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Background: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). Methods: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). Results: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. Conclusions: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. Lay Summary: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

Summary Background HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care. Methods An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 – June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions. Results IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p = 0.009), intensive care treatment (66.7vs. 30.6%; OR = 4.54; p = 0.018), and longer median hospitalization (48 days vs. 23; p 6Log10/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p = 0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0 vs. 1446.5; p = 0.023). Conclusion Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of > 6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.

in press Background Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. Methods This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. Conclusions In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of observation was 451 days (IQR 357-488), totaling 5132 py.Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the covid-19 pandemic period.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

BACKGROUND: Many cases of monkeypox have been reported across Europe from early May 2022 onward. Initial publications suggest that nearly all of the affected persons to date have been men who have sex with men (MSM). METHODS: To characterize the German cases, an anonymous questionnaire was sent via the mailing lists of the German AIDS Society (Deutsche AIDS-Gesellschaft, DAIG) and the German Association of Outpatient Physicians for Infectious Diseases and HIV Medicine (Deutsche Arbeitsgemeinschaft ambulant tätiger Ärztinnen und Ärzte für Infektionskrankheiten und HIV-Medizin e.V., DAGNAE). RESULTS: 301 PCR-verified cases had been registered as of 23 June 2022. All of the affected persons were MSM, including 141 (46.7%) with HIV infection and 135 (44.7%) with pre-exposure prophylaxis (PrEP). The great majority of skin lesions were in the anal and genital areas. The most common general symptoms were fever, headache, limb pain, and, often, painfully swollen lymph nodes. Most infections to date have taken a relatively mild course: 5.0% of the patients were hospitalized, and none died. A high frequency of sexually transmitted infections (STI) was noted: only 41.0% of the patients had not been given a diagnosis of an STI in the six months before their monkeypox infection. CONCLUSION: Monkeypox seems to be establishing itself as a new type of STI among MSM. In view of the rising case numbers, there is a need for a rapid information and vaccination campaign in the population at risk. Heightened alertness among physicians is needed as well.

Objectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.Anonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357-488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period.We found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war.

