Biomedical subjects
Reto Nüesch
Publications and source records attributed to Reto Nüesch.
CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.
BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.
Immunological recovery and antiretroviral therapy in HIV-1 infection.
Potent antiretroviral therapy has dramatically improved the prognosis of patients infected with HIV-1. Primary and secondary prophylaxis against Pneumocystis carinii, Mycobacterium avium, cytomegalovirus, and other pathogens can be discontinued safely once CD4 cell counts have increased beyond pathogen-specific thresholds. Approximately one-third of individuals receiving antiretroviral therapy will not reach CD4 cell counts above 500 cells per muL after 5 years despite continuous suppression of plasma HIV-1 RNA. Whether this failure represents a risk factor for the long-term incidence of opportunistic diseases--eg, tuberculosis or malignancies--remains uncertain. We describe the time course of CD4 cell concentrations in patients whose plasma HIV-1 RNA is durably suppressed by antiretroviral therapy, in patients with incomplete suppression of plasma HIV-1 RNA, and during treatment interruptions. In addition, immune reconstitution disease, an inflammatory syndrome associated with immunological recovery occurring days to weeks after the start of antiretroviral therapy, is briefly described.
Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas.
BACKGROUND: Microscopic diagnosis of malaria is unreliable outside specialized centers. Rapid tests have become available in recent years, but their accuracy has not been assessed systematically. PURPOSE: To determine the accuracy of rapid diagnostic tests for ruling out malaria in nonimmune travelers returning from malaria-endemic areas. DATA SOURCES: The authors searched MEDLINE, EMBASE, CAB Health, and CINAHL (1988 to September 2004); hand-searched conference proceedings; checked reference lists; and contacted experts and manufacturers. STUDY SELECTION: Diagnostic accuracy studies in nonimmune individuals with suspected malaria were included if they compared rapid tests with expert microscopic examination or polymerase chain reaction tests. DATA EXTRACTION: Data on study and patient characteristics and results were extracted in duplicate. The main outcome was the likelihood ratio for a negative test result (negative likelihood ratio) for Plasmodium falciparum malaria. Likelihood ratios were combined by using random-effects meta-analysis, stratified by the antigen targeted (histidine-rich protein-2 [HRP-2] or parasite lactate dehydrogenase [LDH]) and by test generation. Nomograms of post-test probabilities were constructed. DATA SYNTHESIS: The authors included 21 studies and 5747 individuals. For P. falciparum, HRP-2-based tests were more accurate than parasite LDH-based tests: Negative likelihood ratios were 0.08 and 0.13, respectively (P = 0.019 for difference). Three-band HRP-2 tests had similar negative likelihood ratios but higher positive likelihood ratios compared with 2-band tests (34.7 vs. 98.5; P = 0.003). For P. vivax, negative likelihood ratios tended to be closer to 1.0 for HRP-2-based tests than for parasite LDH-based tests (0.24 vs. 0.13; P = 0.22), but analyses were based on a few heterogeneous studies. Negative likelihood ratios for the diagnosis of P. malariae or P. ovale were close to 1.0 for both types of tests. In febrile travelers returning from sub-Saharan Africa, the typical probability of P. falciparum malaria is estimated at 1.1% (95% CI, 0.6% to 1.9%) after a negative 3-band HRP-2 test result and 97% (CI, 92% to 99%) after a positive test result. LIMITATIONS: Few studies evaluated 3-band HRP-2 tests. The evidence is also limited for species other than P. falciparum because of the few available studies and their more heterogeneous results. Further studies are needed to determine whether the use of rapid diagnostic tests improves outcomes in returning travelers with suspected malaria. CONCLUSIONS: Rapid malaria tests may be a useful diagnostic adjunct to microscopy in centers without major expertise in tropical medicine. Initial decisions on treatment initiation and choice of antimalarial drugs can be based on travel history and post-test probabilities after rapid testing. Expert microscopy is still required for species identification and confirmation.
Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients.
OBJECTIVE: To evaluate the efficacy and safety of simplified maintenance therapy (SMT) compared with continued protease inhibitor (PI) therapy. DESIGN: Meta-analysis of nine randomized controlled trials in which 833 patients were switched to SMT (abacavir, efavirenz or nevirapine) and 616 continued PI, assessing virologic failure (primary outcome), discontinuation of therapy for reasons other than virologic failure, CD4 cell count, total plasma cholesterol and triglycerides. RESULTS: The risk ratio for virologic failure for SMT compared to continued PI was 1.06 [95% confidence interval (CI) 0.58-1.92; test for homogeneity P = 0.01] for SMT, 2.56, (95% CI, 1.17-5.64) for abacavir, 0.83 (95% CI, 0.36-1.91) for efavirenz and 0.54 (95% CI, 0.29-1.02) for nevirapine. The risk ratio for premature discontinuation of therapy with SMT was 0.61 (95% CI, 0.48-0.77; test for homogeneity P < 0.10). The difference in absolute mean cholesterol for SMT compared to continued PI was -0.15 mmol/l, (95% CI, -0.40 to 0.09; test for homogeneity P < 0.01) for SMT, -0.51 mmol/l (95% CI, -0.70 to -0.33) for abacavir, 0.22 mmol/l (95% CI, 0 to 0.43) for efavirenz and -0.19 mmol/l (95% CI, -0.48 to 0.09) for nevirapine. CONCLUSIONS: Current evidence suggests that SMT with abacavir rather than continued PI increases the risk of virologic failure, this increased risk may be confined to patients with prior mono or dual therapy with reverse transcriptase inhibitors. There is not enough evidence on whether SMT with efavirenz and nevirapine influences the risk of virologic failure. SMT with any of the three drugs reduces the risk of discontinuation of therapy, and SMT with abacavir reduces plasma cholesterol.