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Background: Unlike their younger counterparts, some of today's older HIV patients were diagnosed before the advent of highly active antiretroviral therapy (HAART). The psychosocial and behavioral outcomes of people living with HIV (PLWH) have been widely studied, and associated factors are well known. However, their evolution both in terms of age and diagnosis-specific cohort effects is not well understood., Methods: Data from the ANRS-VESPA2 cross-sectional survey, representative of French PLWH, were used to investigate whether psychosocial and behavioral outcomes such as quality of life, need for support and HIV status disclosure, evolve under both the influence of patients' age and diagnosis-specific cohort effects. A semi-parametric generalized additive model (GAM) was employed. The physical and mental components of health-related quality of life, the need for material and moral support, and HIV-status disclosure, constituted our outcomes., Results: Non-linear diagnosis-specific cohort effects were found for physical and mental QoL and HIV-status disclosure. Overall, physical QoL was better in recently diagnosed patients than in those diagnosed in the early 1980s. An increasing influence of diagnosis-specific cohort effects between 1983 and 1995 was observed. No cohort effects were noticeable between 1996 and 2000, while an increasing influence was apparent for patients diagnosed with HIV from 2000 to 2011 (year of study). For mental QoL, the only increase was observed in participants diagnosed with HIV between 1983 and 2000. The relationship between diagnosis-specific cohort effects and HIV status disclosure was negative overall: participants diagnosed after 2000 were much less likely to disclose than those diagnosed before 1995. The effect of age was significantly associated with all outcomes, with a non-linear influence on mental QoL and with the need for material/moral support., Conclusions: Psychosocial and behavioral outcomes are complex processes which can be explained in different ways by a combination of the clinical and social contexts which PLWH are exposed to at the time of diagnosis, and by developmental characteristics. A greater understanding of these processes could inform healthcare policy-making for specific HIV generations and different HIV age groups.

Background: There are few data comparing patient-reported outcomes (PROs) in randomized trials of initial antiretroviral therapy. We present results from a substudy of the NEAT001/ANRS143 trial., Methods: The randomized trial compared first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus TDF/FTC 245/200 mg once daily. Changes in PROs were assessed with 3 questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major depressive disorder (MDD) was defined as CES-D ≥ 16. General estimating equations were used to model change over 96 weeks in PROs from baseline., Results: Of the 805 participants, 797 (99%) contributed to the substudy. Baseline PRO data were similar for the 2 randomized groups. Health status improved over time with a mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95% confidence interval (CI): 6.5 to 9.4; P < 0.001], and no statistically significant differences between groups (difference of 0.3 on VAS score (95% CI: -1.7 to 2.3); P = 0.7, global P value ≥0.05 for all domains over follow-up). There was no significant difference between groups on CES-D [difference of -0.1 (95% CI: -1.3 to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of convenience (P = 0.03) and fitted less well into patients' lifestyle (P = 0.007) than the TDF/FTC + DRV/r regimen, and was associated with lower treatment satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)]., Conclusion: PROs improved after starting antiretroviral therapy, with no statistically significant difference between groups. The lower satisfaction with RAL + DRV/r may be explained by twice-daily administration.

Introduction: Decreasing international financial resources for HIV and increasing numbers of antiretroviral treatment (ART)-treated patients may jeopardise treatment continuity in low-income settings. Using data from the EVOLCam ANRS-12288 survey, this study aimed to document the prevalence of unplanned treatment interruption for more than 2 consecutive days (TI>2d) and investigate the associated individual and health care supply-related factors within the Cameroonian ART programme., Methods: A cross-sectional mixed methods survey was carried out between April and December 2014 in 19 HIV services of the Centre and Littoral regions. A multilevel logistic model was estimated on 1885 ART-treated patients in these services to investigate factors of TI>2d in the past 4 weeks., Results: Among the study population, 403 (21%) patients reported TI>2d. Patients followed up in hospitals reporting ART stock-outs were more likely to report TI>2d while those followed up in the Littoral region, in medium- or small-sized hospitals and in HIV services proposing financial support were at lower risk of TI>2d. The following individual factors were also associated with a lower risk of TI>2d: living in a couple, having children, satisfaction with attention provided by doctor, tuberculosis co-infection and not having consulted a traditional healer., Conclusions: Besides identifying individual factors of TI>2d, our study highlighted the role of health care supply-related factors in shaping TI in Cameroon's ART programme, especially the deleterious effect of ART stock-outs. Our results also suggest that the high proportion of patients reporting TI could jeopardise progress in the fight against HIV in the country, unless effective measures are quickly implemented like ensuring the continuity of ART supply., (© 2018 John Wiley & Sons Ltd.)

