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Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba-sado en INNTR.ClinicalTrials.gov, Número: NCT01829802.Método: Estudio piloto abierto, multicéntrico y aleatoriza-do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta-dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue-ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues-ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/µL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H).Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802

Background: Dual therapy has emerged as a novel concept for HIV treatment. This study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.Methods: Randomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.Results: Out of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/µL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802

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BACKGROUND: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure. Several strategies have been proposed to achieve a functional cure, some of them based on immune-mediated clearing of persistently infected cells. Here, we aimed at identifying factors related to CD8TC and CD4TC quality before cART initiation that associate with the persistence of CD8TC antiviral response after cART, inflammation levels, and the size of the viral reservoir. METHODS: Samples from 25 persons living with HIV were obtained before and after (15 months) cART initiation. Phenotype and functionality of bulk and HIV-specific T cells were assayed by flow cytometry ex vivo or after expansion in pre-cART or post-cART samples, respectively. Cell-Associated (CA) HIV DNA (total and integrated) and RNA (unspliced [US] and multiple spliced [MS]) were quantitated by real-time PCR on post-cART samples. Post-cART plasma levels of CXCL10 (IP-10), soluble CD14 (sCD14) and soluble CD163 (sCD163) were measured by ELISA. RESULTS: Pre-cART phenotype of CD8TCs and magnitude and phenotype of HIV-specific response correlated with the phenotype and functionality of CD8TCs post-cART. Moreover, the phenotype of the CD8TCs pre-cART correlated with markers of HIV persistence and inflammation post-cART. Finally, exhaustion and differentiation of CD4TCs pre-cART were associated with the composition of the HIV reservoir post-cART and the level of inflammation. CONCLUSIONS: Overall, this work provides data to help understand and identify parameters that could be used as markers in the development of immune-based functional HIV cure strategies.

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BACKGROUND: Cumulative burden of multiple mental health conditions may worsen physical health outcomes in vulnerable populations. Accordingly, identifying cumulative burdens of mental health conditions that may affect HIV treatment and care can guide public health strategies to reduce their impact on HIV-related health outcomes. This study examined the relationship between the cumulative burden of mental health conditions and factors associated with engagement in HIV care in Argentina. METHOD: Data for this study was obtained at baseline from Conexiones y Opciones Positivas en la Argentina 2 (COPA2). Participants (N = 360) were cisgender patients living with HIV who were lost to care, recruited from seven clinics serving people living with HIV in four Argentine urban centers. Cumulative burden of mental health conditions (i.e., depressive symptoms, problematic substance use, unhealthy alcohol use, and psychotic symptoms) was assessed. RESULTS: Every one-point increase in the number of mental health conditions present was associated with a decrement in patient-provider communication (b = - 0.22, p < .001), self-efficacy (b = - 0.13, p = .012), and motivation for adherence (b = - 0.11, p = .039). CONCLUSION: This study found cumulative burden of depression, problematic substance use, unhealthy alcohol use, and psychotic symptoms to be negatively associated with factors related to engagement in HIV care. Results highlight the importance of identification and treatment of challenges to mental health, in order to ameliorate their influence on engagement in HIV care.

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Objectives: To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults. Methods: In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400-900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015. Results: We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30-43) years. Baseline CD4 count was 592 (491-694) cells/mm3 and VL was 4.04 (3.5-4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (-1.2%/year versus -1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P<0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P < 0.0001) but similar rates of grade ≥2 drug-related adverse events. Conclusions: Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL.

