Cardiovascular efficacy and safety of bococizumab in high-risk patients

BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin– kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of −56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.

Adherence to and effectiveness of Highly Active Antiretroviral Treatment for HIV infection: assessing the bidirectional relationship

It is well-established that high adherence to HAART is a major determinant of virological and immunological success. Furthermore, psycho-social research has identified a wide range of adherence factors. Our objective was to assess the bi-directional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCOCOPILOTE study. An econometric approach was implemented through a bivariate twoequation simultaneous system, studying the factors associated with both adherence and undetectability of HIV plasma viral load. Our results highlight that good biological results induced by adherence reinforce continued adherence. This strengthens the argument that patients who do not experience rapid improvements in their immunological and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, it rules out the hypothesis that HAART leads to "false reassurance" among HIV infected patients.Adherence ; HIV ; relationship between adherence and effectiveness ; simultaneous equations ; GEE

Adherence as a Predictor of Sexual Behaviors in People Living with HIV/AIDS during the First Year of Antiretroviral Therapy in Rural Cameroon: Data from Stratall ANRS 12110/ESTHER Trial

Objective: This study aims to investigate the time pattern of inconsistence condom use (ICU) during the first year of antiretroviral therapy (ART) and its relationship with treatment adherence in naive HIV-infected adult patients. ' Methods: Data collection was nested within a longitudinal trial on HIV treatment. ICU was defined as reporting to have "never", "sometimes" or "nearly always" used condoms with one's main or casual partner(s) - either HIV-negative or of unknown HIV status in the three previous months. Adherence was defined as taking 100% of their ART prescribed doses in the 4 days before the visit and "not having interrupted treatment", even once, for more than two consecutive days during the 4 previous weeks. Mixed logistic regression was used to study the relationship between adherence and ICU. Results: Among the 459 patients enrolled, 212 (46%) during 334 visits reported to have had sexual intercourse at least once with their partner(s) - either HIV-negative or of unknown HIV status-during the first 12 months of ART. The proportion of ICU was 76%, 50% and 59% at month 0 (M0), month 6 (M6) and month 12 (M12), while 60% and 66% of patients were ART-adherent at M6 and M12, respectively. After adjustment for the frequency of sexual activity, type of sexual partner(s), perceived social class and desire for a child, patients adherent to ART were less likely to report ICU when compared with baseline (AOR [95% CI]: 0.38 [0.19-0.76]; P = 0.006). Conclusions: Adherence to ART is associated with a lower risk of ICU but this result needs to be interpreted carefully. As adherence behaviors are not only determined by problems with the healthcare systems but also by social barriers encountered by patients in their daily life, counseling should not only be ART adherence-centered but also patient-centered, including sexual risk minimization and psychosocial support

Discrimination against HIV-Infected People and the Spread of HIV: Some Evidence from France

BACKGROUND: Many people living with HIV/AIDS (PLWHA) suffer from stigma and discrimination. There is an ongoing debate, however, about whether stigma, fear and discrimination actually fuel the persisting spread of HIV, or slow it down by reducing contacts between the whole population and high-risk minorities. To contribute to this debate, we analysed the relationship between perceived discrimination and unsafe sex in a large sample of French PLWHAs. METHODOLOGY/PRINCIPAL FINDINGS: In 2003, we conducted a national cross-sectional survey among a random sample of HIV-infected patients. The analysis was restricted to sexually active respondents (N = 2,136). Unsafe sex was defined as sexual intercourse without a condom with a seronegative/unknown serostatus partner during the prior 12 months. Separate analyses were performed for each transmission group (injecting drug use (IDU), homosexual contact, heterosexual contact). Overall, 24% of respondents reported experiences of discrimination in their close social environment (relatives, friends and colleagues) and 18% reported unsafe sex during the previous 12 months. Both prevalences were higher in the IDU group (32% for perceived discrimination, 23% for unsafe sex). In multivariate analyses, experience of discrimination in the close social environment was associated with an increase in unsafe sex for both PLWHAs infected through IDU and heterosexual contact (OR = 1.65 and 1.80 respectively). CONCLUSIONS: Our study clearly confirms a relationship between discrimination and unsafe sex among PLWHAs infected through either IDU or heterosexual contact. This relationship was especially strong in the heterosexual group that has become the main vector of HIV transmission in France, and who is the more likely of sexual mixing with the general population. These results seriously question the hypothesis that HIV-stigma has no effect or could even reduce the infection spread of HIV

Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia

BACKGROUND: The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV) drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. METHODS: The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0) and third month (M3) follow up visits. RESULTS: A total of 400 and 383 patients at baseline (M0) and at follow up visit (M3) respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food) was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21). Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81). However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55) and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51) were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. CONCLUSION: The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot reliably be predicted by a few patient characteristics that are assumed to vary with time. Adherence is a process, not a single event, and adherence support should be integrated into regular clinical follow up

Les enjeux économiques et sociaux de l’infection par le VIH à l’ère des multithérapies antirétrovirales

