achievement of steady state virus load varied significantly.

Adult↗

Elevated plasma concentration of reduced homocysteine in patients with human immunodeficiency virus infection.

Oxidative stress has been suggested to be an important factor in the immunopathogenesis of human immunodeficiency virus (HIV) infection. Reduced plasma thiols may lead to production of reactive oxygen species, thus contributing to the oxidative stress. We quantified the total, reduced, and protein-bound forms of the thiols homocysteine, cysteine, cysteinylglycine, and methionine in plasma from 21 HIV-infected patients and 15 healthy control subjects and compared the results with clinical and immunologic indexes. The HIV-infected patients had significantly higher concentrations of reduced homocysteine in plasma compared with control subjects. No significant differences in reduced homocysteine concentrations were noted when asymptomatic and symptomatic HIV-infected patients were compared, and we did not find any relation between reduced homocysteine concentrations and other markers of immunodeficiency. The HIV-infected patients had normal total homocysteine concentrations. The reduced cysteinylglycine concentration tended to be elevated in the patient group. No differences between HIV-infected patients and control subjects were found for reduced or total cysteine. Compared with control subjects, the HIV-infected patients had lower concentrations of methionine in plasma, and a significant correlation was found between low concentrations of methionine and low CD4+ lymphocyte counts in blood. Elevated concentrations of reduced homocysteine could possibly contribute to formation of reactive oxygen species, leading to accelerated immunologic deterioration and increased HIV replication.

Adult↗

Cognitive performance after progression to AIDS: a longitudinal study from the Multicenter AIDS Cohort Study.

OBJECTIVE: To describe changes in cognitive functioning before and after development of an acquired immune deficiency syndrome (AIDS)-defining illness or CD4+ lymphocyte count < 200/mm3 in participants in the Multicenter AIDS Cohort Study. METHODS: The study population included participants who either were diagnosed with an AIDS-defining illness (n = 52) or had at least one measurement of CD4+ count < 200/mm3 (n = 57) and who had at least four neuropsychological (NP) evaluations, two or more before and two or more after the AIDS diagnosis. A group of subjects with clinical diagnosis of dementia (n = 29) was also included for comparison. The NP test battery included measures of attention, memory, constructional abilities, and psychomotor speed. Longitudinal data analysis, using the generalized estimating equation, was performed separately for each NP measure. Time was measured in months from the date of clinical AIDS or CD4+ < 200/mm3. RESULTS: Before AIDS< the dementia group showed significant decline (slope different from zero) only on measures of psychomotor speed. For all other measures, there was no evidence of decline in performance before AIDS for the other groups. After development of AIDS, the group with clinical AIDS showed significant decline on psychomotor speed but none on the other cognitive measures. The group with CD4+ < 200/mm3 did not show significant decline on any of the cognitive measures after AIDS. As expected, the dementia group showed significant decline on all measures. Sensory neuropathy was associated with a significant decline in performance on measures of psychomotor speed after AIDS. Antiretroviral therapy was not associated with any measurable changes in NP performance. CONCLUSION: These results are consistent with previous findings showing no significant decline in cognitive functions before AIDS, unless overt dementia is present, and no decline in immunosuppressed subjects who have had no AIDS-defining illness. By contrast, in subjects who have developed clinical AIDS, there is mild decline in fine motor skills but no significant change in other cognitive domains.

AIDS Dementia Complex↗

Coinfection with HTLV-I and HIV: increase in HTLV-I-related outcomes but not accelerated HIV disease progression?

Human T-lymphotropic virus type I (HTLV-I) and HTLV-II have been postulated to accelerate disease progression in patients coinfected with HIV. However, recent evidence suggests that HTLV-II has no effect on HIV disease progression. In addition, it has recently been reported that HIV viral load was not increased in subjects coinfected with HTLV-I, suggesting that the biologic basis for the hypothesis does not exist. Several recent studies in Brazil, however, suggest that coinfection with HTLV-I and HIV has substantial medical consequences. For example, coinfection was associated with a higher CD4 lymphocytes count following adjustment for HIV viral load or HIV clinical stage. In addition, coinfected subjects have a high prevalence of clinical significant myelopathy. The effect of other putative viruses as cofactors in HIV disease progression is also discussed.

Brazil↗

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.

Acquired Immunodeficiency Syndrome↗

The impact of age on the quality of life in persons with HIV infection.

The authors administered the Medical Outcomes Study (MOS 20) Short Form Health Survey to 369 persons with HIV disease. The MOS survey measures six domains of health: physical function, role function, social function, mental health, health perception, and pain. Additional data included sociodemographics, HIV risk group, time since HIV diagnosis, symptoms (dyspnea, diarrhea, fever, chills, sweats, weight loss, weakness, numbness, memory trouble, seizures), and CD4 lymphocyte count within 3 months of the MOS survey. Bivariate analyses revealed worse MOS scores associated with older age in five health domains: physical function (p less than .01), health perception (p <.10), role function (n.s.), social function (n.s.), and mental health (n.s.). Older subjects reported less pain. When controlling for CD4 count and for sociodemographic and clinical variables, older age was significantly (p less than .05) associated with worse MOS scores in physical function, social function, and health perception, nonsignificantly associated with worse MOS scores in role function and mental health, and nonsignificantly associated with less reporting of pain.

Adolescent↗

The natural history of progressive multifocal leukoencephalopathy in patients with AIDS. Canadian PML Study Group.

Progressive multifocal leukoencephalopathy (PML) is usually a fatal neurological disease. The natural history of PML in patients with human immunodeficiency virus infection was analyzed. The correlations between CD4+ lymphocyte count, previous diagnosis of AIDS, treatment with cytarabine, and survival time are reported for 28 individuals for whom the diagnosis of PML was confirmed by histopathologic examination. For 16 patients (57%), PML was the AIDS-defining illness. For these 16 patients, the mean (+/- SD) survival time after presentation was 7.5 +/- 7.6 months (range, 1-31 months), whereas that for the 12 patients (43%) for whom AIDS was previously diagnosed was 3.2 +/- 2.8 months (range, 1-11 months) (P = .01). The overall mean (+/- SD) CD4+ cell count was 85 +/- 82/mm3 (range, 12-349/mm3). The mean (+/- SD) survival time for patients with CD4+ cell counts of > or = 90/mm3 at the time of presentation was 9.4 +/- 8.7 months, while that for patients with CD4+ cell counts of < 90/mm3 at the time of presentation was 3.6 +/- 1.8 months (P = .03). The nine patients did not benefit from treatment with cytarabine.

Acquired Immunodeficiency Syndrome↗