Development of a real-time PCR for Bartonella spp. detection, a current emerging microorganism.

A real-time PCR assay using SYBR Green was optimized to detect those Bartonella that are most frequently described as pathogens. The assay was genus-specific. Sequencing allowed to distinguish species. Assay sensitivity was determined using 10-fold serial dilutions of genomic DNA. Dynamic range was 100 ng-100 fg and sensitivity was 50 copies/reaction.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

Randomized Trial of Clarithromycin for Mediterranean Spotted Fever.

The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Forty patients were evaluated (23 male; mean age, 39.87 years); 13 patients were aged <14 years. Seventeen patients received clarithromycin, and 23 received doxycycline or josamycin. The interval between the onset of symptoms and the start of treatment was 4.04 ± 1.70 days in the clarithromycin group versus 4.11 ± 1.60 days in the doxycycline/josamycin group (P = not significant [NS]). Time to the disappearance of fever after treatment was 2.67 ± 1.55 days in the clarithromycin group versus 2.22 ± 1.35 days in the doxycycline/josamycin (P = NS). The symptoms had disappeared at 4.70 ± 2.25 days in the clarithromycin group versus at 4.75 ± 3.08 days in the doxycycline/josamycin (P = NS). There were no adverse reactions to treatment or relapses in either group. In conclusion, clarithromycin is a good alternative to doxycycline or josamycin in the treatment of MSF.

Coinfection with "Rickettsia sibirica subsp. mongolotimonae" and Rickettsia conorii in a Human Patient: a Challenge for Molecular Diagnosis Tools.

Rickettsioses are zoonoses transmitted by vectors. More than one agent can coexist in vectors. Although vectors may transmit more than one microorganism to humans, information on dual infections is scarce. We present a case of a patient with an atypical rickettsiosis diagnosis in whom two species of Rickettsia were detected.

Clinical progression of severely immunosuppressed HIV-infected patients depends on virological and immunological improvement irrespective of baseline status.

OBJECTIVES: The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART. METHODS: This study included naive patients from the PISCIS Cohort with CD4 <200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged >18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders. RESULTS: 2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease progression was found in patients who reached both immunological and viral responses during follow-up, regardless of their baseline situation (1.9% in baseline CD4 >100 cells/mm(3) and viral load <5 log copies/mL; 2.3% in baseline CD4 ≤100 cells/mm(3) and/or viral load >5 log copies/mL). Achieving a CD4 count ≥200 cells/mm(3) was the main predictor of decreased progression to AIDS/death. In those not reaching this CD4 threshold, virological response reduced disease progression by half. CONCLUSIONS: Even in the worse baseline scenario of CD4 ≤100 cells/mm(3) and high baseline viral loads, positive virological and immunological responses were associated with dramatic decreases in progression.

Shell-vial culture and real-time PCR applied to Rickettsia typhi and Rickettsia felis detection.

Murine typhus is a zoonosis transmitted by fleas, whose etiological agent is Rickettsia typhi. Rickettsia felis infection can produces similar symptoms. Both are intracellular microorganisms. Therefore, their diagnosis is difficult and their infections can be misdiagnosed. Early diagnosis prevents severity and inappropriate treatment regimens. Serology can't be applied during the early stages of infection because it requires seroconversion. Shell-vial (SV) culture assay is a powerful tool to detect Rickettsia. The aim of the study was to optimize SV using a real-time PCR as monitoring method. Moreover, the study analyzes which antibiotics are useful to isolate these microorganisms from fleas avoiding contamination by other bacteria. For the first purpose, SVs were inoculated with each microorganism. They were incubated at different temperatures and monitored by real-time PCR and classical methods (Gimenez staining and indirect immunofluorescence assay). R. typhi grew at all temperatures. R. felis grew at 28 and 32 °C. Real-time PCR was more sensitive than classical methods and it detected microorganisms much earlier. Besides, the assay sensitivity was improved by increasing the number of SV. For the second purpose, microorganisms and fleas were incubated and monitored in different concentrations of antibiotics. Gentamicin, sufamethoxazole, trimethoprim were useful for R. typhi isolation. Gentamicin, streptomycin, penicillin, and amphotericin B were useful for R. felis isolation. Finally, the optimized conditions were used to isolate R. felis from fleas collected at a veterinary clinic. R. felis was isolated at 28 and 32 °C. However, successful establishment of cultures were not possible probably due to sub-optimal conditions of samples.

Serosurvey of Rickettsia typhi and Rickettsia felis in HIV-infected patients.

