HIV/HTLV-II coinfection and CD4+ cell count controlling for plasma HIV viral load in injection drug users in Baltimore

The private sector, and drug companies in particular, are beginning to play a much stronger and visible role in funding health care research in canada. The implications of this change were discussed at a recent conference.     

Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements

OBJECTIVE: To evaluate the prognostic significance for AIDS occurrence of plasma levels of immune activation markers in comparison with and in conjunction with HIV viral load and CD4 T-cell measurements. DESIGN: A retrospective analysis was conducted of three plasma activation markers, the soluble tumor necrosis factor (TNF) receptor II (TNF-RII), neopterin and soluble interleukin-2 receptor levels, and of CD4 T-cell levels and plasma HIV viral load. SUBJECTS: The participants were 659 men taking part in the University of California Los Angeles Multicenter AIDS Cohort Study who were HIV-seropositive but AIDS-free in 1985. MAIN OUTCOME MEASURE: Clinically defined AIDS within 3 years. Failure time statistical regression models for the time to development of AIDS were used to assess prognostic capacity of the parameters alone and in combination. RESULTS: All the markers had prognostic capability. The levels of the three plasma activation markers correlated well with each other (median r = 0.61). They related less well with HIV RNA plasma levels (median r = 0.50) and least well with CD4 cell levels (median r = 0.36). Furthermore, plasma marker levels were shown to be able to stratify patients for prognosis within all the major categories of CD4 T-cell and HIV RNA levels. CONCLUSIONS: Plasma levels of soluble TNF-RII and other soluble markers of immune activation have prognostic capabilities which are different from HIV and CD4 T-cell levels. Combination of a single plasma activation marker measurement (such as soluble TNF-RII) with CD4 T-cell levels improved the prognostic capability of each. A new graphic technique for presenting prognostic capability indicated that plasma soluble TNF-RII and CD4 cell levels are better prognostic factors than HIV plasma level with CD4 cells < 200 x 10(6)/l. Inexpensive tests for one of the plasma activation markers, such as soluble TNF-RII or neopterin, can be useful for evaluations of HIV disease course, especially when expensive equipment, technical expertise and funding required for flow cytometry and for HIV load measurements are not readily available.     

Perinatal transmission of HIV in women receiving zidovudine: abstract and commentary

We describe a case of thrombotic thrombocytopenic purpura (TTP) resistant to conventional therapy with fresh-frozen plasma (FFP)-plasma exchange (PEX) as well as to steroids, immunoglobulins, vincristine, dipyridamole, dextran and iloprost, achieving complete remission with cryosupernatant-plasma exchange. Our case shows the effectiveness of cryosupernatant PEX, when FFP-PEX and alternative therapies have failed.     

The effectiveness of combined saquinavir and ketoconazole treatment in reducing HIV viral load

With the advent of protease inhibitors, the treatment of persons infected with the human immunodeficiency virus (HIV) has resulted in lower levels of the virus in the blood. The first of these protease inhibitors was saquinavir, which inhibits the HIV protease enzyme responsible for post-translational processing of Gag and Gag-Po1 poly protein precursors into their functional products. Studies have suggested that ketoconazole, given in combination with saquinavir, increases the bioavailability of saquinavir. This study compared the HIV viral load in patients treated with saquinavir alone and in combination with ketoconazole. Results showed that while all patients who received saquinavir exhibited a positive response, patients who also received ketoconazole had a greater drop in viral load levels. In addition, a greater number of patients had undetectable viral levels after 3 months on the ketoconazole/saquinavir regimen. These results indicate that the combination of saquinavir/ketoconazole for the treatment of HIV requires further study.     

Gynaecological conditions associated with HIV infection in women who are partners of HIV-positive Thai blood donors

Women who were partners of HIV-positive blood donors were enrolled in a study of heterosexual HIV transmission between March 1992 and December 1996 and were interviewed and examined. Gynaecological conditions, including cervical dysplasia, human papillomavirus (HPV) infection, gonorrhoea, chlamydial infection, trichomoniasis, bacterial vaginosis, vaginal candidiasis and syphilis were assessed in addition to HIV status and CD4 level. Of 481 women enrolled, 224 (46.6%) were HIV seropositive. HIV-infected women were more likely to have abnormal vaginal discharge on physical examination (OR=2.6, P <0.01), HPV infection with a high-risk type (OR=6.9, P <0.01), and cervical dysplasia (OR=5.3, P <0.01). The prevalence of other gynaecological conditions detected at the enrolment visit did not differ by HIV status. History of prior STD (OR=2.0, P <0.01) was more common among HIV-infected women. The median CD4 count was 400 cells/microl among HIV-infected women. The prevalence of abnormal vaginal discharge and bacterial vaginosis increased significantly with decreasing CD4 count. The prevalence of ectopy, vaginal candidiasis, and cervical dysplasia increased with decreasing CD4 count, but these trends were not significant. We conclude that HIV-infected Thai women appear to have increased prevalences of abnormal vaginal discharge, squamous intraepithelial lesions and self-reported history of STD.     

Internalized heterosexism among HIV-positive, gay-identified men: Implications for HIV prevention and care.