The effectiveness of antiretroviral therapy (ART) depends on optimal clinical management and patient adherence. Little is known about patient characteristics that clinicians consider in the management of ART adherence. Exploring this issue, five focus groups were conducted with 31 HIV-clinicians from across France. A qualitative typological analysis suggests that clinician management of patient adherence is based on characteristics that coalesce into seven patient profiles. For the "passive" patient, described as taking ART exactly as prescribed without questioning their doctor's expertise, a directive and simple management style was preferred. The "misleading" patient is characterized as concerned with social desirability and as reporting no adherence difficulties for fear of displeasing their doctor. If clinical outcomes are suboptimal, the clinicians' strategy is to remind them of the importance of open patient-clinician communication. The "stoic" patient is described as requesting and adequately taking the most potent ART available. Here, clinicians emphasize assessment of side effects, which the patient may minimize. The "hedonistic" patient's festive lifestyle and sexual risk-taking are seen as compromising adherence; with them, clinicians stress the patient's responsibility for their own health and that of their sexual partners. The "obsessive" patient is portrayed as having an irrational fear of ART failure and an inability to distinguish illusory from genuine adherence barriers. With this patient, clinicians seek to identify the latter. The "overburdened" patient is recognized as coping with life priorities that interfere with adherence and, with them, a forgiving ART is favored. The "underprivileged" patient is presented as having limited education, income and housing. In this case, clinicians seek to improve the patient's living conditions and access to care. These results shed light on HIV clinicians' ART adherence management. The value of these profiles for HIV care and patients should be investigated.

The effect of early adherence on long-term viral suppression was assessed among 1281 patients with HIV starting a protease inhibitor-containing regimen in 1997-1999, followed up to 12 years. Association between 4-month adherence (3-level score) and prolonged viral suppression was evaluated using a multivariate mixed logistic model in 891 eligible patients. High 4-months adherence [odds ratio (95% confidence interval): 3.72 (1.98 to 6.98)] was associated with long-term prolonged viral suppression, irrespective of maintenance adherence. This unexpected long-term virological impact of early adherence reinforces the message that, when starting antiretrovirals, all means should be mobilized to ensure optimum early adherence to achieve prolonged antiretroviral success.

Objectives: We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART)., Patients and Methods: In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART., Results: Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm 3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes., Conclusions: In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm(3)) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm(3)) and other eligibility criteria: ≤100; 100-200; 200-350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2-71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1-98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts., Competing Interests: statement C.I. has received honoraria for services rendered to Gilead Sciences. All other authors declare no competing interests.

Background: Although the role of clinical/biological factors associated with mortality has already been explored in HIV-infected patients on antiretroviral therapy (ART), to date little attention has been given to the potential role of social vulnerability. This study aimed to construct an appropriate measure of social vulnerability and to evaluate whether this measure is predictive of increased mortality risk in ART-treated patients followed up in the ANRS CO8 APROCO-COPILOTE cohort., Methods: The cohort enrolled 1,281 patients initiating a protease inhibitor-based regimen in 1997-1999. Clinical/laboratory data were collected every 4 months. Self-administered questionnaires collected psycho-social/behavioural characteristics at enrolment (month [M] 0), M4 and every 8-12 months thereafter. A multiple correspondence analysis using education, employment and housing indicators helped construct a composite indicator measuring social vulnerability. The outcome studied was all-cause deaths occurring after M4. The relationship between social vulnerability and mortality, after adjustment for other predictors, was studied using a shared-frailty Cox model, taking into account informative study dropout., Results: Over a median (IQR) follow-up of 7.9 (3.0-11.2) years, 121 deaths occurred among 1,057 eligible patients, corresponding to a mortality rate (95% CI) of 1.64 (1.37, 1.96)/100 person-years. Leading causes of death were non-AIDS defining cancers (n=26), AIDS (n=23) and cardiovascular diseases (n=12). Social vulnerability (HR [95% CI] =1.2 [1.0, 1.5]) was associated with increased mortality risk, after adjustment for other known behavioural and bio-medical predictors., Conclusions: Social vulnerability remains a major mortality predictor in ART-treated patients. A real need exists for innovative interventions targeting individuals cumulating several sources of social vulnerability, to ensure that social inequalities do not continue to lead to higher mortality.

Objectives: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon., Methods: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively., Results: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]., Conclusions: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa., (© 2014 British HIV Association.)

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm3 for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories:HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts' considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled "Weighing the merits of early ART in the face of uncertainties was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France.

Background: The additional burden of HCV infection in HIV-HCV-coinfected individuals may have some consequences on adherence to HAART. Few studies have explored the pattern of correlates of non-adherence to HAART while simultaneously considering the impact of HCV treatment and depressive symptoms on adherence to HAART. We used longitudinal data to assess factors associated with non-adherence to HAART., Methods: The French national prospective cohort ANRS-CO13-HEPAVIH is a multicentrer cohort, which recruited 1,175 HIV-HCV-coinfected patients in 17 hospital outpatient units delivering HIV and HCV care in France between October 2006 and June 2008. For this analysis, we selected participants on HAART with self-reported data for adherence to HAART (n=727 patients, 1,190 visits). Data were collected using self-administered questionnaires and medical records. A mixed logistic regression model based on an exchangeable correlation matrix was used to identify factors associated with non-adherence to HAART., Results: Patients reported non-adherence to HAART in 808 (68%) of the 1,190 visits. Four variables remained associated with non-adherence to HAART after multivariate analysis: hazardous alcohol consumption, cocaine use and depressive symptoms, regardless of whether treatment for depression was being received. Finally, patients being treated for HCV infection were less likely to be non-adherent to HAART., Conclusions: Besides the problem of polydrug use, two other dimensions deserve special attention when considering adherence to HAART in HIV-HCV-coinfected patients. Access to HCV treatment should be encouraged as well adequate treatment for depression in this population to improve adherence and response to HAART., Competing Interests: statement The authors have no conflict of interest to declare.