Information on testing units in health care is scarce, particularly the group of late-presenters among the HIV-first diagnoses is still a challenge in Germany.Analysis of the impact of testing units on and reasons for the prevalence of HIV-first diagnoses and late presentation, taking 2014 for illustrative purposes.Cross-sectional analysis of all individuals, treated in the Network HIV-Regional who were first diagnosed with HIV in 2014; patient characteristics, demographic and clinical data, including information on HIV testing were collected retrospectively and in a decentralised manner, pseudonymized and statistically evaluated.A total of 971 individuals with HIV-first diagnosis from 31 specialised care centres throughout Germany (15 hospitals, 16 private practices) represented 27.5% of all National HIV-first diagnoses -registrations from Robert Koch Institute for 2014, with similar results for CD4-cell count and HIV-transmission risk. The most common test site was a hospital (34.8%), followed by the office of a family doctor (19.6%) and medical specialist (16.1%). If the first diagnosis was established in hospital, then the patients were on average older than those tested on an ambulant care basis (42 vs. 37 years, p=0.001); moreover, the HI-viral load was higher (585 vs. 270 thousand copies/mL, p0.001) and the CD4-cell count lower (265 vs. 414/µL, p0.001). In 208/971 individuals with first diagnosis, at least one AIDS-defining disease was found, most frequently pneumocystis-pneumonia (43.8%), candidiasis (36.5%) and Kaposi sarcoma (10.6%). A regional comparison revealed that in eastern Germany, for first diagnosed HIV-patients were younger, had a higher HIV-RNA viral load and also more often clinical AIDS.This analysis of HIV-Regional for 2014 enables a deeper insight into HIV first diagnoses, on the eve of the introduction of important prevention tools in Germany, e. g., HIV home testing and pre-exposure prophylaxis. This cross-sectional analysis was representative for Germany and underscores the importance of specialised hospitals, in particular for eastern Germany, and furthermore the involvement of late-presenters into HIV health care.Über die qualitative Bedeutung der testenden Zentren im Gesundheitswesen ist wenig bekannt, gleichzeitig stellen die Late-Presenter eine immer noch große Gruppe bei den HIV-Erstdiagnosen.Analyse des Einflusses von Testzentren und -grund auf die Prävalenz von HIV-Erstdiagnosen und Late-Presentation, exemplarisch für das Jahr 2014.In einer Querschnittsstudie wurden zu allen im Netzwerk HIV-Regional Behandelten mit Erstdiagnose HIV im Jahr 2014 retrospektiv, pseudonymisiert und dezentral klinische und demographische Patienten-Charakteristika inklusive Angaben HIV-Test gesammelt und zentral statistisch ausgewertet.971 Individuen mit Erstdiagnose HIV aus 31 spezialisierten Versorgungszentren in ganz Deutschland (15 Kliniken, 16 Praxen) repräsentieren einen Anteil von 27,5% aller HIV-Erstdiagnosemeldungen des Robert-Koch-Instituts für 2014, mit ähnlichen Ergebnissen für CD4-Zellzahl und HIV-Übertragungsrisiko. Häufigster Testort war das Krankenhaus (34,8%), gefolgt vom Hausarzt (19,6%) und Facharzt (16,1%). Wurde die Erstdiagnose in der Klinik gestellt, dann waren die Betroffenen im Mittel älter als ambulant getestete (42 vs. 37 Jahre, p=0,001), außerdem fand sich eine höhere HI-Viruslast (585 vs. 270 Tsd. Kopien/mL, p0,001) und niedrigere CD4-Zellzahl (265 vs. 414/µL, p0,001). Bei 208/971 HIV-positiv getesteten fand sich mindestens eine AIDS-definierende Erkrankung, am häufigsten die Pneumocystis-Pneumonie (43,8%), Candidiasis (36,5%) und Kaposi-Sarkom (10,6%). Im regionalen Vergleich fand sich bei ostdeutschen Erstdiagnostizierten ein jüngeres Lebensalter, eine höhere HIV-RNA und häufiger das Vollbild AIDS.Die HIV-Regional-Analyse zum Jahr 2014 erlaubt exemplarisch einen tieferen Einblick in die HIV-Erstdiagnosen am Vorabend der Einführung wichtiger Präventionsmaßnahmen in Deutschland, z. B. HIV-Heimtests und die Prä-Expositionsprophylaxe. Diese repräsentative Stichprobe unterstreicht die Bedeutung spezialisierter Kliniken für die HIV-Versorgungsstruktur, besonders für Ostdeutschland und allgemein für die Einbindung sogenannter Late-Presenter ins Gesundheitswesen.

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence and prevalence of infections with HIV, Chlamydia, Gonorrhea, Syphilis, Hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with Chlamydia/Gonorrhea and Syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Logistic regression was used to analyze risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), PrEP indication 98.6% men who have sex with men (MSM). Duration of PrEP use were 5132 py; median duration 451 days (IQR 357-488).Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for Chlamydia, 23.7/100py for Gonorrhea, 10.1/100py for Syphilis and 55.4/100py for any STI and decreased significantly. 65.5% of Syphilis, 55.6% of Chlamydia and 50.1% of Gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for Chlamydia/Gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for Chlamydia/Gonorrhea and Syphilis.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were likely influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Introduction Despite increased use of pre-exposure prophylaxis (PrEP) in Germany, HIV infection rates are not declining and little is known about how this prevention method affects the prevalence of sexually transmitted infections (STI) among men who have sex with men (MSM). Aim We studied, in a large multicentre cohort, STI point prevalence, co-infection rates, anatomical location and influence of PrEP. Methods The BRAHMS study was a prospective cohort study conducted at 10 sites in seven major German cities that enrolled MSM reporting increased sexual risk behaviour. At screening visits, MSM were tested for Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum (TP), and given a behavioural questionnaire. With binomial regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the association of PrEP and STI. Results We screened 1,043 MSM in 2018 and 2019, with 53.0% currently using PrEP. At screening, 370 participants (35.5%) had an STI. The most common pathogen was MG in 198 (19.0%) participants, followed by CT (n = 133; 12.8%), NG (n = 105; 10.1%) and TP (n = 37; 3.5%). Among the 370 participants with at least one STI, 14.6% (n = 54) reported STI-related symptoms. Infection prevalence was highest at anorectal site (13.4% MG, 6.5% NG, 10.2% CT). PrEP use was not statistically significant in adjusted models for STI (PR: 1.10; 95% CI: 0.91–1.32), NG/CT, only NG or only CT. Conclusions Prevalence of asymptomatic STI was high, and PrEP use did not influence STI prevalence in MSM eligible for PrEP according to national guidelines.

