Caracterización epidemiológica, clínica y virológica de los nuevos diagnósticos de infección por el VIH-1 (2004-2015): impacto en la respuesta al tratamiento antirretroviral

Programa Oficial de Doutoramento en Ciencias da Saúde. 5007V01[Resumen] La infección por el virus de la inmunodeficiencia humana (VIH) produce un progresivo deterioro del sistema inmunológico que conduce a la aparición de enfermedades definitorias del síndrome de inmunodeficiencia adquirida (SIDA) como consecuencia del descenso paulatino en los niveles de linfocitos T CD4+, principal diana del virus [Barré-Sinuossi et al. 1983; Popovic et al. 1983]. La introducción del tratamiento antirretroviral (TAR) de alta eficacia ha disminuido de manera significativa la morbimortalidad de los pacientes VIH+ convirtiendo a la infección por VIH en una patología crónica. La evolución de la infección en el momento actual y en países con acceso a tratamiento va a estar condicionada por diferentes factores: relacionados con el paciente (e.j. factores epidemiológicos, situación inmunológica, adherencia al tratamiento), con el virus (e.j. carga viral plasmática, presencia de mutaciones de resistencia) o con los fármacos antirretrovirales (e.j. eficacia, tolerabilidad). Por lo tanto, es importante conocer las características epidemiológicas, clínicas y virológicas en nuestra área sanitaria para establecer y optimizar las estrategias de diagnóstico y manejo clínico de los pacientes con infección por VIH. En la presente tesis se desarrollan tres estudios: - Estudio 1. Analizó las características epidemiológicas, clínicas e inmunovirológicas de los nuevos diagnósticos de infección por VIH en el área sanitaria de A Coruña durante el período 2004-2013. La principal vía de transmisión de la infección por VIH fue la sexual, con un aumento de la transmisión entre hombres que tienen sexo con hombres (HSH) en los últimos años. El diagnóstico tardío afecta a la mitad de las nuevas infecciones por VIH, y un tercio de ellas cumplen criterios definitorios de SIDA en el momento del diagnóstico; esta prevalencia ha permanecido estable durante el periodo de estudio. En cambio, la prevalencia de mutaciones de resistencia a los fármacos antirretrovirales ha disminuido significativamente (de un 10.2% a un 2.6%) en general y para cada una de las familias de fármacos antirretrovirales. - Estudio 2. Evaluó las características genéticas de las variantes de VIH circulantes en nuestra área sanitaria y comparó las características epidemiológicas, inmunovirológicas y la respuesta al TAR entre los dos subtipos genéticos más frecuentes en nuestra población, el subtipo B (65.6 %) y el subtipo F (25.8%). El subtipo F es el subtipo no-B más prevalente entre los nuevos diagnósticos de infección por VIH, a diferencia de lo observado en otras regiones de España o Europa y se transmite principalmente entre HSH. La tasa de supresión virológica fue significativamente menor en los pacientes infectados por el subtipo F del VIH en comparación con los pacientes infectados por el subtipo B (51.7% vs. 85.2%, respectivamente, a las 48 semanas de tratamiento). Se identificaron la infección por subtipo F y tener una carga viral del ARN-VIH > 100.000 copias/mL como factores predictores independientes de una peor respuesta al TAR. - Estudio 3. Evaluó la frecuencia y el impacto de la viremia plasmática de bajo nivel en la cohorte de nuevos diagnósticos de infección por VIH que habían alcanzado la supresión virológica con TAR. Aquellos pacientes con viremia persistente por debajo de los límites de cuantificación de los ensayos comerciales actualmente empleados (20 copias/mL), presentaron un mayor riesgo de fracaso virológico en el seguimiento. En resumen, los resultados obtenidos durante el desarrollo de esta tesis han permitido un conocimiento detallado de las características epidemiológicas, clínicas y virológicas de la infección por VIH en nuestra área sanitaria. Entre los principales hallazgos encontrados hay que destacar la alta tasa de diagnósticos tardíos (53.1%), la alta prevalencia del subtipo F (25.8%) y su peor respuesta al TAR en comparación con el subtipo B, y la relevancia de mantener una viremia plasmática por debajo de los límites de cuantificación y detección de los ensayos actuales (20 copias/mL) para optimizar el control de la infección en el paciente VIH+.[Resumo] A infección polo virus da inmunodeficiencia humana provoca un empeoramento progresivo do sistema inmunolóxico, que leva á aparición de enfermidades definitorias da síndrome de inmunodeficiencia adquirida (a sida) como consecuencia da lenta diminución dos niveis de linfocitos T CD4+, a principal diana do virus [Barré-Sinoussi et al. 1983; Popovic et al. 1983]. A introdución do TAR de alta eficacia diminuíu de xeito importante a morbilidade e a mortaldade dos pacientes VIH+ polo que a infección polo VIH se converteu nunha enfermidade crónica. A evolución da infección neste momento en países con acceso ao tratamento vai estar condicionada por diferentes factores ora relacionados co paciente (ex.: factores epidemiolóxicos, situación inmunolóxica, adherencia ao tratamento), ora co virus (ex.: carga viral plasmática, presenza de mutacións de resistencia) ou ora cos antirretrovirais (ex.: eficacia, tolerabilidade). Por tanto, cómpre coñecer as características epidemiolóxicas, clínicas e virolóxicas da infección polo VIH na nosa área sanitaria para establecer e optimizar as estratexias de diagnóstico e manexo clínico dos pacientes con infección polo VIH+. Nesta tese preséntanse tres estudos: - Estudo 1. Analízanse as características epidemiolóxicas, clínicas e inmuno-virolóxicas dos novos diagnósticos de infección polo VIH na área sanitaria da Coruña durante o período 2004-2013. A principal vía de transmisión da infección polo VIH foi a sexual, cun aumento da transmisión entre os homes que