Background: In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial., Methods: The randomised, controlled, non-inferiority Stratall trial was done in a decentralised setting in Cameroon. Between May 23, 2006, and Jan 31, 2008, ART-naive adults were randomly assigned (1:1) to clinical monitoring (CLIN) or viral load and CD4 cell count plus clinical monitoring (LAB) and followed up for 24 months. We calculated costs, number of life-years saved (LYS), and incremental cost-effectiveness ratios (ICERs) with data from patients who had been followed up for at least 6 months. We considered two cost scenarios in which viral load plus CD4 cell count tests cost either US$95 (scenario 1; Abbott RealTime HIV-1 assay) or $63 (scenario 2; generic assay). We compared ICERs with a WHO-recommended threshold of three times the per-person gross domestic product (GDP) for Cameroon ($3670-3800) and an alternative lower threshold of $2385 to determine cost-effectiveness. We assessed uncertainty with one-way sensitivity analyses and cost-effectiveness acceptability curves., Findings: 188 participants who underwent LAB and 197 who underwent CLIN were followed up for at least 6 months. In scenario 1, LAB increased costs by a mean of $489 (SD 430) per patient and saved 0·103 life-years compared with CLIN (ICER of $4768 [95% CI 3926-5613] per LYS). In scenario 2, the incremental mean cost of LAB was $343 (SD 425) -ie, an ICER of $3339 (2507-4173) per LYS. A combined strategy in which LAB would only be used in patients starting ART with a CD4 count of 200 cells per μL or fewer suggests that 0·120 life-years would be saved at an additional cost of $259 per patient in scenario 1 (ICER of $2167 [95% CI 1314-3020] per LYS) and $181 in scenario 2 (ICER of $1510 [692-2329] per LYS) when compared with CLIN., Interpretation: Laboratory monitoring was not cost effective in 2006-10 compared with clinical monitoring when the Abbott RealTime HIV-1 assay was used according to the $3670 cost-effectiveness threshold (three times per-person GDP in Cameroon), but it might be cost effective if a generic in-house assay is used., Funding: French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Antiretroviral therapy for the treatment of HIV infection requires high levels of adherence to both maintain plasma HIV RNA at undetectable levels and prevent the emergence of drug resistance. As adherence to treatment is a major criterion for the evaluation of therapeutic outcomes, randomized clinical trials (RCTs) conducted among HIV-infected patients commonly include an assessment of adherence. However, there is still no gold-standard tool for assessing adherence behaviors in HIV RCTs. The methods currently used to collect and analyze adherence data are varied, which makes the comparison of results between studies difficult. The scope of this article is to review and discuss the range of adherence measures currently used in RCTs conducted among HIV-infected adults.

Background: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes., Methods: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations., Results: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly., Conclusions: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

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 naïve 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.

The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.

Purpose of Review: Given the lack of evidence on how to best design and implement antiretroviral therapy (ART) scaling-up policies, operational research has seen a surge in interest. There is, however, little published information on the contribution of operational research in ART programs' implementation or in improvement of associated outcomes. The article focuses therefore on how operational research may contribute to such improvements and what the key enabling factors are for its integration into program frameworks., Recent Findings: One of the most systematic operational research linked to a national ART program on the African continent was conducted in Cameroon between 2006 and 2010. Along with operational research carried out elsewhere in Africa, it helped demonstrate that a strategy of decentralizing HIV care can increase treatment coverage and improve early access to care, while maintaining good clinical outcomes. Multipartnership between local researchers, national authorities, healthcare professionals and the civil society is the key enabling factor for the relevance of operational research and the translation of its results into policy and practice., Summary: In spite of a dramatic increase in access to ART during recent years in low-income countries, the fight against HIV remains a failure in terms of the goal of breaking the pandemic dynamic. Operational research is needed more than ever to face this challenge.

Objectives: The aim of this study was to identify factors associated with non-adherence over a 10 year follow-up of the APROCO-COPILOTE cohort during the maintenance phase of highly active antiretroviral therapy (HAART)., Methods: Overall, 1010 patients participated in this analysis, each having had at least 12 months of follow-up after HAART initiation and at least one self-reported adherence measure available during the follow-up period (month 12-month 120). Data collection was based on clinical records and self-administered questionnaires that gathered patients' psychosocial characteristics and experience with HIV disease and treatment. First, a generalized estimating equations (GEE) model was used to identify non-adherence predictors. Secondly, a Heckman two-stage approach was used in order to account for missing data bias and to measure the extent to which this could affect the results of the first model., Results: Non-adherent behaviour was reported by 747 patients (2070 visits). After correcting for the bias due to missing data, non-adherence was independently associated with side effects, having a three times or more daily dosing regimen, experience of being at clinical stage B/C and being diagnosed as HIV-positive for <6 months. Non-adherence was more likely among patients who were younger, had children, were born in the European Union, had depressive symptoms, consumed alcohol daily and declared a lack of support from their main partner. Adjusting for missing outcome data changed the pattern of predictors., Conclusions: Reasons for non-adherence depended on both psychosocial conditions and treatment-related characteristics. To improve long-term patient outcomes for those at risk of adherence failure, tailor-made patient-specific psychosocial interventions and regimen-based strategies with improved tolerance need to be implemented.