Background HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM. Methods From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months. Results Among 1017 participants with median age 33 (interquartile range 28–39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing. Conclusion Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.

BACKGROUND In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through week 48. Here, we present long-term efficacy and safety outcomes through week 144 of the DRIVE-SHIFT trial. METHODS This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at day 1 [immediate switch group (ISG); n = 447] or week 24 [delayed switch group (DSG); n = 209]. Nine ISG participants who completed week 48 but did not enter extension-1 were excluded from week 144 efficacy analyses. RESULTS At week 144, HIV-1 RNA

Background Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH). Methods DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA, The DUALIS phase-III study demonstrated non-inferiority of an effective and safe switch to dolutegravir combined with boosted darunavir (2DR) in suppressed people living with HIV as compared to continue 2 nucleoside reverse transcriptase inhibitors in combination with boosted darunavir (3DR).

Introduction Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. Methods Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. Results Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. Conclusions This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

5053 Background: Previous studies showed that men with HIV-associated germ cell cancer (HIV-GCC) have a similar cancer-free outcome compared with their HIV-negative counterparts. However, the overall survival (OS) was inferior and little data is available on treatment and outcome of HIV-GCC in the era of combined antiretroviral therapy (cART). Methods: Men living with HIV aged ≥ 18 years (yrs) with a diagnosis of histologically proven GCC made from 01/1996 to 07/2018 were included. Primary outcomes were OS and progression-free survival (PFS). Secondary outcomes included characteristics of GCC and HIV-infection, treatment and causes of death. Results: Data of 89 men from 23 institutions and 6 countries with a total of 92 HIV-GCC (2 synchronous and 1 metachronous bilateral GCC) were analysed, among them 64 (70%) seminomas and 28 (30%) nonseminomas. 10/89 (11%) cases were primary extragonadal GCC. Median age was 36 yrs (range, 22-52) and median time from HIV to GCC diagnosis was 5 yrs (range, 0-29). Median CD4 count at GCC diagnosis was 420 cells/µl (range, 3-1503) and 83% of pts were on cART. Stage I disease was found in 44/80 (55%) gonadal GCC (metachronous bilateral case included). Of 46 cases with stage II/III/extragonadal GCC 78%, 17% and 4% were assigned to the IGCCCG good, intermediate and poor prognosis group, respectively. Of the 44 stage I cases, 22 (50%) were followed by active surveillance, and 11 (25%) received adjuvant chemotherapy (CT) or radiotherapy. Relapses occurred in 14 pts (6 from stage I, 8 in pts primary disseminated GCC) and CT was applied to 13/14 pts, of which 3 received high-dose CT. Overall, 12/89 (13%) pts have died. Causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3) and other (n = 4). After a median follow-up of 6.5 yrs (range, 0.3-20.9), the 5- and 10-year PFS rate was 81% and 73%, and the 5- and 10-year OS rate was 91% and 85%, respectively. There were no significant differences between the good and intermediate prognosis group or between pts with CD4 counts < 200/µl or ≥ 200/µl. Conclusions: The 5- and 10-year PFS and OS rates of men with HIV-GCC are similar to those reported for HIV-negative GCC. Pts with HIV-GCC should remain on cART and be managed in an identical fashion to HIV-negative pts.

OBJECTIVES Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study. METHODS In order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir-containing combinations. RESULTS The overall rate of virological suppression to < 50 HIV-1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96. CONCLUSIONS These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.

OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. METHODS: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. RESULTS: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA < 400 copies/mL. CONCLUSIONS: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.