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Since anti-HIV treatment cannot cure the infection, many strategies have been proposed to eradicate the viral reservoir, which still remains as a major challenge. The success of some of these strategies will rely on the ability of HIV-specific CD8+ T-cells (CD8TC) to clear reactivated infected cells. Here, we aimed to investigate the phenotype and function of in vitro expanded CD8TC obtained from HIV+ subjects on combination antiretroviral therapy (cART), either initiated earlier (median = 3 months postinfection, ET: Early treatment) or later (median = 20 months postinfection, DT: Delayed treatment) after infection. Peripheral blood mononuclear cells from 12 DT and 13 ET subjects were obtained and stimulated with Nef and Gag peptide pools plus IL-2 for 14 days. ELISPOT was performed pre- and post-expansion. CD8TC memory/effector phenotype, PD-1 expression, polyfunctionality (CD107a/b, IFN-γ, IL-2, CCL4 (MIP-1ß), and/or TNF-α production) and antiviral activity were evaluated post-expansion. Magnitude of ELISPOT responses increased after expansion by 103 times, in both groups. Expanded cells were highly polyfunctional, regardless of time of cART initiation. The memory/effector phenotype distribution was sharply skewed toward an effector phenotype after expansion in both groups although ET subjects showed significantly higher proportions of stem-cell and central memory CD8TCs. PD-1 expression was clustered in HIV-specific effector memory CD8TCs, subset that also showed the highest proportion of cytokine-producing cells. Moreover, PD-1 expression directly correlated with CD8TC functionality. Expanded CD8TCs from DT and ET subjects were highly capable of mediating antiviral activity, measured by two different assays. Antiviral function directly correlated with the proportion of fully differentiated effector cells (viral inhibition assay) as well as with CD8TC polyfunctionality and PD-1 expression (VITAL assay). In sum, we show that, despite being dampened in subjects on cART, the HIV-specific CD8TC response could be selectively stimulated and expanded in vitro, presenting a high proportion of cells able to carry-out multiple effector functions. Timing of cART initiation had an impact on the memory/effector differentiation phenotype, most likely reflecting how different periods of antigen persistence affected immune function. Overall, these results have important implications for the design and evaluation of strategies aimed at modulating CD8TCs to achieve the HIV functional cure.

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INTRODUCTION: Health-related quality of life (HRQoL) deterioraton is a risk factor for suicide in adults, however, this aspect has been little studied in adolescents. OBJECTIVE: To evaluate the asso ciation between HRQoL (measured with EQ-5D-5L) and suicidal risk in adolescents and its capacity for cross-sectional detection of suicidal risk. PATIENTS AND METHOD: 128 adolescents (15-19 years old) from Puerto Aysen (Chile) responded to the EQ-5D-5L questionnaire, the Okasha Suicide Scale and two anchoring questions of imminent suicide risk. A suicide risk case was considered to have a > 5 score on the Okasha scale or the affirmative answer to one of the anchoring questions. The index value of EQ-5D-5L was calculated and Odds Ratios (ORs) were estimated with confidence intervals (95% CI), adjusted for confounders. Areas under the ROC curve (AUC-ROC) were calculated to assess the discriminatory performance of EQ-5D-5L. RESULTS: 21 (16.4%) adolescents were at suicidal risk. Controlling for confounders, the EQ-5D-5L dimensions associated with suicidal risk were pain/ discomfort (OR: 2.5; 95% CI 1.1-6.1) and anxiety/depression (OR: 2.2; 95% CI 1.3-3.6). The AUC- ROC for both dimensions was 85% (95% CI 0.75-0.91) and 81% for the EQ-5D-5L index value (95% CI 0.72-0.89). CONCLUSIONS: HRQoL could be a risk factor for suicide in adolescents and in this way, the EQ-5D-5L could help in searching for high risk and hidden cases of suicidal risk.

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INTRODUCCIÓN: El deterioro de la calidad de vida relacionada con la salud (CVRS) es un factor de riesgo de suicido en adultos; no obstante, poco se ha estudiado esta dimensión en adolescentes. OBJETIVO: Evaluar la asociación entre calidad de vida relacionada con la salud, medido con el EQ-5D-5L, y riesgo suicida en adolescentes y su capacidad de detección transversal de riesgo suicida. PACIENTES Y MÉTODO: 128 jóvenes (15-19 años) de la comuna de Puerto Aysén (Chile) respondieron transversalmente el EQ-5D-5L, la escala de suicidalidad de Okasha y dos preguntas de anclaje de riesgo in minente de suicidio. Se consideró como caso de riesgo suicida a un puntaje > 5 en la escala Okasha o la respuesta afirmativa a una de las preguntas de anclaje. Se calculó el valor índice con los perfiles de salud del EQ-5D-5L. Se estimaron Odds Ratios (OR's) con intervalos de confianza (IC95%), ajustando por confusores y se calcularon áreas bajo la curva ROC (AUC-ROC) para evaluar la capacidad de pesquisa del EQ-5D-5L. RESULTADOS: 21 (16,4%) adolescentes fueron considerados como casos de riesgo suicida. Controlando por confusores, las dimensiones del EQ-5D-5L que se asociaron con riesgo suicida fueron: dolor/malestar (OR: 2,5; IC95% 1,1-6,1) y ansiedad/depresión (OR: 2,2; IC95% 1,3-3,6). El AUR-ROC para ambas dimensiones fue del 0,85% (IC95% 0,75-0,91) y de 0,81% para el valor del índice del EQ-5D-5L (IC95% 0,72-0,89). CONCLUSIONES: La CVRS podría ser un factor de riesgo de suicidio en adolescentes; y el EQ-5D-5L que mide esta dimensión, podría ayudar a pesquisar futuros casos y casos ocultos de riesgo suicida.