Even in the highly active antiretroviral therapy (HAART) era, individuals HIV-infected through injecting drug use (IDUs) are at increased risk of death due to the burden of competing events such as liver disease, overdose and suicide. The objective of this study was to explore the role which life events' experience, in particular drug-related events such as detoxification or withdrawal symptoms, may play on the risk of death in HIV-infected IDUs. Our analysis was based on longitudinal data of 296 HIV-infected IDUs from when they started HAART. Data collection included medical records and patient's self-reports detailing, among other information, life events including drug-related problems. Multiple imputations for missing data in the explanatory variables together with Cox models were used to identify predictors of death. During HAART follow-up, 26 deaths occurred, corresponding to 1.8 deaths per 100 person-years. The majority (N=8) were attributable to liver disease while 5 were from unknown causes (found deceased at home or in a car). After adjustment for age and time-dependent viral load (>10,000 cp/ml) individuals experiencing withdrawal symptoms had a fivefold increased risk of death with respect to the others. Withdrawal symptoms in IDUs living with HIV reflect physicians' difficulties in managing their patients' opioid dependence. Early detection and increasing substitution dosages or switching to a more adequate treatment could prevent possible drug-related deaths.

Aims: To date, no data exist assessing the impact of either methadone or buprenorphine on adherence to highly active antiretroviral therapy (HAART) in the long term. This study was conducted in order to evaluate whether receiving take-home methadone and buprenorphine may ensure better adherence to HAART in individuals infected with human immunodeficiency virus (HIV) through injection drug use (IDU)., Design: Longitudinal data on adherence, opioid substitution treatment (OST) and patient behaviours starting from their first HAART prescription were collected for 276 individuals HIV-infected through drug use (n=1558 visits)., Setting: Out-patient hospital services delivering HIV care in Marseilles, Avignon, Nice and Ile de France., Measurements: At any given visit, patients were classified both according to the type of OST received and ongoing injection. Patients who reported no injection and no OST over the whole study period were considered as 'abstinent' and used as a reference category. A logit model based on generalized estimation equations (GEE) was used to identify predictors of non-adherence., Findings: After adjustment for alcohol consumption, depression and self-reported side effects, patients ceasing injection during OST and abstinent patients exhibited comparable adherence. Patients reporting injection, on OST or not, had a twofold and threefold risk, respectively, of non-adherence compared with abstinent patients (P<0.01 linear trend). Duration on OST without injecting was associated significantly with virological success., Conclusions: Both access to and effectiveness of OST contribute to sustaining adherence to HAART in HIV-infected IDUs. These results advocate strongly the need of wider use of OST in countries scaling-up HAART where HIV is driven by IDUs.

Introduction: Anhedonia is defined as the loss of the capacity to feel pleasure and there is no consensus with its relationship with depressive symptomatology. Furthermore, no study has investigated the problematic of anhedonia in the context of HIV-infection, which concern a lot of patients with depressive symptoms. Depressive symptomatology presents a major challenge in the management of HIV-infection due to its central role in clinical progression., Objective: This study aims to disentangle relationship between determinants of anhedonia, depression and anxiety in order to optimise mental management of HIV infection., Method: In 2003, a face-to-face survey (ANRS-EN12-VESPA) was conducted among patients selected in a random stratified sample of 102 French hospital departments delivering HIV care. Eligible respondents were HIV-infected outpatients, aged 18 or older living in France and diagnosed for at least six months. Among solicited patients, 2932 agreed to participate (response rate: 59%) and data about anhedonia, anxiety and depression are available for 1427 patients. The face-to-face gathered information on sociodemographic characteristics, such as education level, gender, partner, children, financial situation or housing and also psychosocial and sociobehavioural characteristics, such as drug use. Self-reported side effects of treatment were also available., Assessment Tools: Anxiety and depression were assessed using the hospital anxiety and depression (HAD) scale. Physical anhedonia was assessed using the French version of the Chapman scale. Three regression models were used to identify factors associated with anhedonia, anxiety and depression among demographic, psychosocial and clinical characteristics., Results: Factors independently associated with anhedonia were older age (>50), lower education level, unemployment and men HIV contaminated by heterosexual relation or injecting drug use. Women, with lower education level, unemployment, without steady partner, with a detectable viral load and who reported side effect of HAART presented more frequently anxiety. Unemployment, uncomfortable housing, no social support from friends, self-reported side effect and lipodystrophy were independently associated with depression., Conclusion: Our results underline the multiplicity of factors associated with mental disorders related to depression. These results can be explained by the fact that the anxiety and anhedonia are two cardinal symptoms of depression. Determinants of anhedonia and anxiety reported in this study may provide the key to a more exact delineation of depressive disorders in the context of HIV infection in order to optimize long-term psychological follow up of concerned patients.

