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The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)‐infected, indinavir-experienced patients, was designed to study the durability of “salvage” treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12‐16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels 500 copies/ mL at week 48. For these 86 subjects who completed 48 weeks, the median change in CD4 cell count from baseline was +72 cells/mm 3 . Greater body weight, higher CD4 cell count, and greater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly associated with durable virologic suppression. These results show that some patients who experience treatment failure can demonstrate durable virologic and immunologic responses with salvage antiretroviral regimens. Current treatment guidelines recommend starting therapy for human immunodeficiency virus (HIV) infection with 2 nucleoside analogue reverse-transcriptase inhibitors in combination with 1 or 2 protease inhibitors or a nonnucleoside analogue reversetranscriptase inhibitor [1, 2]. However, 20%‐63% of patients from clinical cohorts experience virologic treatment failure while receiving combination antiretroviral therapy [3‐7]. Recent prospective studies have attempted to identify strategies for treatment of the treatment-experienced patient [8‐13], but these studies have focused primarily on 8‐24-week virologic responses to treatment. The durability of virologic and immunologic re

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration,or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

In a case-control study to identify risk factors for fluconazole-resistant oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25 patients with clinical and in vitro fluconazole-resistant candidiasis were paired with controls who had treatment-responsive candidiasis and who had been observed for similar time periods. After their first episode of candidiasis, patients who later developed fluconazole resistance had more treated episodes than did matched controls (cases, 3.1 ; controls, 1.8 ; P =.004), lower median CD4 cell counts (11/mm 3 vs. 71/mm 3 ; P =.004), and greater median durations of all antifungal therapy (419 vs. 118 days ; P

Treatment of HIV infection in the current era is based on an understanding of this disease as a chronic viral illness characterized by progressive immunosuppression. A decline in helper T lymphocytes leaves the patient susceptible to an increasing number of infectious and neoplastic conditions. Medical therapy for patients with HIV infection centers on prevention of opportunistic infections, treatment of infectious and other consequences of immunosuppression when they do occur, and antiretroviral medications to suppress HIV replication. Recommendations for preventive therapy are based on the association of specific opportunistic infections with typical levels of immunodeficiency. Decisions on the use of antiretroviral therapy are also based on an assessment of the patient's level of immune suppression, and may additionally incorporate a measure of plasma HIV viral burden.

A rapid (time to completion, Pneumocystis carinii PCR assay with an associated internal control was developed, using fluorescence resonance energy transfer (FRET) probes for detection. The touch-down procedure significantly increased the sensitivity of the assay compared to a non-touch-down procedure. Tenfold serial dilutions of a cloned target were used as standards for quantification. P. carinii DNA has been detected in respiratory specimens from patients with P. carinii pneumonia (PCP) and from patients without clinical evidence of PCP. The latter probably represents colonization or subclinical infection. It is logical to hypothesize that quantification might prove helpful in distinguishing between infected and colonized patients: the latter group would have lower copy numbers than PCP patients. A blinded retrospective study of 98 respiratory samples (49 lower respiratory tract specimens and 49 oral washes), from 51 patients with 24 episodes of PCP and 34 episodes of other respiratory disease, was conducted. PCR-positive samples from colonized patients contained a lower concentration of P. carinii DNA than samples from PCP patients: lower respiratory tract samples from PCP and non-PCP patients contained a median of 938 (range, 2.4 to 1,040,000) and 2.6 (range, 0.3 to 248) ( P < 0.0004) copies per tube, respectively. Oral washes from PCP and non-PCP patients contained a median of 49 (range, 2.1 to 2,595) and 6.5 (range, 2.2 to 10) ( P < 0.03) copies per tube, respectively. These data suggest that this QTD PCR assay can be used to determine if P. carinii is present in respiratory samples and to distinguish between colonization and infection.