Background Here, we aimed to evaluate regional differences in all-cause, AIDS- and non-AIDS-related mortality in HIV-positive men and women started on combination antiretroviral therapy (cART) in Europe, Canada and the US. Methods The ART Cohort Collaboration (ART-CC) combines 19 cohorts of individuals started on cART in Europe and North America (NA). We analysed patients infected via injecting drug use (IDU) or heterosexual sex using Cox proportional hazards models. Results A total of 32,443 European (45.9% women), 1,162 (32.5% women) Canadian and 2,721 (15.5% women) US patients were included. In Europe and NA, women were younger, more likely to have acquired HIV heterosexually, be AIDS-free and have higher CD4+ T-cell counts and lower HIV-1 RNA at baseline. European women had lower rates of all-cause (adjusted hazard ratio: 0.76; 95% CI 0.68, 0.84) and non-AIDS mortality (0.67; 0.57, 0.78) than men, but AIDS-mortality rates were similar (0.90; 0.75, 1.09). Women had lower mortality due to non-AIDS infections (0.6 versus 1.3 per 1,000 person-years), liver diseases (0.4 versus 1.7), non-AIDS malignancies (0.6 versus 2.0) and cardiovascular diseases (0.6 versus 1.0). Between-sex differences in all-cause mortality were larger in heterosexuals (0.70; 0.61, 0.80) than in IDU (0.88; 0.73, 1.05; interaction P-value =0.043). No sex differences in all-cause mortality were found in Canada (hazard ratio women 1.13; 0.82, 1.56) or US (hazard ratio women 1.12; 0.79, 1.58). Conclusions The increasing importance of non-AIDS mortality is leading to emergent sex differences among HIV-positive patients in Europe, as in the general population. Despite the better clinical characteristics at cART initiation, women in NA had similar mortality to men.

Summary Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

To evaluate the treatment outcome of antiretroviral therapy, depending on the use and utility of a concept of resistance-guided switch, patients from the Frankfurt HIV cohort have been followed for 24 weeks. If available, prior resistance data have been evaluated and patients were grouped into their expected viral response. The data of 354 patients were thus analyzed, taking into account the Genotypic Sensitivity Score of the administered medication (> or ≤ 2). When looking at the proportion of patients who achieved a viral load of less than 50/ml, the response rates differed significantly better for patients with a favourable resistance scoring as compared to an unfavourable one (71.9 % as compared to 56.0%, p = 0.008). Interestingly, patients with a favourable resistance score also showed a better immunological response, as measured by median CD4 cell count of 391/μl (Interquartal Range: 250 – 530/μl) against 287/μl (Interquartal Range: 174 – 449/μl) and a larger total increase of 141/μl against 38/μl. A significant virological and immunological benefit could be demonstrated for patients of a cohort with resistance-guided antiretroviral therapy adjustments.

OBJECTIVES The rapid early-phase decay of plasma HIV-1 RNA during integrase inhibitor-based therapy is not fully understood. The accumulation of biologically active episomal HIV-1 cDNAs, following aborted integration, could contribute to antiviral potency in vivo. METHODS This prospective, controlled clinical observation study explored raltegravir's impact on the dynamics of HIV-1 RNA in plasma, and concentrations of total HIV-1 cDNA, episomal 2-long terminal repeat (LTR) circles and HIV-1 integrants in peripheral blood mononuclear cells (PBMC). Individuals starting therapy with two nucleoside reverse transcriptase inhibitors plus either raltegravir (raltegravir group; n = 10 patients) or boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitor (control group; n = 10 patients) were followed for 48 weeks. RESULTS Suppression of HIV-1 RNA (

Objective Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome. Methods Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation. Results None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection. Conclusions Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data.