Objectives: We studied the evolution of the patient-provider relationship (PPR) in HIV-infected patients who reported trustful relationships at highly active antiretroviral therapy (HAART) treatment initiation., Methods: Psychosocial and clinical data were obtained from the French ANRS CO-8 cohort. Break of trust was defined using the question "How much do you trust the provider who usually treats you at this clinic?" Predictors of a possible break of trust during the 5 years after initiating treatment for those patients reporting a trustful PPR at month 0 were identified using a Cox model., Results: During a total follow-up of 3,044 person-years, 68 (7%) patients reported having at least 1 break of trust in their PPR. Break of trust is independently associated with younger age, dissatisfaction with medical staff's explanations, cigarette smoking, and self-reported side effects and is independently inversely associated with severe HIV-related events and changes of treatment., Conclusions: A patient's break of trust in his provider is relatively infrequent. Accounting for the influence of immunologic status and psychosocial factors, self-reported side effects are shown to be detrimental to the PPR. Interestingly, clinical events and changes of treatment prevent a possible break of trust by reinforcing the provider's role. These results underline the importance of recognizing a patient's perceived secondary effects and developing appropriate care.

In the era of highly effective anti-retroviral therapy (ART), data show a significant difference in treatment outcomes between injecting drug users (IDUs) and non-IDUs. Factors that may contribute to suboptimal treatment outcomes in IDUs include delayed access to ART, competing comorbid diseases, psychosocial barriers and poor long-term adherence to ART. This review describes and compares several studies on adherence to ART and its correlates in HIV-infected individuals in general, then IDUs and finally those IDUs on opioid substitution treatment (OST). It highlights how ongoing drug use or OST can modify the pattern of these correlates. The aim is to extend all the experience acquired from these studies in order to optimise both access to care and adherence in those countries where HIV infection is mainly driven by IDUs and where ART and OST are only starting to be scaled up. The role of OST in fostering access to care and adherence to ART together with the promising results achieved to date using modified directly observed therapy (DOT) programs for patients taking methadone, allow us to emphasize the efficacy of a comprehensive care model which integrates substance dependence treatment, psychiatric treatment, social services, and medical treatment. The review concludes by suggesting areas of future research targeted at improving the understanding of both the role of perceived toxicity and patient-provider relationship for patients on ART and OST.

Background: The long-term efficacy of Highly Active Antiretroviral Therapies (HAART) has enlightened the crucial role of health-related quality of life (HRQL) among HIV-infected patients. However, any analysis of such extensive longitudinal data necessitates a suitable handling of dropout which may correlate with patients' health status., Methods: We analysed the HRQL evolution over 5 years for 1,000 patients initiating a protease inhibitor (PI)-containing therapy, using MOS SF-36 physical (PCS) and mental (MCS) scores. In parallel with a classical separate random effects model, we used a joint parameter-dependent selection model to account for non-ignorable dropout., Results: HRQL evolved according to a two-phase pattern, characterized by an initial improvement during the year following HAART initiation and a relative stabilization thereafter. Immunodepression and self-reported side effects were found to be negative predictors of both PCS and MCS scores. Hepatitis C virus coinfection and AIDS clinical stage were found to affect physical HRQL. Results were not significantly altered when accounting for dropout., Conclusion: Such results, obtained on a large sample of HIV-infected patients with extensive follow-up, underline the need for a regular monitoring of patients' immunological status and for a better management of their experience with hepatitis C and HAART.

We explored associations between time perspective (TP) and quality of life (QOL) among HIV-infected patients. With the French validated version of the Zimbardo Time Perspective Inventory, we evaluated the TP of patients. A self-administered questionnaire gathered information about QOL (WHOQOL-HIV), TP, relationship with medical staff and self-reported side effects of HAART. Six scores of QOL - physical, psychological, social relationship, environment, patient independence and spirituality were used as dependent variables in the linear regressions to identify factors associated with QOL. The sample (n=72) for this study was recruited from a hospital department specialising in HIV care and consisted of 48 (67%) HIV-infected women and 24 (33%) HIV-infected men with a mean age of 42 years. Using hierarchical regression analysis adjusted on socio-demographic characteristics, clinical characteristics and co-factors, significant relationships were observed between the several TP orientations and an impaired physical, environmental QOL as well as level-of-independence QOL. Specific dimensions of QOL are influenced by specific orientations of TP, which provides information on self-perception and subjective evaluation of QOL. The TP construct provides keys to managing HIV infection in order to improve QOL.

Background: This study aimed to determine factors associated with higher levels of health related quality of life (HRQL) among individuals HIV-infected through drug injection and to evaluate the impact of injecting drug status and opiate substitution treatment (OST) on HRQL., Methods: Two hundred and forty-three patients, enrolled in the MANIF cohort of patients HIV-infected through IDUs, participated. They completed a self-administered questionnaire, which included an HRQL evaluation (SF-12) and socio-demographic/clinical characteristics at the 42-month visit. Injecting drug status, OST and experience of negative life events (NLE) were collected at any follow-up visit in order to reconstitute individual trajectories., Results: Among the 243 patients, 35% reported a normal mental HRQL and 37% a normal physical HRQL. Independent predictors of "normal" mental HRQL were social support from partner, being a former IDU, no experience of violence-related NLE and few self-reported HAART-related side effects. "Normal" physical HRQL was predicted by younger age, stable partner, being a former IDU (> or = 6 months), CD4 cell count > 500, no experience of financial-related NLE and few HAART self-reported side effects., Conclusions: As HRQL has been found to have a prognostic value on the survival of HIV patients infected through drug injection, then providing more comprehensive care (for example by paying more attention to patients' experience of stressful events, meeting their needs in psychosocial support and better management of perceived toxicity) could globally improve treatment outcomes in this vulnerable population.