Consistent with the effects of HIV on cell-mediated immunity, an increased susceptibility to intracellular microorganisms has been observed. Rickettsiae are obligate intracellular microorganisms. The aim of this study was to examine Rickettsia typhi and Rickettsia felis infections in HIV+ population. Sera of 341 HIV+ patients were evaluated by indirect immunofluorescent assay. Age, sex, residential locality, risk behavior, stage according to criteria of the Center for Disease Control and Prevention, CD4+/CD8+ T cells, Hepatitis B antigen, and Hepatitis C serology were surveyed. Seroprevalences of R. typhi and R. felis infection were 7.6% and 4.4%, respectively. No associations were found between seropositivities and the assessed variables. Findings were similar to those obtained in healthy subjects from the same region.

['Third day intervention': an analysis of the factors associated with following the recommendations on the prescribing of antibiotics]. / La "intervención del tercer día": análisis de los factores asociados al seguimiento de recomendaciones sobre la prescripción de antibióticos.

INTRODUCTION: Stewardship programs on the use of antibiotics usually include interventions based on non-compulsory recommendations for the prescribers. Factors related to the adherence to expert recommendations, and the implementation of these programmes in daily practice, are of interest. METHODS: A randomized, controlled, multicentre intervention study was performed in 32 hospitalization units. Antibiotic prescriptions were evaluated by an infectious disease specialist on the third day. We describe the implementation of the intervention, the factors associated with adherence to recommendations, and the impact of the intervention. RESULTS: A total of 3,192 interventions were carried out. Information sources used to prepare the recommendations varied significantly between centres. A modification was recommended in 65% of cases: withdrawal (47%), change in administration route (26%), change of drugs or number of antibiotics (27%), and change in dose (5%). Simplification of treatment accounted for 75% of all recommendations. Adherence was 68%, with significant differences between hospitals, and higher when the recommendations consisted of a dose adjustment or change of route, during the first intervention period, and also when recommendations were personally commented on, in addition to writing a note in the clinical chart. We did not find any reduction in antibiotic consumption or variation in the incidence of resistant pathogens. CONCLUSIONS: An important proportion of antibiotic prescriptions may be susceptible to improvement, most of them towards simplification. The adherence to the intervention was high, but significant variations at different centres were observed, depending on the type of recommendation, and the study period. Those recommendations that were personally commented on were more followed more than those only written.

All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection.

BACKGROUND & AIMS: We aimed at comparing overall and liver-related mortality rates, observed in HIV positive subjects followed-up in the Cohorts of Spanish Network on HIV/AIDS Research stratified by HCV co-infection status, with the expected mortality of the general population of same age and sex in Spain, for the period 1997 - 2008. METHODS: We estimated standardized mortality ratio (SMR) and excess mortality, comparing death rates from our cohort (globally and by HCV co-infection) with death rates from the general population standardized by sex in 5 year-age bands. RESULTS: Overall, 5914 HIV positive subjects were included, 37.3% of which were co-infected with HCV; 231 deaths occurred, 10.4% of which were liver-related. SMR for all causes mortality for the HIV positive subjects was 5.6 (CI 95% 4.9-6.4), 2.4 (1.9-3.1) for HCV negative subjects and 11.5 (9.9-13.4) for HCV positive ones. Having HCV co-infection and AIDS yielded an SMR of 20.8 (16.5-26.1) and having AIDS and being HCV negative had an SMR of 4.8 (3.5-6.7). SMR for liver-related mortality was 1.8 (0.6-5.7) for HCV negative subjects vs. 22.4 (14.6-34.3) for HCV positive ones. Overall, both mortality rates as SMR and excess mortality rates were higher for injecting drug users (IDUs) than men having sex with men (MSM) and heterosexuals, patients with AIDS, with and without cART and for subjects included between 1997 and 2003. CONCLUSIONS: There was an excess of all-cause and liver-related mortality in our cohorts compared with the general population. Furthermore, HCV co-infection in HIV positive patients increased the risk of death for both all causes and liver-related causes.

[Cardiovascular risk in human immunodeficiency virus-infected patients in Spain. CoRIS cohort, 2011]. / Riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana en España. Cohorte CoRIS, 2011.

INTRODUCTION: Current information on cardiovascular risk (CVR) in HIV-infected patients in Spain is limited. METHODS: An analysis was made of a prospective multicentre cohort of Spanish HIV-infected patients (CoRIS) between January-2010 and July-2011. CVR was evaluated using Framingham, REGICOR and SCORE equations. RESULTS: The study included 1019 patients (76% males, mean age 40 years) recruited from 13 hospitals belonging to 10 autonomous communities in Spain. Almost two-thirds (65.4%) of patients were on antiretroviral therapy (ART), 36.7% with non-nucleoside analogs, 24% with protease inhibitors (PIs) (52% with atazanavir/r or darunavir/r) and 4,6% with raltegravir. More than half (56.2%) of the patients had an HIV viral load <50 copies/ml. Smoking prevalence was 46%, HDL cholesterol (HDL-C) <40mg/dl 36.1%, total cholesterol (total-C) >200mg/dl 27.8%, age >45years 27.2%, metabolic syndrome 11.5%, hypertension 9.4%, cocaine use 7%, and diabetes 2.9%. ART was associated with higher total-C and LDL-C concentrations, although also higher HDL-C and lower total-C/HDL-C ratio; patients receiving PIs boosted with a high ritonavir dose showed higher total-C levels and higher total-C/HDL-C ratio. According to Framingham cardiovascular, and coronary, REGICOR, and SCORE equations, 15.2%, 6.4%, 4.2% and 3.9% of patients, respectively, were classified as having moderate or high CVR. CONCLUSION: In HIV-infected patients from CoRIS, prevalence of modifiable CVR factors is still high. Commonly used scores identify a relatively low number of patients with high CVR.