Background Doravirine is a novel, non-nucleoside reverse-transcriptase inhibitor (NNRTI) that has demonstrated efficacy in two Phase 3 trials in treatment-naïve adults with HIV-1. Methods This open-label, active-controlled, noninferiority (NI) trial evaluated a once-daily single-tablet regimen of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) vs. continuation of current therapy in adults with HIV-1 virologically suppressed for ≥6 months on a stable regimen of two NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or NNRTI. Participants with screening HIV-1 RNA Results A total of 670 participants (447 ISG, 223 DSG) were treated and included in the analyses; 84.5% were male, 76.4% were white, and mean age was 43.3 years. At Week 24, 93.7% (419/447) of ISG vs. 94.6% (211/223) of DSG had HIV-1 RNA Conclusion A once-daily single-tablet regimen of DOR/3TC/TDF demonstrated non-inferior efficacy and acceptable safety compared with continuing therapy, and is an option for maintaining viral suppression in patients considering a change in therapy. Disclosures P. Kumar, Merck, Pfizer, Janssen,: Grant Investigator and Shareholder, Research grant. GSK, Gilead, Teratechnologies, TaiMed,: Grant Investigator, Scientific Advisor and Shareholder, Consulting fee and Research grant. J. M. Molina, Merck GIlead ViiV Janssen Teva: Ad Board and Speaker’s Bureau, Consulting fee. Gilead Sciences: Grant Investigator, Research support. G. Rizzardini, ViiV, Gilead Science, MSD, Angelini, and Abbvie: Board Member and Speaker’s Bureau, Speaker honorarium. Gliead, ViiV, and MSD: Research Contractor, Research grant. P. Cahn, Abbvie: Grant, Research grant. Merck: Grant, Advisory Board. ViiV Healthcare: Grant, Advisory Board. M. Bickel, Merck & Co., Inc.: Research Contractor, Research grant. Y. Zhou, Merck & Co., Inc.: Employee, Salary. C. Morais, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, May hold stock/stock options in the company and Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. P. Sklar, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.: Employee and Shareholder, Salary. G. J. Hanna, Merck Sharp & Dohme, a subsidiary of Merck & Co., inc.: Employee and Shareholder, May hold stock/stock options in the company. and Salary. C. Hwang, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, Salary. W. Greaves, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee, May hold stock/stock options within the company.

Objectives The renal elimination of tenofovir (TFV) may be subject to renal drug−drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug−drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. Methods A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. Results Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). Conclusions Drug−drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.

Etravirine is currently approved for HIV treatment-experienced patients at a dose of 200 mg twice daily. The long terminal elimination half-life of etravirine should support once-daily dosing.In the double-blind 48-week SENSE trial, 157 antiretroviral treatment-naïve patients were randomly assigned to receive etravirine 400 mg once daily (n = 79) or efavirenz 600 mg once daily (n = 78), plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). Sparse sampling for etravirine plasma concentrations was conducted during the 48-week trial. Area under the curve over the dosing interval (AUC24h) and trough concentration (C0h) were estimated using a population pharmacokinetic model and compared with previous results using the 200-mg twice-daily dosage. The relationship between etravirine AUC24h and C0h with efficacy and safety was also assessed.By week 48, the percentage of patients in the etravirine arm with HIV RNA50 copies/ mL was 75.9% in the intent-to-treat switch equals failure analysis and 92.3% in the on-treatment analysis; no patient developed genotypic or phenotypic resistance to NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) after virologic failure. Seventy-one subjects had evaluable etravirine pharmacokinetics. The median (interquartile range) of etravirine AUC24h and C0h were 12,447 (8,261-15,652) ng•h/mL and 330 (188-472) ng/mL, respectively. There was no correlation between etravirine exposure and virologic response or adverse events.In the SENSE trial, etravirine 400 mg once daily achieved similar exposures to historical reference data on etravirine when dosed at 200 mg twice daily. There was no apparent relationship between the pharmacokinetics of etravirine and virologic response or adverse events.