Cet article présente une synthèse des principaux aspects traités par la littérature internationale de sciences humaines et sociales (SHS) depuis l’apparition des multithérapies antirétrovirales en 1996. Initialement sollicitées pour contribuer à l’observance de ces traitements, les SHS ont permis de dépasser l’approche «prédictive», jusque là dominante dans les disciplines biomédicales, qui visait à identifier sur la base d’un nombre limité de caractéristiques a priori les patients censés présenter un «haut risque» de non-observance. Elles ont montré que l’observance est un processus d’apprentissage dynamique qui dépend avant tout de l’expérience subjective vécue par les patients. La «chronicisation » de la maladie VIH a conduit les SHS à s’intéresser à l’impact des traitements sur tous les aspects de la vie quotidienne (de l’insertion professionnelle à la sexualité), en même temps qu’elles soulignent la contradiction entre les espoirs suscités par des multithérapies économiquement coût-efficaces d’une part, et la précarité sociale d’une proportion croissante de personnes atteintes, d’autre part. Ces recherches débouchent sur des recommandations visant à adapter les politiques publiques de lutte contre l’épidémie de sida tout en préservant le potentiel d’innovations qu’elles ont favorisé dans les systèmes de santé et de protection sociale, ainsi que dans les relations médecin/malade

Les enjeux économiques et sociaux de l’infection par le VIH à l’ère des multithérapies antirétrovirales : Apports des sciences humaines et sociales

Cet article présente une synthèse des principaux aspects traités par la littérature internationale de sciences humaines et sociales (SHS) depuis l’apparition des multithérapies antirétrovirales en 1996. Initialement sollicitées pour contribuer à l’observance de ces traitements, les SHS ont permis de dépasser l’approche «prédictive», jusque là dominante dans les disciplines biomédicales, qui visait à identifier sur la base d’un nombre limité de caractéristiques a priori les patients censés présenter un «haut risque» de non-observance. Elles ont montré que l’observance est un processus d’apprentissage dynamique qui dépend avant tout de l’expérience subjective vécue par les patients. La «chronicisation» de la maladie VIH a conduit les SHS à s’intéresser à l’impact des traitements sur tous les aspects de la vie quotidienne (de l’insertion professionnelle à la sexualité), en même temps qu’elles soulignent la contradiction entre les espoirs suscités par des multithérapies économiquement coût-efficaces d’une part, et la précarité sociale d’une proportion croissante de personnes atteintes, d’autre part. Ces recherches débouchent sur des recommandations visant à adapter les politiques publiques de lutte contre l’épidémie de sida tout en préservant le potentiel d’innovations qu’elles ont favorisé dans les systèmes de santé et de protection sociale, ainsi que dans les relations médecin/malade.This article presents a synthesis of the main topics covered by social science research (SSR) on HIV/AIDS, since the advent of highly active antiretroviral therapies (HAART) in 1996. SSR has shown that non-adherence cannot be reliably «predicted» on the sole basis of a few a priori patient characteristics that clinicians could easily identify before initiation of HAART, and that a dynamic approach to adherence, continuously monitoring the impact of patients’ subjective experience with HAART is needed. In relationship with the evolution of HIV infection toward a «chronic disease», SSR has dealt with the impact of HAART on all aspects of patients’ daily lives (from employment and professional status to sexuality). It has also emphasised the potential contradictions between the hopes generated by these cost-effective therapeutic advances, on the one hand, and the high social vulnerability of a growing proportion of people living with HIV-AIDS, on the other hand. Finally, SSR suggests recommendations for «normalising» AIDS public policies without losing the potential for innovations that the fight against this epidemic has introduced in health care and «Social Security» systems, as well as physician-patient’s relationships

Cardiovascular efficacy and safety of bococizumab in high-risk patients

Background: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. Methods: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. Results: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). Conclusions: In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .)

LES CONSÉQUENCES DU CANCER SUR LA VIE SOCIALE ET PROFESSIONNELLE

International audienceL’objectif de cette étude consiste à repérer les facteurs associés au vécu de situationsde discrimination et à repérer ceux qui apparaissent plus spécifiquement dans un environnementamical, familial ou de travail. L’expérience subjective d’attitudes de rejet ou de discrimination dansl’environnement familial, amical ou social concerne 9,1 % des personnes atteintes de cancer– une enquête sur les conditions de vie des personnes séropositives montre que 33%des personnes infectées par le virus de l’immunodéficience humaine (VIH) se disent victimesde discriminations. Un jeune âge, la précarité financière, des séquelles des traitements gênantes,un traitement lourd associant chimiothérapie, chirurgie et radiothérapie, le contact avecune association de malades ainsi que la consommation de médicaments psychoactifs augmententla probabilité de déclarer avoir fait l’objet de rejet ou de discrimination. Ces résultats soulignentà la fois le rôle de la précarité sociale, mais aussi des spécificités de la prise en charge médicaledes cancers ainsi que leurs effets psychosociaux