Association of Patients' Geographic Origins with Viral Hepatitis Co-infection Patterns, Spain.

To determine if hepatitis C virus seropositivity and active hepatitis B virus infection in HIV-positive patients vary with patients' geographic origins, we studied co-infections in HIV-seropositive adults. Active hepatitis B infection was more prevalent in persons from Africa, and hepatitis C seropositivity was more common in persons from eastern Europe.

Comparative accuracy of 3 monoclonal stool tests for diagnosis of Helicobacter pylori infection among patients with dyspepsia.

BACKGROUND: Well-devised studies comparing new but different monoclonal fecal tests for diagnosing Helicobacter pylori infection are scarce. The objective of this study was to compare the diagnostic accuracy of 3 monoclonal stool tests: 2 rapid in-office tools-RAPID Hp StAR and ImmunoCard STAT! HpSA-and an enzyme immunoassay test-Amplified IDEIA Hp StAR-for diagnosing H. pylori infection prior to eradication treatment. METHODS: Diagnostic reliability was evaluated in 199 untreated consecutive patients with dyspeptic symptoms. The gold standard for diagnosing H. pylori infection was defined as the concordance of the rapid urease test, histopathology, and urea breath test. Readings of immunochromatographic tests were performed by 2 different observers. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated. Sensitivity and specificity were compared using the McNemar test. RESULTS: The sensitivity and specificity of Amplified IDEIA Hp StAR were 90% and 89%, respectively. This enzyme immunoassay test was significantly more sensitive than ImmunoCard STAT! HpSA and more specific than RAPID Hp StAR. The sensitivity and specificity of RAPID Hp StAR were 91% and 80%, respectively, according to observer 1, and 92% and 76%, respectively, according to observer 2. It was significantly more sensitive and less specific than ImmunoCard STAT! HpSA. The sensitivity and specificity of ImmunoCard STAT! HpSA were 69% and 90%, respectively, according to observer 1, and 74% and 89%, respectively, according to observer 2. CONCLUSIONS: Amplified IDEIA Hp StAR seems to be the most accurate stool test for diagnosing H. pylori for patients with dyspeptic symptoms. The currently available in-office tests obtain slightly less reliable results.

Accuracy of monoclonal stool tests for determining cure of Helicobacter pylori infection after treatment.

BACKGROUND: Studies comparing new monoclonal fecal tests for evaluating cure of Helicobacter pylori infection after treatment are scarce. The objective was to compare the diagnostic accuracy of three monoclonal stool tests: two rapid in-office tools -RAPID Hp StAR and ImmunoCard STAT! HpSA - and an EIA test - Amplified IDEIA Hp StAR. MATERIALS AND METHODS: Diagnostic reliability of the three tests was evaluated in 88 patients at least 8 weeks after H. pylori treatment. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated. RESULTS: All tests presented similar performance for post-eradication testing. Sensitivity for detecting persistent infection was 100% for both Amplified IDEIA and RAPID Hp StAR and 90% for ImmunoCard STAT! HpSA. Respective specificities were 94.9%, 92.3-93.6% and 94.9%. Negative predictive values were very high (100%, 100% and 98.7% respectively). But positive predictive values were lower, ranging from 62.5 to 71.4%. CONCLUSION: All monoclonal fecal tests in this series presented similar performance in the post-treatment setting. A negative test after treatment adequately predicted cure of the infection. However, nearly a third of tests were false positive, showing a poor predictive yield for persistent infection.

Accuracy of diagnostic tests for Helicobacter pylori: a reappraisal.