Background: Depression is common in HIV-infected patients receiving antiretroviral therapy. However, longitudinal studies addressing the role that depression might play in HIV clinical progression and mortality remain rare. This is especially true for those studies that also consider the possible confounding influence of patient's adherence to treatment., Methods: The ANRS CO-8 APROCO-COPILOTE cohort study enrolled 1,281 individuals at the initiation of a protease-inhibitor-containing regimen between 1997 and 1999. Adherence, depressive symptoms and other psychosocial factors were measured using self-administered questionnaires. Predictors of progression to AIDS or death were studied using Cox models., Results: Out of 1,028 individuals eligible for the present analysis, 92 individuals either died or had an AIDS-defining event during a median follow up of 54 months. At baseline, 377 individuals (41%) reported depressive symptoms and 124 (12%) reported non-adherence at month 4. Depressive symptoms at baseline were associated with progression (hazard ratio [HR] 2.1; P = 0.001). Despite the association between depressive symptoms and nonadherence, depressive symptoms remained a predictor of clinical progression (adjusted HR [aHR] [95% confidence interval (CI)] 1.6 [1.0-2.5]) after adjustment for several factors: initial non-adherence (aHR [95% CI] 2.0 [1.1-3.6]), having a steady partner (aHR [95% CI] 0.5 [0.3-0.7]), older age (aHR [95% CI] 1.40 [1.12-1.74] per 10-year increment), HIV clinical stage C (aHR [95% CI] 2.5 [1.6-4.0]), plasma HIV RNA > or = 100,000 copies/ml (aHR [95% CI] 1.7 [1.1-2.87]) and more than 8 years since HIV diagnosis (aHR [95% CI] 1.8 [1.1-2.8])., Conclusion: Depressive symptoms and non-adherence are independent predictors of HIV clinical progression and mortality. Screening and appropriate treatment of depressive symptoms at antiretroviral treatment initiation should be included in the standard care of HIV-infected patients.

Objectives: Benefits from HAART may be heterogeneous across people living with HIV. We measured the differences in the rate of HAART failure across the various subgroups represented at the level of a country., Design: We used data from a national representative sample of people living with HIV and followed at hospital in France (ANRS-EN12-VESPA Study)., Methods: Analyses were restricted to 896 participants on HAART for 6 months or more, who were antiretroviral naive at HAART initiation. Different indicators of treatment failure were defined: immunological failure (absence of an increase of 100 CD4 cells/microl or more); immunovirological failure (CD4 cell count of 200 cells/microl or less and detectable HIV-RNA); clinical failure (occurrence of an AIDS-defining illness more than 3 months after HAART initiation). Differences in the frequency of treatment failure were measured using logistic regression models adjusted for major established determinants of response to HAART., Results: Overall, 19.6% of the study participants experienced immunological failure, 3.4% immunovirological failure, and 3.0% clinical failure, with substantial variations across the various subgroups. Compared with homo/bisexual men, migrants had higher rates of immunological failure (adjusted odds ratio 2.27, 95% confidence interval 1.14-4.56 for migrant men and 2.19, 1.17-4.08 for migrant women), immunovirological failure (8.23, 1.77-38.33 and 6.91, 1.03-46.32), and clinical failure (4.60, 1.01-20.86 and 4.22, 0.84-21.17)., Conclusion: In France, migrants consistently appear to be at increased risk of treatment failure compared with other people with HIV. Understanding the reasons underlying such heterogeneity in terms of living conditions and educational/cultural background will be important.

Current socio-behavioural research in HIV-infected people has tried to identify patients with "high-risk" profiles, i.e. who simultaneously exhibit non-adherence to highly active anti-retroviral therapy (HAART) and unsafe sex with serodiscordant partners. We challenged this approach by investigating the correlates of both behaviours, for homosexual men, heterosexual men and heterosexual women separately, among a representative sample of 4963 HIV-infected people in France. Variables introduced in the analysis dealt with patients' background and daily life, with a focus on situations of economic, social and personal vulnerability. Overall, 2932 patients agreed to participate, and 1809 were both receiving HAART and sexually active. Among heterosexual women, non-adherence and unsafe sex appeared as joint outcomes of similar situations of vulnerability. Among heterosexual men, these behaviours were weakly correlated and shared some predictors related to situations of vulnerability. Among homosexual men, non-adherence and unsafe sex were not correlated and had distinct determinants. Situations of vulnerability, the context and the motives of unsafe sex, as well as factors associated with non-adherence and unsafe sex varied greatly with gender and sexual preference. Theoretical models used for designing behavioural interventions should take into account this diversity.

Background: The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi., Methods: We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat., Findings: Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (<80%) in the past 4 days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9-15.6)., Interpretation: These data show that large numbers of people can rapidly benefit from antiretroviral therapy in rural resource-poor settings and strongly supports the implementation of such large-scale simplified programmes in Africa.

