Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results: The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions: In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice. Clinical Trials Registration: NCT04707326.

Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.

[A man with cervical lymph node swelling]. / Een man met een zwelling in de hals.

A 48-year-old HIV-positive patient presented at the otorhinolaryngology department with a growing mass on the left side of his neck, fever and night sweats. Biopsy demonstrated a granulomatous, necrotizing inflammation. After extensive additional testing, PCR on lesion punctate material was positive for Chlamydia trachomatis, yielding a diagnosis of cervical lymphogranuloma venereum.

Neurosyphilis mimicking giant cell arteritis both clinically and microscopically.

Temporal arteritis is usually caused by giant cell arteritis (GCA). However, inflammation of the temporal artery can also occur secondary to autoimmune diseases or infections.We present a remarkable case of a man in his 70s with biopsy proven temporal arteritis, who was later diagnosed with meningovascular neurosyphilis. The presentation of an acute onset monocular vision loss with inflammation of the temporal artery on biopsy appeared a GCA, misleading the physicians, as it turned out to be a manifestation of neurosyphilis.

[COVID-19: patient zero in the Netherlands]. / COVID-19: patiënt nul in Nederland.

BACKGROUND: Since December 2019, the world is captivated by SARS-CoV-2, a new coronavirus that shows a lot of similaritieswith previous coronaviruses such as SARS and MERS. Although it was initially seen mainly in China and the surrounding countries, now it also reached Europe, where a large region in northern Italy, in particular, encountered many infections. CASE DESCRIPTION: Here we describe the first Dutch patient with COVID-19, a 56-year-old man whose infection appeared to be related to a trip to Northern Italy one week before presentation. In the days that followed, the brother of the patient with whom he had traveled, his wife and daughter also tested positive. CONCLUSION: At the moment much is still unclear and it is particularly important to quickly identify patients with an increased risk of complications and to prevent unrestrained spread in the Netherlands.

[Non-typhoidal Salmonellainfections: not always innocent]. / Non-typhoidale Salmonella-infecties.

Non-typhoidalSalmonellae (NTS) are virulent bacteria that commonly cause gastroenteritis. However, less than 5% of patients infected with NTS develop bacteraemia and metastatic foci of infection. Mortality remains high, despite appropriate use of antibiotic therapy. We present three cases to demonstrate that immunodeficiency - and T-cell dysfunction in particular - is a major risk factor for NTS bacteraemia. All three patients presented with fever and general malaise, while none of them had symptoms of gastroenteritis. Blood cultures revealed the presence of Salmonella enteritidis, but stool cultures were negative. All three patients were diagnosed with vascular infection, for which they were treated with a combination of surgery and antibiotics. The efficiency of NTS clearance depends greatly on successful antigen presentation to T-cells. T-cell dysfunction contributes to the development of bacteraemia. These cases emphasise the importance of recognising extraintestinal complications of NTS infection in immunocompromised patients, particularly those associated with T-cell dysfunction.

Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial.

BACKGROUND: Direct-acting antivirals effectively treat chronic hepatitis C virus (HCV) infection but there is a paucity of data on their efficacy for acute HCV, when immediate treatment could prevent onward transmission. We assessed the efficacy of grazoprevir plus elbasvir treatment in acute HCV infection and investigated whether treatment can be shortened during the acute phase of HCV infection. METHODS: The Dutch Acute HCV in HIV study number 2 (DAHHS2) study was a single-arm, open-label, multicentre, phase 3b trial. Adult patients (≥18 years) with acute HCV genotype 1 or 4 infection (duration of infection 26 weeks or less, according to presumed day of infection) were recruited at 15 HIV outpatient clinics in the Netherlands and Belgium. All patients were treated with 8 weeks of grazoprevir 100 mg plus elbasvir 50 mg administered as one oral fixed drug combination tablet once daily. The primary efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12; HCV RNA <15 IU/mL) in all patients who started treatment. Reinfection with a different HCV virus was not considered treatment failure in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02600325. FINDINGS: Between Feb 15, 2016, and March 2, 2018, we assessed 146 patients with a recently acquired HCV infection for eligibility, of whom 86 were enrolled and 80 initiated therapy, all within 6 months after infection. All patients who initiated treatment completed treatment and no patients were lost to follow-up. 79 (99%, 95% CI 93-100) of 80 patients achieved SVR12. All 14 patients who were infected with a virus carrying a clinically significant polymorphism in NS5A were cured. If reinfections were considered treatment failures, 75 (94%, 86-98) of 80 patients achieved SVR12. Two serious adverse events not considered related to the treatment were reported (traumatic rectal bleeding and low back surgery). The most common adverse event was a new sexually transmitted infection (19 [24%] of 80 patients). The most common reported possibly drug-related adverse events were fatigue (11 [14%] patients), headache (seven [9%] patients), insomnia (seven [9%] patients), mood changes (five [6%] patients), dyspepsia (five [6%] patients), concentration impairment (four [5%] patients), and dizziness (4 [5%] patients), all of which were regarded as mild by the treating physician. No adverse events led to study drug discontinuation. INTERPRETATION: 8 weeks of grazoprevir plus elbasvir was highly effective for the treatment of acute HCV genotype 1 or 4 infection. The ability to treat acute HCV immediately after diagnosis might help physicians to reach the WHO goal of HCV elimination by 2030. FUNDING: Merck Sharp and Dohme and Health-Holland.

Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy.

BACKGROUND: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4+ T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned. METHODS: Study within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4+ T-cells per µL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRISFRENCH) or by a clinical IRIS diagnosis of the physician (IRISCLINICAL). The primary outcomes were the association between INI and the occurrence of IRISFRENCH and IRISFRENCH+CLINICAL in multivariable logistic regression. FINDINGS: 672 patients with a median CD4+ T-cell count of 35 cells per µL were included. Treatment with INI was independently associated with IRISFRENCH as well as IRISFRENCH+CLINICAL (OR 2·43, 95%CI:1·45-4·07, and OR 2·17, 95%CI:1·45-3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRISFRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRISFRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRISFRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p=0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed. INTERPRETATION: In HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters. FUNDING: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment.

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.

Background: Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods: Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years. Results: The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35-.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions: Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

The Value of 18F-FDG PET/CT in Diagnosis and During Follow-up in 273 Patients with Chronic Q Fever.

In 1%-5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18F-FDG PET/CT scan was obtained. Clinical data and results from 18F-FDG PET/CT at diagnosis and during follow-up were collected. 18F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever-related mortality rate in patients with and without vascular infection based on 18F-FDG PET/CT was 23.8% and 2.1%, respectively (P = 0.001). When 18F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18F-FDG PET/CT scans resulted in treatment modification. Conclusion:18F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival.

Etravirine Pharmacokinetics in HIV-Infected Pregnant Women.

BACKGROUND: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. METHODS: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). RESULTS: Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. CONCLUSION: Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. CLINICAL TRIAL REGISTRATION: The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

Chronic Q fever diagnosis­ consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006­2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%)would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice.

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women.

OBJECTIVE: To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. METHODS: HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. RESULTS: Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing. CONCLUSIONS: Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy. CLINICAL TRIALS REGISTRATION: NCT00825929 and NCT000422890.

Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database.

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P=0.004 and 0.010), proven chronic Q fever (P=0.020 and 0.002), vascular chronic Q fever (P=0.024 and 0.005), acute presentation with chronic Q fever (P=0.002 and P<0.001), and surgical treatment of chronic Q fever (P=0.025 and P<0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.

[Neonatal outcomes of prevention of vertical HIV transmission; 15 years of experience in a non-university HIV centre]. / Neonatale uitkomsten van preventie van verticale hiv-besmetting; 15 jaar ervaring in een niet-universitair hiv-centrum.

OBJECTIVE: To evaluate the neonatal outcomes of the policy for the prevention of vertical HIV transmission in a non-university HIV centre. DESIGN: Retrospective, descriptive study. METHOD: We analysed the HIV status of newborns of HIV-positive mothers during pregnancy in the period between 1 January 1995 and 31 December 2010 in St. Elisabeth Hospital, Tilburg, the Netherlands and compared these results with the Dutch HIV monitoring foundation (SHM) registration data. RESULTS: Eighty-seven children from 84 pregnancies and their 71 HIV-positive mothers were included. Compared with SHM data, more women were African, younger at HIV diagnosis and had less resistance to the usual combination antiretroviral therapy (cART). In line with SHM data, the percentage of elective caesarean sections declined in the study period. There were fewer preterm births than in SHM data. There were no significant differences between preterm birth (p = 0.18), SGA (p = 0.25) or congenital abnormality (p = 0.45) and detectable HIV-RNA or cART use during pregnancy. During 10 (12%) pregnancies the mother presented to the HIV centre too late. At the age of 18 months, all 72 tested children were HIV negative. Of the 15 children lost to follow-up, 8 (9%) left to an unknown destination. CONCLUSION: All newborns of HIV-positive mothers were HIV negative, 12% of the HIV-positive mothers presented too late and 9% of the children disappeared from medical control. These results emphasize the importance of better communication between HIV centres, medical services of asylum centres and first-line obstetric care for female asylum seekers and their children.

Report of two in situ reconstructions with a saphenous spiral vein graft of Coxiella burnetii-infected aneurysms of the abdominal aorta.

Coxiella burnetii is a rare cause of vascular infections. Yet, Q fever is endemic in the southern part of The Netherlands. This report describes two patients--from the southern part of The Netherlands--with infected aneurysms of the abdominal aorta caused by Coxiella burnetii. Both patients underwent surgical debridement, in situ reconstruction with a great saphenous vein spiral graft, and a transmesenteric omentumplasty. One patient fully recovered, while the other died due to ischemic complications. A multidisciplinary work-up approach to treat infected abdominal aneurysms is proposed, including adequate surgical treatment and long-term antibiotic administration.

Microbiological challenges in the diagnosis of chronic Q fever.

Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positive Coxiella burnetii PCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.

Abacavir/lamivudine/zidovudine maintenance after standard induction in antiretroviral therapy-naïve patients: FREE randomized trial interim results.

Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.