BACKGROUND: Despite many changes, no large studies comparing the different diagnostic tests for Helicobacter pylori have been performed in the past 10 years. In this time, monoclonal stool antigen immunoassays and in-office 13C-urea breath tests (UBTs) have appeared. The aim of this study was to evaluate the accuracy of invasive and noninvasive tests in a large series of dyspeptic patients. METHODS: A total of 199 dyspeptic patients who had not previously been treated for H. pylori infection were prospectively enrolled. Noninvasive analyses included a commercial infrared-based UBT and a commercially available stool test. Biopsy-based tests included histological examination and a rapid urease test. A patient was considered to be infected when at least 2 test results were positive. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated. The test results were compared using the McNemar test. RESULTS: Rates of positive test results were similar (54%) for the rapid urease test, histopathological examination, and the stool test. By contrast, 75% of UBT results were positive, and the UBT was associated with a very low specificity (60%). For this reason, the delta cutoff value for the UBT was recalculated as 8.5%. Sensitivities and specificities with this new cutoff value were 95% and 100%, respectively, for the rapid urease test; 94% and 99%, respectively, for histopathological examination; 90% and 93%, respectively, for the stool test; and 90% and 90%, respectively, for the UBT. CONCLUSIONS: Histological examination and rapid urease testing showed excellent diagnostic reliability. The stool test seems to be a good, noninvasive alternative to endoscopy-based tests. By contrast, the infrared-based UBT evaluated in our study showed a lower than expected performance, which was partially corrected when the cutoff value for the test was recalculated.

Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality.

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

Seroprevalence of Bartonella spp. infection in HIV patients in Catalonia, Spain.

BACKGROUND: Although the first clinical descriptions of Bartonella infection were associated with immunocompromised patient with bacillary angiomatosis, we currently know that this organism is directly involved in diseases affecting a large number of patients, regardless of their immune status. Cat scratch disease, hepatic peliosis, and some cases of bacteraemia and endocarditis, are directly caused by some species of the genus Bartonella. The purpose of this study was to determinate the prevalence of IgG antibodies against Bartonella henselae and B. quintana in HIV patients and to identify the epidemiological factors involved. METHODS: Serum samples were collected from HIV patients treated at Hospital de Sabadell. Antibodies to B. henselae and B. quintana from 340 patients were examined by indirect immunofluorescence assay (IFA). Significance levels for univariate statistical test were determined by the Mann-Whitney U test and chi2 test. RESULTS: Of 340 patients, 82 were women and 258 men, with a median age of 42.21 +/- 10.35 years (range 16-86 years). Seventy-six (22.3%) patients reacted with one or more Bartonella antigens. Of all the factors concerning the seroprevalence rate being studied (age, sex, intravenous drugs use, alcohol consumption, CD4 levels, AIDS, HCV, HBV, residential area), only age was statistically significant. CONCLUSION: A high percentage of HIV patients presents antibodies to Bartonella and is increasing with age.

Detection of Rickettsia massiliae/Bar29 and Rickettsia conorii in red foxes (Vulpes vulpes) and their Rhipicephalus sanguineus complex ticks.

To determine the prevalence of exposure to Rickettsia massiliae/Bar29 and Rickettsia conorii in wild red foxes, we collected blood samples and ticks from 135 foxes shot in different game reserve areas in Catalonia. To detect SFG rickettsia in Rhipicephalus sanguineus complex ticks collected from the foxes, we used real-time polymerase chain reaction (PCR) to screen for ompA gene and a tick-borne bacteria flow chip technique based on multiplex PCR. Serum samples were positive for antibodies against spotted fever group (SFG) rickettsiae in 68 (50.3%). Molecular techniques identified R. massiliae in 107 ticks, R. aeschlimannii in 3 ticks, and R. slovaca in one tick; no R. conorii was identified in any of the ticks analyzed. We conclude that red foxes can carry ticks with SFG rickettsia.

[HIV in Spain 2017: policies for a new management of chronicity beyond virological control]. / VIH en España 2017: políticas para una nueva gestión de la cronicidad más allá del control virológico.

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms.

El análisis de las bases de datos disponibles relacionadas con VIH/SIDA confirma un cambio de paradigma en la esperanza de vida del paciente: ahora el VIH se ha convertido en una enfermedad crónica, con la que los pacientes están envejeciendo. No obstante, este avance se acompaña de una contraparte negativa: debido al incremento en el número de años de vida ganados, se da una prevalencia de comorbilidades mayor a la de la población general y a una edad más temprana. Reducir el riesgo asociado a todas las comorbilidades que puede desarrollar el paciente con VIH/SIDA mientras envejece debe ser hoy en día un objetivo de salud, que se suma a los objetivos tradicionales que hasta ahora formaban parte de la estrategia para reducir el impacto de la infección por el VIH. En el caso específico de la mujer, además es necesario formar a las mujeres peri y postmenopáusicas para incrementar sus habilidades y su motivación para el cuidado de su salud; también es muy importante que se examine el rol que puede tener la terapia de reemplazo hormonal en la reducción de sus síntomas.

Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection.

BACKGROUND: We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved. METHODS: We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter. RESULTS: At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups. CONCLUSIONS: When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.