teñen sexo con outros homes nos últimos anos. O diagnóstico tardío abrangue a metade das novas infeccións polo VIH, e unha terceira parte delas teñen criterios definitorios de sida no momento do diagnóstico; esta prevalencia mantívose estable durante o período de estudo. Pola contra, a prevalencia das mutacións de resistencia ás drogas antirretrovirais reduciuse de xeito significativo (dende o 10.2% ao 2.6%) en xeral e para cada unha das familias de drogas antirretrovirais. - Estudo 2. Avalíanse as características xenéticas das variantes do VIH circulantes na nosa área sanitaria e compáranse as características epidemiolóxicas, inmunovirolóxicas e a resposta á terapia antirretroviral entre os dous subtipos xenéticos máis comúns na nosa poboación, o subtipo B (65.6%) e mais o subtipo F (25.8%). O subtipo F é o subtipo non-B máis prevalente entre os novos diagnósticos de infección polo VIH, a diferenza do observado noutras rexións de España ou Europa, e transmítese principalmente entre os homes que teñen sexo con outros homes. A taxa de supresión virolóxica foi significativamente menor nos enfermos infectados polo VIH e subtipo F en comparación cos pacientes con subtipo B (51.7% vs. 85.2%, respectivamente, ás 48 semanas de tratamento). Identificouse a infección polo subtipo F e unha carga viral do ARN-VIH > 100000 copias/mL como factores preditores independentes dunha peor resposta ao TAR. - Estudo 3. Avalíase a frecuencia e o impacto da viremia plasmática de baixo nivel na cohorte de persoas recentemente infectadas polo VIH que acadaran a supresión virolóxica con TAR. Aqueles pacientes con viremia persistente por baixo dos límites de cuantificación dos ensaios comerciais empregados (20 copias/mL), tiveron un maior risco de fallo virolóxico no seguimento. En resumo, os resultados obtidos durante o desenvolvemento desta tese permitiron un coñecemento preciso das características epidemiolóxicas, clínicas e virolóxicas da infección polo VIH na nosa área sanitaria. Entre os principais resultados atopados hai que salientar a alta taxa de diagnósticos tardíos (53.1%), a alta prevalencia do subtipo F (25.8%) e a súa peor resposta ao tratamento en comparación co subtipo B, e a importancia de manter a viremia plasmática por debaixo dos límites de cuantificación e detección dos ensaios actuais (20 copias/mL) para optimizar o control da infección no paciente VIH+.[Abstract] Human immunodeficiency virus (HIV) infection causes progressive deterioration of immune system leading to the presence of acquired immunodeficiency syndrome defining-diseases (AIDS) as consequence of a gradual decline of lymphocytes CD4+, main target of the virus [Barré-Sinoussi et al. 1983; Popovic et al. 1983]. High efficacy antiretroviral treatment (ART) introduction has significantly decreased the morbidity and mortality of HIV+ patients making HIV infection a chronic disease. Nowadays, the course of the infection in countries with access to treatment will be influenced by several factors: related to the patient (i.e. epidemiological factors, immunological status, adherence to treatment), to the virus (i.e. plasma viral load, presence of drug resistance mutations) or to antiretroviral therapy (i.e. efficacy, tolerability). Therefore, it is important to know epidemiological, clinical and immunovirological characteristics in our medical area to establish and optimize diagnostic strategies and the clinical management of patients with HIV infection. In this thesis, three studies have been developed: - Study 1. Epidemiological, clinical and immuno-virological characteristics of newly diagnosed HIV patients in the medical area of A Coruña during the period 2004-2013 were analysed. Main route of transmission of HIV infection was sexual route, with an increase between men who have sex with men in the last years. Late diagnosis affects half of newly-HIV infections and a third of these new infections met AIDS-defining criteria at diagnosis time; of note, these prevalences had been stable along the study period. However, the prevalence of drug resistance mutations have significantly reduced (from 10.2% to 2.6%), globally and for each of the antiretroviral-drug families. - Study 2. Epidemiological and immunovirological characteristics, as well as response to ART, between the two most common genetic subtypes in our population, subtype B (65.6%) and subtype F (25.8%) were compared. Subtype F is the most common non-B subtype between newly-HIV infections that it differs from the prevalence of this subtype observed in other Spanish or European regions. Subtype F is mainly transmitted between men who have sex with men. The rate of virological suppression was significantly lower in HIV-infected patients with subtype F compared to subtype B (51.7% vs. 85.2%, respectively, at 48 weeks of ART). Subtype F and viral load of HIV-RNA > 100.000 copies/mL were identified as independent predictor factors of a poor virological response. - Study 3. Presence and impact of low-level plasma viremia in the cohort of newly diagnosed HIV patients who had achieved virological suppression on ART were assessed. Those HIV patients with persistent viremia below limits of quantification (20 copies/mL) are associated with an increased risk for virological failure during follow-up. In summary, the results obtained during the developing of this thesis have allowed a detailed knowledge of epidemiological, clinical and immunovirological characteristics of HIV infection in our medical area. Among the major findings should be noted the high rate of late diagnosis (53.1%), high prevalence of subtype F (25.8%) and their worse response to treatment compared to subtype B, and the relevance of maintain plasma viremia below the limits of quantification and detection of current test (20 copies/mL) to optimize the control of infection in HIV-infected patients

