Alison E. Heald

Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET)

To determine if positron emission tomography (PET) imaging using F-18 fluorodeoxyglucose (FDG) can accurately distinguish between malignant and infectious central nervous system (CNS) mass lesions in patients with human immunodeficiency virus (HIV) infection, a prospective case series of 18 patients with HIV infection and focal CNS lesions on computed tomography (CT) or magnetic resonance (MR) scans was analysed. The patients were divided into 3 groups based on biopsy results, serology and response to therapy. Group 1 consisted of 8 patients with infectious lesions (4 with toxoplasmosis, 2 with neurosyphilis, 2 with progressive multifocal leukoencephalopathy (PML) ). Group 2 consisted of 5 patients with biopsy proven CNS lymphoma. Group 3 consisted of 5 patients with presumed CNS lymphoma. Patients underwent FDG-PET studies as an adjunctive diagnostic procedure. The metabolic activity of each patients lesion was graded using both a qualitative visual score and a semi-quantitative count ratio comparing the lesion with contralateral brain. CNS lesions diagnosed as lymphomas had statistically higher visual scores ( P =0.001) and count ratios ( P =0.002) than CNS lesions diagnosed as infections. FDG-PET could accurately differentiate lymphoma from infections in 16 of 18 cases. Two cases of PML had high metabolic activity and could not be differentiated from lymphoma. FDG-PET shows great promise in differentiating lymphoma from infectious lesions in the CNS of patients with HIV infection. If larger prospective studies confirm this impression, more specific and rapid treatment of CNS lesions could be performed and perhaps obviate the need for brain biopsy in many cases.

Protease inhibitors are associated with a slowed progression of HIV-related renal diseases.

AIMSnWhile angiotensin-con-verting enzyme inhibitors and zidovudine may improve the course of the most common HIV-related renal disease, HIV-associated nephropathy (HIVAN), the effect of anti-retroviral combination therapy on this and other HIV-related renal diseases has not been assessed. This study describes the clinical course of HIV-related renal diseases and the effect of protease inhibitors on their progression.nnnMETHODSnThis retrospective cohort study reviews the clinical course of 19 patients with a clinical or biopsy-proven diagnosis of HIVAN or other HIV-related renal diseases. Groups progressing and not progressing to ESRD were compared using longitudinal analyses to assess the association between creatinine clearance and clinical and therapeutic factors.nnnRESULTSnThe cohort consisted of 16 African-Americans, 2 Caucasians and 1 Native American. Their modes of HIV infection were intravenous drug use (7), a history of men having sex with men (3) and heterosexual behavior (5). Patients were followed for a median of 16.6 months. Seven patients reached ESRD. Loss of creatinine clearance over time did not differ among genders, races, or patients with different modes of HIV infection. Longitudinal analyses demonstrated an association between protease inhibitors and prednisone and a slower decline in creatinine clearance in multivariable models (p = 0.04 and 0.003, respectively).nnnCONCLUSIONSnThe epidemiology and clinical course of HIV-related renal diseases is more heterogeneous than previously described. This study suggests a benefit to the use of protease inhibitors and prednisone on the progression of these nephropathies.

Association of Plasma Levels of Human Immunodeficiency Virus Type 1 RNA and Oropharyngeal Candida Colonization

The pathophysiology of oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV) type 1 is poorly understood. Association between oropharyngeal yeast carriage and various clinical factors in HIV-1-infected patients was studied in 83 patients with no clinical evidence of thrush and no recent antifungal use. Of the clinical factors measured, the only correlate of yeast colonization was with plasma HIV-1 RNA levels (P=.001), whereas the correlation with CD4 cell count was poor (P=.36). By multivariable regression modeling, plasma HIV-1 RNA was the only parameter that correlated with the extent of colonization with Candida infection (P=.003). These data indicate that the presence and amount of asymptomatic oropharyngeal yeast carriage in persons with HIV-1 infection is more significantly correlated with plasma HIV-1 RNA levels than with CD4 cell count. Further studies on the effect of HIV-1 on oropharyngeal yeast colonization, infection, and local immunity are warranted.

HIV Infection: Treatment Outcomes in Older and Younger Adults

To determine the effect of antiretroviral therapy (ART) on the immunological and virological outcomes of older human immunodeficiency virus (HIV)‐infected patients compared with younger HIV‐infected patients.