Internalized heterosexism (IH), or the internalization of societal antihomosexual attitudes, has been consistently linked to depression and low self-esteem among gay men, and it has been inconclusively associated with substance use and sexual risk in gay and bisexual men. Using structural equation modeling, the authors tested a model framed in social action theory (C. K. Ewart, 1991, 2004) in which IH is associated with HIV transmission risk and poor adherence to HIV antiretroviral therapy (ART) through the mechanisms of negative affect and stimulant use. Data from a sample of 465 gay-identified men interviewed as part of an HIV risk reduction behavioral trial were used to test the fit of the model. Results support the hypothesized model in which IH was associated with unprotected receptive (but not insertive) anal intercourse with HIV-negative or unknown HIV status partners, and with ART nonadherence indirectly via increased negative affect and more regular stimulant use. The model accounted for 15% of the variance in unprotected receptive anal intercourse and 17% of the variance in ART nonadherence. Findings support the potential utility of addressing IH in HIV prevention and treatment with HIV-positive gay men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA

Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control of human immunodeficiency virus-type 1 (HIV-1) infection, it has not been possible to demonstrate a direct relation between CTL activity and plasma RNA viral load. Human leukocyte antigen-peptide tetrameric complexes offer a specific means to directly quantitate circulating CTLs ex vivo. With the use of the tetrameric complexes, a significant inverse correlation was observed between HIV-specific CTL frequency and plasma RNA viral load. In contrast, no significant association was detected between the clearance rate of productively infected cells and frequency of HIV-specific CTLs. These data are consistent with a significant role for HIV-specific CTLs in the control of HIV infection and suggest a considerable cytopathic effect of the virus in vivo.     

Interrelationship between the duration of HIV infection, viral load and CD4 positive lymphocyte count

BACKGROUND: The decline in CD4+ lymphocytes occurs at different rates in patients with HIV infection. A longer duration of HIV infection and a higher level of viral replication, represented by the viral load, are associated with a lower CD4+ lymphocyte count. However, the interelationship between these variables is still not well known. PATIENTS AND METHODS: 107 HIV-infected patients for whom the date of infection was known, were included in a transversal study, in which the CD4+ lymphocyte count and the plasma viral load were analysed, the last using an isothermal amplification method (NASBA). Patients were not receiving antiretroviral drugs or suffered intercurrent infections at the time of the study. RESULTS: The mean duration of HIV infection was 8.6 +/- 2.9 years. The mean CD4+ lymphocyte count was 366 +/- 264 x 10(6)/l. The mean plasma viraemia was 4.3 +/- 0.9 logs. In a linear regression model, the CD4+ lymphocyte count was explained in 21.7% of cases by the duration of HIV infection, meanwhile the viral load justified up to 36.2 of CD4+ cell variability. When both parameters were combined, up to 58.4% of CD4+ lymphocyte values were explained. In this model, changes of 1 log in viral load had a 4-fold higher effect on the CD4+ cell count than each year of HIV infection. CONCLUSIONS: The duration of HIV infection and, particularly the viral load strongly influences the current CD4+ lymphocyte count, although other variables should exist (virus with syncytium-inducing phenotype, age of the patient and his immunegenetic repertoire) influencing the different decline seen in CD4+ T-cells.     

HIV infection in women and children. Special concerns in prevention and care

Unfortunately, HIV infection continues to spread rapidly among women in the United States, and infected women still have a poorer outcome than do infected men. Prevention, early diagnosis, and facilitation of care in women are critical to both their own and their children's health. Fortunately, significant advances continue to be made in prevention of HIV transmission to children. Not only HIV experts but also primary care physicians play an important role in identification and care of HIV-infected women and children. In addition, prevention of HIV infection requires the efforts of professionals throughout the healthcare spectrum.     

Factors associated with vaginal yeast infections in HIV-positive women

To better understand factors associated with symptomatic and asymptomatic vulvovaginal candidiasis, including the role of immune compromise and patient self-report, a cross-sectional analysis of factors associated with the isolation of yeast from vaginal swabs and clinical diagnosis of Candida vaginitis (CV) among 184 HIV-infected women was conducted. Sixty-four (35%) of the women had vaginal swabs positive for yeast. Nineteen (10%) women met the case definition for CV. In a logistic regression model, only CD4 < or = 100 cells/mm3 was predictive of CV (adds ratio = 4.5; 95% confidence interval = 1.0, 20; p = .05). The predictive value of patient self-report of CV was only 12%. This study demonstrates that all HIV-infected women should receive a regular and thorough gynecologic evaluation, regardless of self-reported symptoms. HIV-infected women will benefit from education about prevention and treatment of CV, and women whose CD4 counts are low may wish to consider prophylaxis for CV.     

Conscientiousness predicts disease progression (CD4 number and viral load) in people living with HIV.

Objective: Psychosocial factors (e.g., depression, avoidant coping, life stress) have been related to disease progression in HIV. This study examined the relationship between the Big Five Conscientiousness factor and HIV disease progression (CD4 cell and viral load) over 1 year in 119 seropositive participants. The study also examined whether Conscientiousness effects were mediated by adherence, perceived stress, depression, or coping measures. Design: In a 1-year longitudinal design, participants completed the NEO Five-Factor Inventory Conscientiousness scale (P. T. Costa & R. R. McCrae, 1992). Participants also completed psychosocial assessments and underwent blood draws at initial assessments and 1-year follow-up. Main Outcome Measures: Multiple hierarchical regression models were used to predict change in CD4 cell numbers and viral load log 10, controlling for demographic variables, initial disease status, and antiretroviral medications. Results: Conscientiousness predicted significant increases in CD4 number and significant decreases in viral load at 1 year. Conscientiousness was related positively to medication adherence and active coping and negatively to depression and perceived stress. Only perceived stress emerged as a possible mediator. Conclusion: The significant relationship between Conscientiousness and medication adherence, distress, and coping suggests that an assessment of Conscientiousness in patients with HIV may help specify or target behavioral interventions to promote optimal disease management. (PsycINFO Database Record (c) 2010 APA, all rights reserved)