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years

[Abstract] To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; PI13/0226

Late HIV Diagnosis but Earlier Antiretroviral Treatment Initiation in Northwest Spain: Impact of Current Treatment Guidelines

[Abstract] Background: Current HIV treatment guidelines recommend antiretroviral treatment (ART) initiation for all HIV-infected individuals regardless of CD4 count. This study evaluates the immunological and virological status and the clinical characteristics of patients who have started ART in the last 8 years in the Northwest of Spain. Methods: All HIV-infected patients who have started ART between January 2009 and December 2016 at a reference hospital in the Northwest of Spain were included in this retrospective observational study. Epidemiological, clinical, and immunovirological features and antiretroviral drugs used for initiation were recorded. A statistical analysis was performed using SPSS version 19 software. Categorical and continuous variables were compared by the specific statistical tests, and a logistic regression model was used to identify time associated with Center for Disease Control and Prevention (CDC) categories change. Results: A high proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm3 in the last 8 years. From these, most of them (68.3%) had <350 CD4 counts at first contact with HIV specialist medical team, 12.2% had no indications for ART initiation in the last clinic visit before ART initiation according to the national guidelines at that moment, 11.0% were lost to follow-up because of lack of compliance with scheduled visits and 8.5% of patients refused treatment. A logistic regression model showed that a delay of one month since the first contact with HIV specialist medical team to ART initiation involves a risk of worsening in the CDC clinical category (odds ratio: 1.02 [95% confidence interval: 1.012-1.029]; P < .001). A trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. Conclusion: High proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm3 in the last 8 years. The main reasons for this problem were analyzed and an important rate of late diagnosis was identified. However, a trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. These findings highlight the need to promote and facilitate HIV testing to reduce the late diagnosis as well as counseling on HIV prevention, treatment, and linkage care

