Implementation of pre-exposure prophylaxis programme in Spain. Feasibility of four different delivery models

Infeccions pel VIH; Factors de risc mèdics; Profilaxi preexposicióInfecciones por VIH; Factores de riesgo médicos; Profilaxis preexposiciónHIV infections; Medical risk factors; Pre-exposure prophylaxisBackground Pre-exposure prophylaxis (PrEP) is an effective and cost-effective strategy for HIV prevention. Spain carried out an implementation study in order to assess the feasibility of implementing PrEP programmes within its heterogeneous health system. Methods Observational longitudinal study conducted on four different types of health-care setting: a community centre (CC), a sexually transmitted infections clinic (STIC), a hospital-based HIV unit (HBHIVU) and a hospital-based STI unit (HBSTIU). We recruited gay, bisexual and other men who have sex with men (GBSM) and transgender women at risk of HIV infections, gave them PrEP and monitored clinical, behavioural PrEP-related and satisfaction information for 52 weeks. We collected perceptions on PrEP implementation feasibility from health-care professionals participating in the study. Results A total of 321 participants were recruited, with 99.1% being GBMSM. Overall retention was 87.2% and it was highest at the CC (92.6%). Condom use decreased during the study period, while STIs did not increase consistently. The percentage of people who did not miss any doses of PrEP during the previous week remained at over 93%. No HIV seroconversions occurred. We observed overall decreases in GHB (32.5% to 21.8%), cocaine (27.5% to 21.4%), MDMA (25.7% to 14.3%), speed (11.4% to 5.7%) and mephedrone use (10.7% to 5.0%). The overall participant satisfaction with PrEP was 98.6%. Health-care professionals’ perceptions of PrEP feasibility were positive, except for the lack of personnel. Conclusions PrEP implementation is feasible in four types of health-care settings. Local specificities have to be taken into consideration while implementing PrEP.This study has been conducted with the resources from the National AIDS Programme ant those from the participating study centers. Gilead donated the drug administered in the study. Donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Some authors are employed by BCN Checkpoint. BCN Checkpoint is a Community Centre run by an NGO. BCN Checkpoint did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of author PC. The specific roles of this author is articulated in the ‘author contributions’ section

Implementation of pre-exposure prophylaxis programme in Spain. Feasibility of four different delivery models.

Pre-exposure prophylaxis (PrEP) is an effective and cost-effective strategy for HIV prevention. Spain carried out an implementation study in order to assess the feasibility of implementing PrEP programmes within its heterogeneous health system. Observational longitudinal study conducted on four different types of health-care setting: a community centre (CC), a sexually transmitted infections clinic (STIC), a hospital-based HIV unit (HBHIVU) and a hospital-based STI unit (HBSTIU). We recruited gay, bisexual and other men who have sex with men (GBSM) and transgender women at risk of HIV infections, gave them PrEP and monitored clinical, behavioural PrEP-related and satisfaction information for 52 weeks. We collected perceptions on PrEP implementation feasibility from health-care professionals participating in the study. A total of 321 participants were recruited, with 99.1% being GBMSM. Overall retention was 87.2% and it was highest at the CC (92.6%). Condom use decreased during the study period, while STIs did not increase consistently. The percentage of people who did not miss any doses of PrEP during the previous week remained at over 93%. No HIV seroconversions occurred. We observed overall decreases in GHB (32.5% to 21.8%), cocaine (27.5% to 21.4%), MDMA (25.7% to 14.3%), speed (11.4% to 5.7%) and mephedrone use (10.7% to 5.0%). The overall participant satisfaction with PrEP was 98.6%. Health-care professionals' perceptions of PrEP feasibility were positive, except for the lack of personnel. PrEP implementation is feasible in four types of health-care settings. Local specificities have to be taken into consideration while implementing PrEP.This study has been conducted with the resources from the National AIDS Programme ant those from the participating study centers. Gilead donated the drug administered in the study. Donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Some authors are employed by BCN Checkpoint. BCN Checkpoint is a Community Centre run by an NGO. BCN Checkpoint did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of author PC. The specific roles of this author is articulated in the ‘author contributions’ section.S

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions: Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions: Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48‐week analysis of the PROTEST study

Introduction: In a previous interim 24‐week virological safety analysis of the PROTEST study [1], initiation of Maraviroc (MVC) plus 2 nucleoside reverse‐transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV‐1 DNA was associated with low rates of virological failure. Here we present the final 48‐week analysis of the study. Methods PROTEST was a phase 4, prospective, single‐arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc‐naïve HIV‐1‐positive adults with HIV‐1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm3 at screening, and median nadir CD4+ counts were 143 cells/mm3. Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty‐two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow‐up, one (1%) developed an ART‐related adverse event (rash), two (3%) died due to non‐study‐related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol‐defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). Conclusions Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV‐1 DNA is associated with low rates of virological failure up to one year

Increasing and sustaining blood-borne virus screening in Spain and Portugal throughout the COVID-19 pandemic: a multi-center quality improvement intervention

