Table of Contents

• Effects of Multiple Virus Coinfections on Disease Progression in HIV-Positive Patients
• Results of a Physician Survey on Ordering Viral Load Testing
• Effect of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Survival in HIV-Associated Advanced Kaposi's Sarcoma Patients Treated With Chemotherapy
• Immune Deficiency and Risk for Malignancy Among Persons With AIDS

Effects of Multiple Virus Coinfections on Disease Progression in HIV-Positive Patients

B. Shieh et al.

Objective: Since virus infections in AIDS patients are mostly inevitable and as they frequently cause disease deterioration and therapeutic failures, a comprehensive investigation was made of the influence of the coinfections of nine well-known viruses on disease progression in patients infected with human immunodeficiency virus type 1 (HIV).

Methods: A cross-sectional study of 62 HIV-positive patients was conducted to correlate the prevalence rates for the nine viruses with the alanine aminotransferase (ALT) levels and CD4 cell counts of the patients.

Results: The rates of HIV-positive patients infected with the nine viruses are significantly higher than those of the control groups. Furthermore, almost one third of the patients in the studied group was coinfected with transfusion-transmitted virus (TTV) and manifested significantly higher ALT levels (p=0.020), and these were raised further if coinfection with TTV and human hepatitis C virus had occurred (p=0.010). By analyzing CD4 cell counts, the only significant effect on AIDS progression which could be detected was coinfection with human herpesvirus 8.

Conclusion: This result confirmed that immune-suppressed persons are more vulnerable to common virus infections. Unlike hepatitis B or C virus, TTV seems to accelerate the progression of chronic hepatitis in HIV-infected patients.

[Intervirology 2003;46(2):105-13.]

Results of a Physician Survey on Ordering Viral Load Testing

L.K. Hofherr et al.

Objective: To profile physicians' practices, utilization, and understanding of human immunodeficiency virus type 1 RNA (viral load) testing and the laboratory's role in this testing.

Design: Cross sectional study using a 34-item self-report survey mailed to physicians identified as requesting viral load testing, with follow-up mailings to nonresponders.

Participants: A sampling of U.S. physicians specializing in infectious diseases, internal medicine, and family practice associated with high, medium, and low human immunodeficiency virus/acquired immunodeficiency syndrome incidence areas.

Results: Most respondents using viral load results were infectious diseases specialists practicing in urban areas. The reasons most frequently given for requesting viral load testing were 1) to assist in patient follow-up or monitoring (75.4 percent), and 2) to initiate/guide therapy (62.5 percent). Respondents indicated that the interpretation and use of viral load results presented difficulty in the areas of patient treatment and in determining what change from baseline was clinically significant. Few respondents used the testing laboratory pathologist as a resource for interpreting viral load test results.

Conclusion: Our study indicates that physicians have questions about 1) the meaning of viral load tests, 2) how often to monitor the viral load, and 3) what change from baseline of the viral load is significant. Few physicians avail themselves of the expertise available in the laboratory for testing viral loads and interpreting such results.

[Arch Pathol Lab Med 2003;127(4):446-50.]

Effect of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Survival in HIV-Associated Advanced Kaposi's Sarcoma Patients Treated With Chemotherapy

H. Leitch, M. Trudeau and J.P. Routy

Objective: To determine whether the use of protease inhibitor (PI)-based antiretroviral (ARV) therapy had an impact on the survival of patients with human immunodeficiency virus (HIV) infection-associated Kaposi's sarcoma (KS) who were receiving systemic chemotherapy.

Method: Records of 48 AIDS patients with extensive KS who received chemotherapy from 1995 to 1999 were reviewed. Analysis by presence or absence of PI treatment was undertaken, and patients who were receiving nonnucleoside reverse transcriptase inhibitors (NNRTIs) were excluded from the analysis.

Results: Median age was 38 years, and 47 patients were men having sex with men. Half of the patients (54 percent) had at least one prior AIDS-defining event. Median CD4 count at diagnosis of KS was 28 cells/µL (range, 1-625). Visceral KS was present in 33 patients (69 percent), and the remainder of patients had extensive and symptomatic cutaneous and/or mucous membrane involvement. All patients received at least one cycle of chemotherapy, including vincristine/bleomycin or an anthracycline-containing regimen. There was a significant difference in the median survival (MS) between the 28 patients (58 percent) treated with PI-based antiretroviral therapy (31 months [range, 1.8-48]) and the group not receiving PI (seven months [range, 1-28], p=.0001). In addition, 81 percent of patients in the PI group were alive at 18 months from initiation of chemotherapy versus 12 percent in the non-PI group. Twenty patients (71 percent) in the PI-treated group were able to discontinue chemotherapy for at least one month after remission of KS, in comparison to 3 of 20 (15 percent) patients in the group of patients who did not receive PI (p=.00001). Death due to KS occurred in six of 28 (21 percent) patients (total nine deaths) in the PI group and 14 of 20 (70 percent) patients (total 18 deaths) in the non-PI group (p=.001).

Conclusion: In a nonselected group of patients with advanced and extensive KS in a real-life clinical setting, our results show a survival benefit and a decrease in KS-related death for patients receiving chemotherapy and PI-based ARV therapy when compared to patients not receiving PI-based therapy. Discontinuation of chemotherapy in patients receiving PI-based antiretroviral therapy appears to be feasible in patients who attain remission of KS.

[HIV Clin Trials 2003;4(2):107-114.]

Immune Deficiency and Risk for Malignancy Among Persons With AIDS

S.M. Mbulaiteye, R.J. Biggar, J.J. Goedert and E.A. Engels

Background: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset.

Methods: We linked records from AIDS and cancer registries in 11 U.S. regions (1990-1996). We studied 82,217 (86.6 percent) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the two years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm³ , 50-99 cells/mm³ , 100-199 cells/mm³ , and >200 cells/mm³ ) was modeled using Poisson regression.

Results: The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm³ , RRs were 1.36 (95 percent CI: 1.29-1.43) for KS and 1.48 (95 percent CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR =1.64, 95 percent CI: 1.37-1.96, per decline of 100 CD4 cells/mm³ ) and central nervous system lymphoma (RR=2.29, 95 percent CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p=.74). For non-AIDS-defining cancers (overall SIR=2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts.

Conclusion: KS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.

[J Acquir Immune Defic Syndr 2003;32(5):527-33.]