OROPHARYNGEAL YEAST FLORA AND FLUCONAZOLE RESISTANCE IN HIV – INFECTED PATIENTS RECEIVING LONG – TERM CONTINUOUS VERSUS INTERMITTENT FLUCONAZOLE THERAPY

ObjectiveTo examince the impact ot continuous versus intermittent Fluconazole therapy on fungal colonization and fluconazole resistance in the oophaynx of HIV-infected patients. DesignCase-conrol study. SetingDuke University Adult Infectious Diseases clinic, A teriary referral center in North Carolina which provies care for 700 HIV-infected persons PatientsNineteen HIV-infected patients on daily continusous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermitent luconazole for a minimum of 6 months were matched by sex and CD4 Cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months. Main oucome measuresFungal isolation an fluconazole susceptibility testing were performed on oral saline rinses from each patient ResultsThe patients taking coninuous fluconazole were more likely than matched conrols to have had sterile mouth rinses (14 out of 19 versus five out of 19; P <0.001), and the yeasts that were isolated were more likely than matched conrols o be non-cCandida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole ≤16g/ml. None of these isolates were associated with sympoms. In conrast, none of the patients in the intermitent fluconazole group had sterile cultures. When this roup was compared o conrols, they were more likely to have had non-C. Albicans species, and C. Albicans isolates obtained had higher MIC o fluconazole. ConclusionsLong-term continuous therapy wih fluconazole may prevent the appearance of Candida in the oral civity. This finding may reduce recurrence rates and miht favorably impact on the clinical appearance of mucosal candidiasis wih resistant C. albicans.

Effect of Protease Inhibitors on the Sense of Taste

The purpose of this study was to investigate the taste properties of protease inhibitors which are essential components of drug regimes used to treat human immunodeficiency virus (HIV) infection. In this study, the taste properties of four protease inhibitors (indinavir, ritonavir, saquinavir, and nelfinavir) were investigated in unmedicated HIV-infected patients and healthy controls. Three of the four protease inhibitors (indinavir, ritonavir, and saquinavir) were found to be predominantly bitter (with additional qualities of medicinal, metallic, astringent, sour, and burning). Nelfinavir was found to be relatively tasteless. HIV-infected and uninfected control subjects detected protease inhibitors at similar concentrations, but HIV-infected subjects perceived suprathreshold concentrations as more bitter than controls. Detection thresholds ranged from 0.0061 mM for saquinavir in HIV-infected patients to 0.0702 mM for ritonavir in uninfected control subjects. Suprathreshold studies indicated that protease inhibitors modified the taste perception of a variety of other taste compounds. These results are consistent with clinical findings that protease inhibitors produce taste complaints that can impact patient compliance.

Taste and smell losses in HIV infected patients

Human immunodeficiency virus (HIV-1) associated wasting is an increasingly common clinical manifestation of AIDS. The pathogenesis of wasting is multifactorial and includes reduced caloric intake as a major contributing mechanism. The perceptions of taste and smell play an important role in stimulating caloric intake and in optimizing nutrient absorption through cephalic phase reflexes. The purpose of this study was to evaluate the degree of losses in taste and smell function that occur in subjects infected with HIV. Taste and smell function was evaluated in 40 HIV infected individuals and 40 healthy control subjects matched for age, sex, race, smoking behavior, and number of years of education. Chemosensory tests administered to subjects included taste and smell detection thresholds, taste and smell memory tests, taste and smell discrimination tests, and taste and smell identification tasks. Significant differences were observed between experimental and control subjects in glutamic acid taste detection threshold (p < 0.001), quinine hydrochloride taste detection threshold (p < 0.001), menthol smell detection threshold (p < 0.001) and in the taste identification task (p = 0.006). Overall the results suggest abnormalities in the peripheral and central nervous systems, and subjective distortion of taste and smell. A significant correlation was not established between CDC classification of HIV infection and taste and smell function, although trends were observed suggesting worsening function with progression of HIV disease. These results document significant taste and smell losses in HIV infected subjects which may be of clinical significance in the development or progression of HIV associated wasting.

