The most award winning
healthcare information source.
TRUSTED FOR FOUR DECADES.
Editor’s Note: In this feature, brief items, primarily gleaned from abstracts or articles in journals and other resources not commonly perused by most US infectious disease physicians, will be presented, usually without comment. — Stan Deresinki, MD, FACP
|HIV Infection & Complications (Cont. from Nov. 1, 2002 issue)|
Chloroquine Inhibits HIV
Chloroquine, at clinically relevant concentrations, inhibits HIV-1 and HIV-2 in vitro at a postintegration step affecting the structural integrity of newly produced viral envelope glycoproteins (Savarino A, et al. AIDS. 2002;15:2221-2229).
Simplification’ of Antiretroviral Therapy
HIV-infected patients receiving a PI plus nucleoside analogs and who had suppressed viral replication as well as absence of the RT 215 mutation were randomized to continue their regimen or to change to treatment with abacavir/lamivudine/zidovudine. Virologic failure after a median of 84 weeks occurred in 6% of the continuation and 15% of the switch group (P = 0.081); prior zidovudine monotherapy and "archived" RT mutations were significantly associated with failure (Opravil M, et al. J Infect Dis. 2002;185:1251-1260).
CD4+ NK Cells and Persistent HIV Infection
A subset of NK cells expressing CD4 serves as a persistent reservoir of HIV-1 in patients receiving HAART (Valentin A, et al. Proc Natl Acad Sci USA. 2002;99:7015-7020; Kolte L, et al. J Infect Dis. 2002;185:1578-1585).
Cyclophosphamide and HAART
The addition of cyclophosphamide to antiretroviral therapy failed to diminish the cellular reservoir of HIV (Bartlett JA, et al. AIDS Res Hum Retroviruses. 2002;18:535-543).
Intermittent HAART is Predictive of Mortality
Multivariate analysis of a large cohort of patients who started HAART between 1996 and 1999 found that those who took their drugs intermittently were approximately 3 times more likely to die after 1 year of follow-up than those who took them continuously (Hogg RS, et al. AIDS. 2002;16:1051-1058).
Why Does the CD4+/CD8+ Ratio Fail to Normalize in Some Successful HAART Recipients?
A statistically significant inverse correlation was found between the frequency of CD4+ T cells carrying HIV-1 proviral DNA and the CD4+/CD8+ T-cell ratio in individuals with prolonged suppression of plasma HIV RNA during HAART therapy. It is suggested that this evidence of low-level viral replication, while insufficient for the maintenance of HIV-1-specific CTL responses, accounts for the lack of normalization of the CD4+/C8+ ratios in some patients with virological suppression during HAART (Chun TW, et al. J Infect Dis. 2002;185:1672-1676).
Apoptosis, Response to IL-2, & Discordant Responses
Failure of CD4 count to rapidly rise despite virological suppression was associated with underexpression of the anti-apoptic molecule Bcl-2 and increased susceptibility to spontaneous apoptosis, together with decreased responsiveness to IL-2 (David D, et al. AIDS. 2002; 16:1093-1101).
Drug Resistance Mutations & Discordant Responses
RT mutations, M184V and protease mutations, L24I and V82A were significantly associated with increased CD4 count despite virological failure, while RT Y181C was associated with a reduced probability of immunologic recovery (Antinori A, et al. AIDS. 2001;15:2325-2327).
Low-Level Viremia & Virological Treatment Failure
Evaluation of virus from 14 patients on ART who developed persistent low-level viremia (reaching a median of 1450 copies/mL) after an initial decrease to < 500 copies/mL detected the presence of new primary resistance mutations in 93%. Aleman and colleagues conclude that low-level viremia after virological treatment failure can select for virus with several new drug resistance mutations and that this serial accumulation of mutations will limit future treatment options (Aleman S, et al. AIDS. 2002;16:1039-1044).
Amprenavir and Lopinavir Cross-Resistance
In vitro exposure to increasing concentrations of amprenavir was associated with progressive accumulations of mutations at protease codons 10, 46, 47, 50, and 84, as well as at Gag codon 449 and at the p1/p6 cleavage site. Phenotypic susceptibility to amprenavir was progressively reduced with increasing numbers of protease mutations and changes in susceptibility to lopinavir-paralleled changes in amprenavir susceptibility. The presence of either 184V or 150V mutations was associated with a reduction in replicative capacity of at least 90% (Prado JG, et al. AIDS. 2002;16:1009-1017).
Mitochondrial Function During HAART
Evaluation of 8 HIV-infected patients with lipodystrophy or elevated p-lactate while receiving HAART showed, relative to controls, reduced work capacity and a trend toward reduced maximal oxygen consumption, but a normal increase in blood lactate during exercise and no evidence of serious damage to skeletal muscle mitochondrial function (Roge BT, et al. AIDS. 2002;16:973-982).
Statins & Polyneuropathy
A case control study found a significantly increased risk of idiopathic polyneuropathy (odds ratio, 4.6) in patients who had received statins for 2 or more years (Gaist D, et al. Neurology. 2002;58:1333-1337).