INTRODUCTION: Health-related quality of life (HRQoL) deterioraton is a risk factor for suicide in adults, however, this aspect has been little studied in adolescents. OBJECTIVE: To evaluate the asso ciation between HRQoL (measured with EQ-5D-5L) and suicidal risk in adolescents and its capacity for cross-sectional detection of suicidal risk. PATIENTS AND METHOD: 128 adolescents (15-19 years old) from Puerto Aysen (Chile) responded to the EQ-5D-5L questionnaire, the Okasha Suicide Scale and two anchoring questions of imminent suicide risk. A suicide risk case was considered to have a > 5 score on the Okasha scale or the affirmative answer to one of the anchoring questions. The index value of EQ-5D-5L was calculated and Odds Ratios (ORs) were estimated with confidence intervals (95% CI), adjusted for confounders. Areas under the ROC curve (AUC-ROC) were calculated to assess the discriminatory performance of EQ-5D-5L. RESULTS: 21 (16.4%) adolescents were at suicidal risk. Controlling for confounders, the EQ-5D-5L dimensions associated with suicidal risk were pain/ discomfort (OR: 2.5; 95% CI 1.1-6.1) and anxiety/depression (OR: 2.2; 95% CI 1.3-3.6). The AUC- ROC for both dimensions was 85% (95% CI 0.75-0.91) and 81% for the EQ-5D-5L index value (95% CI 0.72-0.89). CONCLUSIONS: HRQoL could be a risk factor for suicide in adolescents and in this way, the EQ-5D-5L could help in searching for high risk and hidden cases of suicidal risk.

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OBJECTIVE: We present the preliminary results of the implementation of RADAR: a community suicide prevention program in adolescents implemented in two high schools in a south region of Chile. METHOD: In a pilot study, during 2016, we implemented RADAR in two high schools of Puerto Aysen, in in the Region of Aysen of Chile. A total of 409 actors were trained (among students, school teachers, caregivers and health professionals) for the screening and referral of high suicide risk adolescents. RESULTS: Out of a total of 144 students who passed the RADAR screening systems, 29 cases were detected as suicide risk (20%) and 27 of them were opportunely referred to the Emergency Service of the Hospital of Puerto Aysen. In the second RADAR screening campaign, 3 months later, 90% of the cases no longer presented suicide risk. CONCLUSION: These results show the high proportion of ado lescents at risk of suicide who are not visible by the health system and the feasibility of implementing RADAR in the community as an effective suicide prevention intervention.

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OBJETIVO: Dar a conocer los resultados preliminares del programa comunitario RADAR (Red para la Atención y Derivación de Adolescentes en Riesgo suicida). MÉTODO: Durante el 2016, RADAR fue implementado como prueba de concepto en dos colegios de Puerto Aysén de la Región de Aysén, Chile. Se capacitó un total de 409 participantes (entre alumnos, profesores de los colegios, apoderados y profesionales de la salud) para la pesquisa y derivación de adolescentes en riego de suicidio. RESULTADOS: De un total de 144 alumnos que pasaron los sistemas de pesquisa de RADAR, se detectaron 29 casos en riesgo suicida (20%) y 27 fueron derivados oportunamente al Servicio de Urgencia del Hos pital de Puerto Aysén. En la segunda campaña de pesquisa de RADAR, 3 meses después, el 90% de los casos ya no presentaba riesgo suicida. CONCLUSIÓN: Estos resultados muestran la alta proporción de adolescentes en riesgo suicida que no son visibilizados por el sistema de salud y la factibilidad de implementar RADAR en la comunidad como una intervención preventiva efectiva.

OBJECTIVE: We present the preliminary results of the implementation of RADAR: a community suicide prevention program in adolescents implemented in two high schools in a south region of Chile. METHOD: In a pilot study, during 2016, we implemented RADAR in two high schools of Puerto Aysen, in in the Region of Aysen of Chile. A total of 409 actors were trained (among students, school teachers, caregivers and health professionals) for the screening and referral of high suicide risk adolescents. RESULTS: Out of a total of 144 students who passed the RADAR screening systems, 29 cases were detected as suicide risk (20%) and 27 of them were opportunely referred to the Emergency Service of the Hospital of Puerto Aysen. In the second RADAR screening campaign, 3 months later, 90% of the cases no longer presented suicide risk. CONCLUSION: These results show the high proportion of ado lescents at risk of suicide who are not visible by the health system and the feasibility of implementing RADAR in the community as an effective suicide prevention intervention.

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