This study aimed to identify factors associated with nonadherence during the maintenance phase of highly active antiretroviral therapy (months 12-60) in the Anti PROtease Cohort (APROCO) cohort after correcting for the bias due to missing outcome data. A Heckman 2-stage approach (generalized estimating equations probit model) was used to compare visits with moderate or poor adherence and visits with high adherence. Between months 12 and 60, at least 1 self-reported adherence measure was available for 970 of the 1110 patients with at least 12 months of follow-up (3889 visits with adherence assessments). Adherence was rated as high at 2466 visits, moderate at 1125, and poor at 298. After adjustment for "missingness," moderate and poor adherence were independently associated with age (younger), perceived treatment side effects, dosing frequency different from twice daily, and a protease inhibitor-based regimen. They were also associated with depression and lack of support from the main partner. High adherence was most likely among patients born outside the European Union. A comparison restricted to poor-adherence and high-adherence visits yielded a similar pattern of predictors. Adjusting for missing outcome data changed the predictor set. Reasons for nonadherence are multifactorial. Psychosocial interventions and the selection of the best-tolerated regimens are needed to improve long-term adherence of HIV-infected patients to their lifelong treatment.

This study investigated patterns of HIV disclosure to significant others (parents, siblings, children, other relatives, friends and colleagues) and describe them in terms of socio-demographic background and other characteristics, including experiences of AIDS-related discrimination. It also assessed the relationship between disclosure patterns and adherence to HAART. We used a cross-sectional survey conducted among a national representative sample of 2,932 HIV-infected people recruited in French hospitals. HIV disclosure patterns were both selective and cumulative: disclosure was more frequent for friends and siblings, while concealment prevailed concerning children, other relatives, and colleagues; but patients who disclosed their seropositivity to one significant other were also more likely to disclose it to other significant others. Patients reporting experiences of discrimination from sexual partners were less likely to be highly adherent, and we also found a significant relationship between uncontrolled disclosure and non-adherence. Patients who have opted for concealment probably consider non-adherence and uncontrolled disclosure as competing risks, but among them a significant minority loses on both counts. Counselling provided to HIV-infected people should not separate the adherence and disclosure issues, and adherence interventions should seek to help patients to manage concurrently disclosure/concealment of their seropositivity and its consequences.

During 2 periods between 1997 and 1999, the Aproco-Copilote (ANRS CO 008) cohort enrolled all HIV-infected patients who began antiretroviral therapy containing a PI in 47 French centers and who volunteered to participate (1281 patients) in order to describe and analyze their long-term clinical course and the benefits of treatment. Complete adherence (more than 95% of drugs actually taken) during the first 4 months of therapy appears crucial in maintaining virological response to therapy over time. Adherence depends on how patients experience the treatment but also on external factors such as their relationship with physicians and social workers. Virological failures were classified in two groups: those sensitive to the PI prescribed and related to poor adherence (no detectable PI) or patients with resistance related to pharmacokinetic issues (detectable but insufficient PI levels). Between April 1997 and May 2004, 118 patients died, and 188 episodes of AIDS and 1178 other severe events were recorded. Follow-up at 5 years was estimated at 90% and the probability of progression towards a new episode of AIDS 16%. Risk of AIDS onset was greatest during the first year and declined thereafter. Severe morbidity unrelated to AIDS or the side effects of treatment was frequent and gradually predominated. The only patients for whom AIDS was the most frequent severe morbidity were those who started treatment with CD4 cell counts < 50/mm3. The cumulative probability of a serious antiretroviral-induced adverse event (mainly hypertransaminasemia) was 30% at 5 years; 2/3 of these events occurred during the first 6 months of follow-up. Factors associated with the 169 events attributed to the first PI prescribed included: plasma HIV RNA >100,000 copies/ml, increased transaminase levels, creatinine clearance <70 ml/min, HCV or HBV co-infection, and prescription of indinavir. Other studies are underway on the associated factors specific to each of the events to delineate the respective roles of the virus, the treatments and other factors.

The aim of this study was to investigate factors associated with better health-related quality of life (HRQL) during the first three years after starting PI-containing antiretroviral treatment. Clinical, social and behavioural data from the APROCO cohort enabled us to analyze simultaneously the association between HRQL and patients' relationships with their health care providers. A self-administered questionnaire collected information about HRQL (MOS-SF36) and relationships with medical staff (trust and satisfaction with information). Two aggregate scores, the physical (PCS) and mental (MCS) component summaries (adjusted for baseline HRQL), were used as dependent variables in the linear regressions to identify factors associated with HRQL. We had complete longitudinal data for 360 of the 611 patients followed through M36. Factors independently associated with a high MCS were (male) gender, no more than one change in treatment, (few) self-reported symptoms and trust in the physician. Factors independently associated with high PCS levels were employment, no children, (few) self-reported symptoms and satisfaction with the information and explanations provided by the medical staff. These results underline the need to improve patient-provider relationships to optimize long-term HRQL. Socio-behavioural interventions should focus on this goal.

Here we review the available evidence on adherence to highly active antiretroviral therapy (HAART) and its relationship with the risk of the dissemination of HIV-resistant viral strains in both developed and developing countries. We argue that referring to these issues of resistance and adherence to withhold or delay access to HAART in developing countries implicitly imposes a double standard of thinking that is unacceptable. Scaling-up access to HAART to succeed in low-resource settings, however, requires the long-term monitoring of adherence as well as the clarification of the complex trade-offs between minimizing the costs of therapeutic regimens and minimizing the risks of non-adherence and resistance.