Leukoencephalopathy in HAART Recipients
Postmortem examination of the brains of 7 HAART-experienced but severely immunocompromised patients (6 with poor control of HIV replication) with leukoencephalopathy found evidence of intense perivascular infiltration by HIV-gp41 immunoreactive mononuclear cells, together with myelin loss, axonal injury, and glosis. Langford and associates suggest that the pathology may be the result of HAART-associated immune reconstitution (Langford TD, et al. AIDS. 2002;16:1019-1029).
CMV in CSF in AIDS
Cell-associated CMV DNA was detected in the CSF of 8 of 9 AIDS patients independently of the presence of neurological symptoms (Stanojevic M, et al. Virus Research. 2002;85:117-122).
Aseptic Meningitis, Optic Neuritis, & Aseptic Meningitis due to VZV in an AIDS Patient
An HIV-infected patient presented with VZV meningitis and retrobulbar optic neuritis that preceded the onset of progressive outer retinal necrosis (FrancoParedes C, et al. AIDS. 2002;16:1045-1049).
Recurrent Pneumococcal Disease in HIV-Infected Patients
The recurrence rate of invasive pneumococcal disease was 6.4-fold higher in HIV-infected individuals than in those not HIV-infected and was due to reinfection rather than relapse in most (McEllistrem MC, et al. J Infect Dis. 2002;185;1364-1368).
HIV and Syphilis—Treatment Failure
Of 18 HIV-infected patients in Mozambique with latent syphilis treated with 2 M IU IM q.d. of the combination of benzylpenicillin G and the repository form benzylpenicillin G evaluated 1 year later, 9 (44.4%) had serological failure as defined by the continued presence of a positive RPR (Tattevin P, et al. Scand J Infect Dis. 2002;34:257-261).
HIV-1, HIV-2, and Tuberculosis Incidence and Mortality
A study in Guinea-Bissau found that, compared to non-HIV infected individuals, HIV-2 infection was associated with an increased incidence of tuberculosis, while HIV-1 infection (with or without concomitant HIV-2 infection) was associated with both an increase in tuberculosis incidence and associated mortality (Seng R, et al. AIDS. 2002;16:1059-1066).
Cryptococcal Disease in Uganda
Prospective evaluation of a large cohort of HIV-infected adults in Entebbe, Uganda, found that cryptococcal disease occurred at a rate of 40.4 per 1000 person-years and was associated with 17% of all the deaths in the cohort. The median survival after diagnosis was only 26 days (range, 0-128 days) (French N, et al. AIDS. 2002;16:1031-1038).
Immunopathogenesis of Lethal PCP
Studies in a murine model of PCP found that adoptive transfer of CD25-CD4+ T cells was associated with a reduced organism load but led to lethal pneumonia while transfer of the putatively regulatory CD25+CD4+ T cells suppressed this immune response and prevented the development of lethal pneumonia. This is consistent with the notion that PCP in immunocompromised patients results from a deficiency in regulatory T cells in a PC colonized individual (Hori S, et al. European J Immunol. 2002;32:1282-1291).
Ritonavir & KS
Ritonavir was shown to have direct in vitro antiangiogenic and antitumorigenic effects against Kaposi sarcoma (Pati S, et al. Blood. 2002;99:3771-3779).
Phase I Trial of IL-12
IL-12 administration was well tolerated in a Phase I placebo-controlled trial, but did not improve antigen-specific immune responses and did not affect HIV viral load (Jacobson MS, et al. AIDS. 2002;16:1147-1154).
Chlamydia pneumoniae & Temporal Arteritis—Not!
No evidence of C pneumoniae DNA was found by PCR in temporal artery biopsies of 90 patients with temporal arteritis (Regan MJ, et al. Arthritis Rheum. 2002;46:1056-1060).
Maternal Antibody to TSST-1 May Protect Infants Against Kawasaki Syndrome
Studies of maternal-infant pairs found evidence that Kawasaki syndrome in infants younger than 6 months of age is related to exposure to TSST-1 and that maternal antibody against this superantigen may be protective (J Infect Dis. 2002;185:1677-1680).
Early IVIG in Kawasaki Syndrome
Administration of IVIG to children with Kawasaki syndrome within 5 days of the onset of fever was associated with a reduced frequency of coronary ectasia at 12 months when compared with administration during days 6 to 9 after fever onset (Tse SML, et al. J Pediatr. 2002; 14:450-455).
Cats in Norway Do Not Have Bartonella Bacteremia
None of 100 cats examined in Norway were bacteremic with B henselae and only 1 was antibody positive. Human cat scratch disease is rare in Norway (Bergh K, et al. APMIS. 2002;110:309-314).
Tula Virus Infection
A 12-year-old Swiss boy developed a paronychium, fever and rash after being bitten by a wild rodent in the first reported human case of infection by Tula virus, a known hantavirus previously believed to be nonpathogenic in humans (Schultze A, et al. Eur J Clin Microbiol Infect Dis. 2002;21:304-306).
Readers are Invited
Readers are invited to submit questions or comments on material seen in or relevant to Infectious Disease Alert. Send your questions to: Rob Kimball—Reader Questions, Infectious Disease Alert, c/o American Health Consultants, P.O. Box 740059, Atlanta, GA 30374, or via the Internet by sending e-mail to email@example.com. We look forward to hearing from you.
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.