Caracterización epidemiológica, clínica y virológica de los nuevos diagnósticos de infección por VHC en Galicia (2014-2015)

Abstrac

Characterization of chronic HCV infection in Northwest Spain: impact of the treatment strategic plan of the Spanish National Health Service on HCV cure

[Abstract] The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; FI14/0055

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

[Abstract] Objectives. The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA <50 copies/mL) on ART. Methods. Newly diagnosed (2004–13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan–Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. Results. A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524–11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA 200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728–66.261), P = 0.092]. Conclusions. Blips are frequent (22.7%) among HIV-infected patients with sustained virological suppression on ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL).Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/0226

Clinical experience with the integrase inhibitors Dolutegravir and Elvitegravir in HIV-infected patients: efficacy, safety and tolerance

[Abstract] Two integrase inhibitors (INSTIs), dolutegravir (DTG) and elvitegravir/cobicistat (EVG/COBI), have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in north-western Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. A total of 542 DTG (n = 275)- or EVG/COBI (n = 267)-based therapies were initiated during the study period. Overall, more than 90% of naïve and pre-treated patients had virological suppression in both groups after 48 weeks of initiation of treatment per-protocol snapshot analysis. During follow-up, 10.2% of patients were treated with DTG and 4.5% of those treated with EVG discontinued due to adverse events (AE). In the case of DTG mainly related to neuropsychiatric disturbances (70.4%) and for EVG/COBI with gastrointestinal discomfort (50%). Female sex [HR 2.255 (95%CI 1.121–4.535), p = 0.023] and DTG treatment [HR 2.453 (95%CI 1.221–4.931), p = 0.012] were associated with AE discontinuations. Specifically for neuropsychiatric events, DTG treatment [HR 5.906 (95%CI 1.954–17.846), p = 0.002] and receiving abacavir/lamivudine/DTG [HR 4.380 (95%CI 1.348–14.233), p = 0.014] were identified as predictive risk factors for treatment discontinuations in two different multivariate analyses. A high percentage of AE discontinuations not previously described in clinical trials has been observed, especially with DTG. Female gender and DTG treatment were identified as risk factors for AE discontinuation. DTG-based therapies, especially in combination with abacavir/lamivudine, were associated with an increased risk of treatment discontinuation due to neuropsychiatric AE.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; PI16/0215

Efectividad y seguridad de daclatasvir/ sofosbuvir con o sin ribavirina en pacientes infectados por el genotipo 3 del virus de la hepatitis C: resultados en práctica clínica real

[Abstract] OBJECTIVE: Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice. METHODS: An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. RESULTS: A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. CONCLUSIONS: Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.[Resumen] OBJETIVOS: Los antivirales de acción directa han demostrado una alta eficacia en todos los genotipos del virus de la hepatitis C (VHC), pero los tratamientos para el genotipo 3 (G3) siguen siendo un desafío, principalmente en pacientes cirróticos. El objetivo de este estudio es analizar la efectividad y la seguridad del daclatasvir asociado con sofosbuvir con o sin ribavirina en pacientes infectados por G3-VHC en la práctica clínica real. PACIENTES Y MÉTODOS: Estudio observacional, prospectivo, de cohorte de más de 2,5 años, en pacientes adultos infectados con G3-VHC, en todos los estadios de fibrosis, incluidos los pacientes con cirrosis descompensada. El tratamiento fue una combinación de sofosbuvir 400 mg / día + daclatasvir 60 mg / día, con o sin una dosis de ribavirina ajustada por peso durante 12 o 24 semanas. El criterio de valoración principal de eficacia fue la tasa de respuesta virológica sostenida 12 semanas después del tratamiento (RVS12). La variable principal de seguridad fue la tasa de suspensiones de tratamiento secundaria a eventos adversos graves. RESULTADOS: Se incluyeron 111 pacientes, 32.4% cirróticos y 29.9% con experiencia previa de tratamiento antiviral. La tasa global de RVS12 fue del 94,6%, mientras que la tasa de RVS12 en pacientes con estadio de fibrosis F3-4 fue del 90,8% frente al 100% en pacientes con fibrosis F0-2 (p = 0,03). En pacientes cirróticos, la RVS12 fue del 100% en comparación con el 40%, dependiendo de si se agregó o no ribavirina a daclatasvir / sofosbuvir (p = 0,001). Ninguna otra variable basal del paciente o del tratamiento influyó en la efectividad del tratamiento. No se observó ninguna suspensión del tratamiento secundario a eventos adversos graves. CONCLUSIONES: Daclatasvir / sofosbuvir ± ribavirina es altamente efectivo en pacientes infectados por G3-VHC. Los grados avanzados de fibrosis disminuyen significativamente la efectividad de este tratamiento, lo que motiva la necesidad de la adición de ribavirina en pacientes cirróticos. El régimen fue seguro y bien tolerado