HIV controllers are a valuable source for the identification of HIV-neutralizing antibodies, as chronic infection over decades allows extensive affinity maturation of antibodies for improved Ag recognition. We analyzed a small cohort of elite controllers (ECs) for HIV-neutralizing antibodies using a panel of standardized HIV-1 pseudovirions on TZM-bl cells. An HIV-1 Env-tailored phage display library was generated to select epitopes targeted by neutralizing antibodies in the EC26 plasma sample showing the broadest neutralizing activity. Selected Env fragments were mostly allocated to the membrane proximal external region of gp41. After preabsorbing the EC26 plasma with the selected phage EC26-2A4, we achieved 50% depletion of its neutralizing activity. Furthermore, antibodies affinity-purified with the EC26-2A4 epitope from EC26 plasma showed neutralizing activity, proving that the selected phage indeed contains an epitope targeted by neutralizing plasma antibodies. Epitope fine mapping of the purified plasma antibodies on peptide arrays identified a new epitope overlapping, but clearly distinct, from the prominent 2F5 epitope. Of note, the purified antibodies did not show autoreactivity with cardiolipin, whereas low reactivity with phosphatidylserine comparable to mAb 2F5 was observed. Thus, this new epitope represents a promising candidate for further analysis in view of HIV vaccine development.

There are concerns about central nervous system (CNS)-replication of HIV-1 in patients on boosted protease inhibitors. Purpose of this study was to compare HIV-1 viral loads (VLs) from patients treated with only boosted dual protease inhibitor (bdPI), versus combination antiretroviral therapy (cART group), containing two nucleoside analogue reverse transcriptase inhibitors (NRTI) and a third partner. All patients from a large German HIV-treatment cohort with available medication, clinical and demographic data, including results from simultaneous HIV-1 viral load (VL) assessments in cerebrospinal fluid (CSF) and blood plasma, were retrospectively evaluated as controlled cross-sectional study. CSF had been obtained from patients with variable neurological symptoms during 2005–2014. Statistical analysis comprised nonparametric tests, regression and correlation techniques accounting for undetectable quantifications. Statistical analysis comprised nonparametric tests, regression and correlation techniques accounting for undetectable quantifications. Overall, 155 patients were evaluable (bdPI: 24; cART: 131). At time of CSF-collection, both groups were comparable in age, gender, CD4-cell counts, or primary HIV-transmission risks, though bdPI patients were clinically more advanced. The proportion of patients with undetectable HIV-1 (

Objectives Renal disease is a common and serious complication in HIV-infected patients. Methods A retrospective cohort analysis for the period 1989–2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989–1996 [pre-highly active antiretroviral therapy (HAART)], 1997–2003 (early HAART) and 2004–2010 (late HAART). Results Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years (PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3–10.3; P

Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always50 copies/ml (1), 50-199 copies/ml (2), 200-499 copies/ml (3) and ≥500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm(3), HIV-1 RNA was 5.13 Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients were assigned by 43, 30, 7 and 20 % to groups 1-4. Median observation time was 136 weeks (range: 38-304); at weeks 48/96, the CD4-cell gains for groups 1-4 were +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data in a linear fixed effect model, ascending CD4 slopes were continuously increasing for group 1, similarly for 2 and clearly decreasing for 3-4 (p = 0.0006). Of 25 individuals from group 4, patient number with major IAS-USA protease mutations increased from 5 to 10 before and after failing PI therapy, whereas minor mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell increases through week 96 were similar for patients at always undetectable or with detection of low viral load. Viral detection200 copies/ml was associated with decreasing CD4-cell slopes and emergence of major mutations, supporting this as benchmark for virological failure definition on PI therapy.

Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and ≥ 4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.

Background: There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown.Methods: This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group.Results: Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01).Conclusion: Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.

BACKGROUND To determine the rate of seroconversion after 2 doses of a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)-infected patients (ClinicalTrials.gov NCT01017172). METHODS Diagnostic study of adult HIV-1-infected patients scheduled for H1N1 influenza A vaccination. Blood samples where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and a ≥ 4-fold increase in AB titer 21 days after vaccination. RESULTS One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed. The rate of seroconversion was 68.2% (95% confidence interval, 59.6-75.9) after the first dose and 91.9% (95% confidence interval, 85.9-95.9) after the second dose. Patients who did not seroconvert had a lower mean nadir CD4 cell count (± standard deviation; 81 ± 99 vs 190 ± 148 cells/μL; P = .006), had a longer duration of HIV infection (± standard deviation; 13.1 ± 5.9 vs 8.8 ± 6.8 years; P = .04), and were more likely to have an AB titer ≥ 1:40 before vaccination (4% vs 55%; P