A prospective study of discontinuing primary and secondary Pneumocystis carinii pneumonia prophylaxis after CD4 cell count increase to > 200 x 106/l

Objective To assess the incidence of Pneumocystis carinii pneumonia (PCP) after discontinuation of either primary or secondary prophylaxis. Design This was a prospective, non-randomized, non-blinded study. Setting Twenty-five University-based AIDS Clinical Trials Group units. Participants Participants either had a CD4 cell count ⩽ 100 × 106/l at any time in the past and no history of confirmed PCP (group I; n = 144), or had a confirmed episode of PCP ⩾ 6 months prior to study entry (group II; n = 129). All subjects had sustained CD4 cell counts > 200 × 106/l in response to antiretroviral therapy. Interventions Subjects discontinued PCP prophylaxis within 3 months or at the time of study entry. Evaluations for symptoms of PCP and CD4 cell counts were performed every 8 weeks. Prophylaxis was resumed if two consecutive CD4 cell counts were < 200 × 106/l. Main outcome measure(s) The main outcome was development of PCP. Results No cases of PCP occurred in 144 subjects (median follow-up, 82 weeks) in group I or in the 129 subjects (median follow-up, 63 weeks) in group II (95% upper confidence limits on the rates of 1.3 per 100 person-years and 1.96 per 100 person-years for groups I and II, respectively). Eight subjects (five in group I and three in group II) resumed PCP prophylaxis after two consecutive CD4 cell counts < 200 × 106/l. Conclusions The risk of developing initial or recurrent PCP after discontinuing prophylaxis is low in HIV-infected individuals who have sustained CD4 cell count increases in response to antiretroviral therapy. Neither lifelong primary nor secondary PCP prophylaxis is necessary.

Effect of antimicrobial and anti-inflammatory medications on the sense of taste.

Elderly individuals and HIV-infected patients have a disproportionate number of taste complaints relative to the general population, and these taste alterations are correlated with the use of medications. Clinical reports of taste disorders have been associated with many drugs, including antimicrobial and anti-inflammatory medications. The purpose of this study was to quantify the taste effects of 6 nonsteroidal anti-inflammatory drugs (NSAIDS) and 13 antimicrobial drugs. The six NSAIDS were: diclofenac sodium salt, fenoprofen calcium salt, ibuprofen, ketoprofen, nabumetone, and sulindac. The 13 antimicrobials were: acyclovir, ampicillin, atovaquone, dapsone, enoxacin, ethambutol, lomefloxacin HCl, ofloxacin, pentamidine isethionate, pyrimethamine, sulfamethoxazole, tetracycline HCl, and trimethoprim. These 19 medications were applied topically to the tongues of unmedicated young and elderly volunteers as well as unmedicated HIV-infected patients to measure the direct effect of the drug on taste receptors. Topical application of drugs to the apical tongue surface was used to mimic the situation in which the drug is secreted into the saliva. The main finding was that the taste qualities of these drugs were perceived as predominantly bitter, metallic, and/or sour, although several did not have a taste. Elderly subjects had higher thresholds than young subjects for one-third of the drugs that were tested. Thresholds for HIV-infected patients were statistically equivalent to young controls; however, HIV-infected patients rated the drugs as more intense at four times above the detection threshold than young subjects. Most of these drugs when applied directly to the tongue also modified the taste intensity of other tastants (e.g., NaCl, citric acid).

Effect of the nucleoside analogs zidovudine didanosine, stavudine, and lamivudine on the sense of taste

The purpose of this study was to investigate the taste properties of nucleoside analogs, which are among the current medications used to treat human immunodeficiency virus (HIV) infection. Eighteen unmedicated HIV-positive subjects and 41 healthy control subjects participated in threshold and suprathreshold experiments. All of the nucleoside medications tested were perceived as predominantly bitter (along with other qualities such as metallic, medicinal, sour, astringent, and cooling). The nucleoside analog with the lowest detection thresholds was zidovudine; the detection threshold was 1.47 mM for HIV-infected patients and 2.15 mM for control subjects. Detection thresholds for lamivudine were 4.41 mM for HIV-infected patients and 4.36 mM for control subjects. Detection thresholds for stavudine were 6.39 mM for HIV-infected patients and 5.99 mM for control subjects. Detection thresholds for didanosine were 14.29 mM for HIV-infected patients and 24.0 mM for control subjects. The nucleoside analogs also modified the taste perception of KCl and CaCl2. There were no significant differences between HIV-infected subjects and control subjects for detection threshold values for any of the drugs. However, HIV-infected subjects rated lamivudine, zidovudine, and stavudine as significantly more bitter than did the control subjects at concentrations four times higher than their detection thresholds. This result was not due to use of medications by HIV-infected subjects because none of the subjects (neither HIV-infected nor control) were taking medications.