Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease.

In a human immunodeficiency virus-infected subject, cytomegalovirus (CMV) isolated 9 months after the patient began oral ganciclovir prophylaxis was resistant to ganciclovir and cidofovir and contained mutations in both UL97 and Pol coding regions. At 1 year, retinitis developed, which progressed despite intravenous ganciclovir followed by foscarnet and then cidofovir. A subsequent buffy coat virus isolate was resistant to all three drugs and contained new mutations in UL97 and Pol. By individually transferring the observed mutations to laboratory strain AD169, it was shown that a mutation at codon 603 of UL97 conferred resistance to ganciclovir, a mutation at codon 412 of Pol conferred resistance to both ganciclovir and cidofovir, and a mutation at codon 802 of Pol conferred resistance to ganciclovir and foscarnet. This case illustrates the development of multidrug resistance during prolonged exposure to antiviral therapy for CMV and cross-resistance arising from point mutations in the CMV Pol gene.

HIV viral load markers in clinical practice.

Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?

Successful treatment of varicella zoster virus meningoencephalitis in patients with AIDS: report of four cases and review.

OBJECTIVE: Neurologic complications are common in patients with AIDS. Herpes zoster is a common early manifestation of HIV infection, but there have been few reports of encephalitic complications and nearly all have been postmortem. We report four cases of varicella zoster virus (VZV) meningoencephalitis diagnosed and treated antemortem, and briefly review the relevant literature. SETTING: Mount Zion Medical Center, San Francisco, California, USA. PATIENTS: Four HIV-positive male patients with antibodies to VZV in their cerebrospinal fluid. INTERVENTION: Treatment with intravenous acyclovir (three cases) and intravenous ganciclovir (one case), which resulted in resolution of all symptoms except blindness in one patient. CONCLUSION: Antibodies to VZV in the cerebrospinal fluid of HIV-positive individuals may allow early diagnosis and lifesaving treatment of VZV meningoencephalitis.

Severe opportunistic infections in AIDS patients with late-stage disease.

BACKGROUND: Clinicians caring for patients who have acquired immunodeficiency syndrome (AIDS) need to be aware of the wide variety of infectious diseases that can occur. Although Pneumocystis carinii pneumonia (PCP) is the most common AIDS-defining infection, other opportunistic infections associated with advanced immunodeficiency can develop after an initial diagnosis. METHODS: To ascertain AIDS-defining opportunistic infections that developed at the time of or after an AIDS diagnosis, and intensive chart review was conducted for 45 homosexual men with AIDS who died from 1990 through 1992. Time to death after first occurrence of these infections was also determined. RESULTS: The most common opportunistic infection occurring as the initial AIDS-defining illness was PCP (31 percent). The most common opportunistic infection occurring as a secondary disease was cytomegalovirus (CMV) disease (40 percent), followed by disseminated Mycobacterium avium complex (33 percent) and invasive candidiasis (31 percent). Each of these latter infections was associated with a poor prognosis (median time to death < or = 8 months). CONCLUSIONS: Diseases caused by CMV, disseminated M. avium complex, and invasive candidiasis were uncommon presenting manifestations of AIDS but were common secondary diseases that tended to be associated with limited survival. With increasing survival and a declining incidence of PCP as a result of medical therapy, other severe opportunistic infections might become increasingly recognized.

5-HIAA in cerebrospinal fluid and deficit schizophrenic characteristics.

Higher CSF 5-HIAA concentrations and lower CSF HVA concentrations have been associated with various measures of slowed motor behaviour and communication in schizophrenic patients. To derive a single, reliable measure of deficit characteristics in schizophrenic patients, we entered four items of the BPRS reflecting negative symptoms, a work history measure derived from the Strauss-Carpenter scale, and three subscale scores of the WAIS-R into a principal-components analysis to derive a single factor score. The CSF 5-HIAA concentrations were within the normal range of values, and correlated directly with this factor score, but CSF HVA concentrations were not associated with the deficit factor score. These findings add support to the hypothesis that brain serotonin function is associated with deficit schizophrenic characteristics.