BackgroundAround 57,000 people in Spain and Portugal currently living with HIV or chronic hepatitis C are unaware of their infection. The COVID-19 pandemic severely disrupted screening efforts for these infections. We designed an intervention to increase and sustain opportunistic blood-borne virus (BBV) screening and linkage to care (SLTC) by implementing the TEST model.MethodsThe Plan Do Study Act (PDSA) method of quality improvement (QI) was implemented in 8 healthcare organizations (HCOs), including four hospitals, two clusters of community health centers, and two community-based organizations (CBOs). Baseline assessment included a review of BBV SLTC practices, testing volume, and results 12 months before the intervention. Changes in BBV testing rates over time were measured before, during, and after the COVID-19 lockdowns in 2020. A mixed ANOVA model was used to analyze the possible effect on testing volumes among HCOs over the three study periods.InterventionBBV testing was integrated into normal clinical flow in all HCOs using existing clinical infrastructure and staff. Electronic health record (EHR) systems were modified whenever possible to streamline screening processes, implement systemic institutional policy changes, and promote QI.ResultsTwo years after the launch of the intervention in screening practices, testing volumes increased by 116%, with formal healthcare settings recording larger increases than CBOs. The start of the COVID-19 lockdowns was accompanied by a global 60% decrease in testing in all HCOs. Screening emergency department patients or using EHR systems to automate screening showed the highest resilience and lowest reduction in testing. HCOs recovered 77% of their testing volume once the lockdowns were lifted, with CBOs making the fullest recovery. Globally, enhanced screening techniques enabled HCOs to diagnose a total of 1,860 individuals over the research period.ConclusionsImplementation of the TEST model enabled HCOs to increase and sustain BBV screening, even during COVID-19 lockdowns. Although improvement in screening was noted in all HCOs, additional work is needed to develop strong patient linkage to care models in challenging times, such as global pandemics

Microangiopatía trombótica en una paciente con infección por el virus de la inmunodeficiencia humana

ResumenNotificamos un caso de microangiopatía trombótica, caracterizado por un proceso de agregación plaquetaria amenazante para la vida, que presentó afectación multisistémica y rápida evolución en una paciente con infección por el VIH. En este caso exponemos ampliamente los síntomas, la evolución y, finalmente, la necropsia clínica. Esta enfermedad es ahora infrecuente tras la llegada de los antirretrovirales de gran actividad, no obstante, se presenta con síntomas inespecíficos y evoluciona rápidamente a la afectación multisistémica y muerte. En consecuencia, un diagnóstico precoz con base en criterios clínicos y analíticos es fundamental para instaurar el tratamiento adecuado y mejorar la supervivencia.AbstractWe report on a case of thrombotic microangiopathy, defined as an extensive and dangerous intravascular platelet aggregation disorder, which progressed to multisystem involvement in a patient with HIV infection. For this clinical case, we detail the symptoms, evolution and, ultimately, the clinical autopsy. This disease is now uncommon due to the arrival of high-activity antiretroviral drugs; however, it can appear with nonspecific symptoms and rapidly progress to multisystem involvement and death. An accurate diagnosis on the basis of clinical and analytical criteria is essential to starting treatment and improving survival

Microangiopatía trombótica en una paciente con infección por el virus de la inmunodeficiencia humana

Notificamos un caso de microangiopatía trombótica, caracterizado por un proceso de agregación plaquetaria amenazante para la vida, que presentó afectación multisistémica y rápida evolución en una paciente con infección por el VIH. En este caso exponemos ampliamente los síntomas, la evolución y, finalmente, la necropsia clínica. Esta enfermedad es ahora infrecuente tras la llegada de los antirretrovirales de gran actividad, no obstante, se presenta con síntomas inespecíficos y evoluciona rápidamente a la afectación multisistémica y muerte. En consecuencia, un diagnóstico precoz con base en criterios clínicos y analíticos es fundamental para instaurar el tratamiento adecuado y mejorar la supervivencia

Executive summary: Consensus document of GEHEP of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), along with SOCIDROGALCOHOL, SEPD and SOMAPA on hepatitis C virus infection management in drug users.

The micro-elimination of HCV infection in drug users (DU) in our area is a priority in order to achieve the overall elimination of this disease. Coordinated action between specialists in addiction treatment, microbiologists and physicians who treat HCV infection is required to implement infection screening, to achieve universal access to treatment and to prevent new infections and reinfections. The objective of this document was to come to a consensus on the screening, hospital referral, treatment, follow-up and prevention of HCV infection in DU by an expert panel from GEHEP/SEIMC and three scientific societies of addiction treating physicians: SEPD, SOCIDROGALCOHOL and SOMAPA

Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.This work was supported in part by grants from Fondo de Investigacion Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (http://www.ciencia.gob.es/portal/site/MICINN/menuitem.dbc68b34d11ccbd5d52ffeb801432ea0/?vgnextoid=e331aa27bfba7610VgnVCM1000001d04140aRCRD) (RD16/0025/0040), Fundacion Progreso y salud, Junta de Andalucia (https://www.sspa.juntadeandalucia.es/fundacionprogresoysalud/gestionconvocatorias/ugc/login.sol.jsp?id=10) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).Peer reviewe