HIV Viral Dynamics of Lopinavir/Ritonavir Monotherapy as Second-Line Treatment: A Prospective, Single-Arm Trial.

BACKGROUND: Characterizing viral response to lopinavir/ritonavir (LPV/r) monotherapy as second-line treatment may guide recommendations for resource-limited settings (RLS). METHODS: We conducted a 48-week prospective, single-arm study of LPV/r monotherapy in patients failing first-line therapy in Nigeria. The primary outcome was sustained HIV-1 viral load (VL) <400 copies/mL at 48 weeks. RESULTS: Of 30 enrolled patients, 28 (93%) achieved viral suppression on LPV/r, while 29 (96%) experienced low-level viremia. At 48 weeks, 9 (30%) met the primary outcome of sustained viral suppression; 14 (47%) patients were suppressed on LPV/r in a snapshot analysis. Detectable VLs at 12 and 24 weeks were strongly associated with treatment failure at 48 weeks. New resistance mutations were not detected. The trial was stopped early due to treatment failure. CONCLUSION: In this study, the rate of virologic failure among patients on a second-line lopinavir monotherapy regimen was relatively high and predicted by early detectable viremia. However, no LPV/r-associated resistance mutations were detected despite fluctuating low-level viremia, demonstrating the high genetic barrier to resistance of the protease inhibitor class which could be useful in RLS.

Reactivation of coccidioidomycosis despite antifungal prophylaxis in solid organ transplant recipients.

BACKGROUND: Coccidioidomycosis is an airborne infection caused by the fungus Coccidioides, which is endemic to the southwestern United States. Cell-mediated immunity is required for the control of this infection, and some patients such as organ transplant recipients, who lack such immunity, have a high risk of severe, disseminated, or relapsed infection with high mortality. Previously latent coccidioidal infection can reactivate after transplantation. Antifungal prophylaxis has substantially decreased the risk of reactivated coccidioidomycosis after transplantation in these patients. METHODS: We conducted a retrospective review of all patients with coccidioidomycosis who underwent solid organ transplantation at our center to identify factors for recrudescent coccidioidomycosis (despite antifungal prophylaxis) after transplantation. RESULTS: Between June 1999 and June 2009, 100 patients with previous coccidioidomycosis underwent solid organ transplantation at our institution. Ninety-four (94%) received anticoccidioidal prophylaxis after transplantation. The six patients who did not receive such prophylaxis did not experience reactivated coccidioidomycosis. Five patients who received anticoccidioidal prophylaxis experienced reactivated infection. All five patients survived with further antifungal treatment. Among patients who experienced recrudescent infection despite antifungal prophylaxis, African American race was an identified risk factor. Pretransplant dissemination may be a risk factor for reactivated coccidioidomycosis, but this finding was not statistically significant. Whether nonadherence to prophylaxis played a small or large role is uncertain. CONCLUSIONS: Antifungal prophylaxis effectively suppressed recrudescent coccidioidomycosis after solid organ transplantation for the large majority of patients with a history of coccidioidomycosis before transplantation. Strict lifelong adherence to antifungal prophylaxis is imperative.

Coccidioides fungemia in six patients, with a review of the literature.

To identify demographics, clinical manifestations, and outcomes of patients with Coccidioides fungemia, we searched our institutional medical records to identify patients with Coccidioides fungemia treated between 1998 and 2008 and conducted a comprehensive search of the medical literature to identify previously reported cases. Coccidioides fungemia is an uncommon manifestation of coccidioidomycosis, a fungal infection caused by Coccidioides sp. endemic to the southwestern United States. Six Coccidioides fungemia patients were treated at our institution during the 10-year period. All 6 had underlying comorbid disease; three were receiving immunosuppressants. Three patients survived longer than 2 years. The literature review identified 107 patients, bringing the total cohort to 113 (mean age, 42 years). Forty-three patients (38%) had infection with the human immunodeficiency virus, 20 (18%) were receiving corticosteroids, 11 (10%) had solid organ transplants, and 5 (4%) were pregnant. Sites of extrapulmonary dissemination were reported for 97 (86%); the most common sites were liver (26/97 [27%]), spleen (21/97 [22%]), and meninges/central nervous system (17/97 [18%]). No patient showed evidence of endocarditis. At least 1 serologic test was positive in 45 (87%) of 52 patients for whom results were available. Overall mortality at 30 days was 62% (70/113; mean survival, 11.4 days). Survival was significantly worse in immunocompromised versus immunocompetent patients (22/72 [31%] vs. 19/36 [53%], respectively; P = .04). Lack of antifungal therapy predicted poor survival (8/38 [21%] vs. 32/65 [49%], respectively; P = .004). Coccidioides fungemia is an uncommon manifestation of fulminant, disseminated coccidioidomycosis. Survival is poorest in immunocompromised patients or those not receiving antifungal therapy.