Molecular characterization of HIV-1 infection in Northwest Spain (2009–2013): investigation of the subtype F outbreak

[Abstract] Background. HIV-1 subtype B is the predominant one in European regions several, while other subtypes and recombinants are also circulating with high prevalence. A sub-epidemic of subtype F with specific characteristics and low response to treatment has been recently identified in Galicia. In this study we investigated the characteristics of the HIV-1 subtype F sub-epidemic in A Coruña and Santiago de Compostela in Northwest Spain. Methods. 420 newly HIV-1 diagnosed patients during 2009–2013 were enrolled in this study. HIV-1 subtyping was carried out using automated subtyping tools and phylogenetic analysis. Molecular epidemiology investigation of subtypes B and F was performed by means of phylogenetic analysis using fast maximum likelihood. Phylodynamic analysis was performed using Bayesian method as implemented in BEAST v1.8. Results. Subtype B found to be the predominant (61.2% and 70.4%) followed by subtype F (25.6% and 12.0%) in both areas (A Coruña and Santiago de Compostela, respectively). The latter found to mainly spread among men having sex with men (MSM). The vast majority of subtype F lineages from both areas clustered monophyletically, while subtype B sequences clustered in several tree branches. The exponential growth of subtype F sub-epidemic dated back in 2008 by means of phylodynamic analysis. Most of new infections during 2009–2013 occurred within the subtype F transmission cluster. Conclusions. Subtype F circulates at high prevalence in A Coruña and Santiago de Compostela in Northwest Spain, suggesting that the HIV-1 epidemic in this region has distinct characteristics to the rest of Spain. Subtype F has being spreading among MSM and is currently the most actively spreading network. The single cluster spread of this local sub-epidemic might provide an explanation for the distinct characteristics and the low response to antiretroviral treatment

Teleconsultation for the pharmaceutical care of HIV outpatients in receipt of home antiretrovirals delivery: clinical, economic, and patient-perceived quality analysis

Observational study[Abstract] Background/Introduction: Pharmacist teleconsultations, combined with home drug delivery or mail-order pharmacy (MOP), can help hospital outpatients with difficulties accessing treatment. The objectives of this study are to describe a teleconsultation protocol and to evaluate clinical, economic, and patient-perceived quality results. Materials and Methods: A cohort observational study was carried out for 3 years on HIV outpatients. Clinical variables were adherence, plasma HIV-RNA, and CD4+ levels. A pharmacoeconomic analysis was carried out through a cost-minimization study. Patient-perceived quality was assessed through a satisfaction survey. Simple random sampling was performed for 95% safety, accuracy ±1%, and losses ±20%. Results: The 38 participants (sample size) consisted of 82% male patients, aged 44.7 ± 8.4 years. There were 854 teleconsultations and 100% treatment adherence. All HIV outpatients kept virally suppressed (p = 1.00) and maintained a controlled immunological level (p = 0.87). The economic evaluation revealed 137 ± 23 € patient/year costs-saved and 18.5 ± 7.2 h/patient/year working time gained. Patient-perceived quality average score was >9.4 out of 10 in all items; the most valued factors were the saving of direct costs and reconciliation with work commitments (45%) and the least valued attributes were making the payment for the shipment and having to adjust to a telephone appointment (41%). Discussion/Conclusions: A teleconsultation protocol associated with home antiretrovirals delivery or MOP obtains a high degree of satisfaction from the HIV hospital outpatients receiving treatment, without repercussions on the therapeutic objectives and with the saving of important direct costs for the patient and indirect costs in relation to labor productivity