Objective: To assess the impact of different patterns of adherence to highly active antiretroviral therapy (HAART), in particular, the relative impact of early and late adherence, on long-term immuno-virological response in HIV-infected individuals started on a protease inhibitor-containing regimen., Design: Clinical, immuno-virological and self-reported adherence data were collected at 4 (M4), 12 (M12), 20 (M20), 28 (M28) and 36 (M36) months after HAART initiation in the French APROCO cohort., Methods: A standardized self-administered questionnaire classified patients as non-adherent, moderately or highly adherent at each visit. Stable viral suppression at both M28 to M36, and a CD4 cell increase > 200 between M0 and M36 were used as outcome measures., Results: Of the 582 patients followed regularly through M36, 360 patients had complete adherence data. Although 59.2% were highly adherent at M4, only 25.8% maintained consistent high adherence throughout the follow-up. High adherence at M4 was independently associated with both stable viral suppression at M28-M36 [OR (95% CI): 2.8 (1.4-5.5)] and a CD4 cell increase > 200 during the same period [OR (95% CI): 3.9 (1.7-9.7)]. However, 'moderately adherent' patients between M12 and M36 had the same likelihood [OR (95% CI): 1.9 (1.1-3.2)] as patients who were always high adherent [OR (95% CI): 1.9 (1.1-3.2)] of achieving stable viral load suppression, relative to those who reported non-adherence episodes., Conclusion: Optimizing adherence in the early months of treatment is crucial to ensure long-term immuno-virological high adherence during follow-up have a less negative impact. Priority should be given to interventions aimed to improve adherence in the early months of HAART.

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 <> 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 <>, 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 <> AIDS public policies without losing the potential for innovations that the fight against this epidemic has introduced in health care and <> systems, as well as physician-patient's relationships.

Purpose: The objective was to evaluate the impact of an intervention for improving adherence to antiretroviral therapies (HAART) in HIV-infected patients., Method: We designed a prospective, controlled, randomized trial to assess the impact of an educational and counseling intervention in addition to standard of care. At M0, the study enrolled 244 HAART-treated patients who attended a medical consultation between September and December 1999 who were not included in another protocol. Patients in the intervention group (IG) were offered three individual sessions by trained nurses. The proportions of adherent patients at 6 months followup (M6) and the change in HIV RNA between M0 and M6 were measured., Results: Between M0 and M6, HIV RNA significantly decreased in the 123 patients of the IG (mean difference = -0.22 log [+/-0.86], p =.013), while it increased (+0.12 log [+/-0.90], p =.14) in the 121 patients of the control group. However, the proportion of patients with HIV RNA <40 copies/mL remained similar in both groups. In an intent-to-treat analysis, the only significant predictor of 100% adherence at M6 was the intervention group (p =.05) after adjustment for baseline adherence (p =.001). Among the 202 patients with available data on adherence, the proportion of adherent patients was similar in both groups at M0 (58% vs. 63%, p =.59) but became higher in the IG at M6 (75% vs. 61%, p =.04)., Conclusion: The educational and counseling intervention was efficient for increasing adherence to HAART and could be implemented in most clinical settings.

The study, carried out in the French MANIF 2000 cohort of HIV positive patients contaminated through injecting drug use, assessed the impact of patients' sociodemographic and psychological characteristics, behaviors toward drug abuse, and antiretroviral treatment characteristics on the maintenance of adherence to HAART (highly active antiretroviral therapies). A total of 96 patients (30 men and 66 women), who were initially adherent at their first visit after HAART prescription, were considered for analysis. Among these 96 patients, 22 (22.9%) experienced adherence failure defined as a self-reported, non-adherence behavior at any visit before the 18th month of treatment. Logistic regression showed that lack of a stable relationship, active drug injection, and depression were independently associated with adherence failure. Patients' counseling for facilitating maintenance of adherence to HAART over time should focus on prevention of drug use, provision of social support and consider the potential impact of difficulties with treatment on psychological well-being.

Objective: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health-related quality of life (HRQL)., Methods: Medical data for patients in the French APROCO cohort were collected at enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey) and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a "normal HRQL." RESULTS. Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm, time since HIV diagnosis <8 years, undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12., Conclusion: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long-term strategies properly and to optimize the durability of response to antiretroviral therapy.

The authors tested the impact of social instability on adherence to highly active antiretroviral therapy (HAART) among patients infected with HIV through injection drug use (IDU; MANIF2000 cohort). In the study, they analyzed sociodemographic baseline characteristics to develop an indicator of social instability. Information concerning adherence to HAART was collected through questionnaires during a 2-year follow-up period. Factors associated with nonadherence were studied in two different groups: 1) patients who had stopped injection drug use (ex-IDUs) and who were not in drug maintenance programs (DMT) during the entire follow-up period, and 2) those who were still opiate dependent. Among the 210 eligible patients, 114 were classified as ex-IDUs and 96 as opiate dependent. Ex-IDUs reported nonadherence behaviors in 96 of 384 visits (25.0%), while opiate-dependent patients were nonadherent in 111 of 308 visits (36.0%; p = .02). Among ex-IDUs, the only factor associated with nonadherence was social instability, while among opiate-dependent patients, injection behavior was the only determinant of nonadherence behavior. For opiate-dependent patients, DMT may enhance adherence to HAART, but only if it is successful in reducing abuse of injection practices. For ex-IDUs, it is very important that the management of social difficulties be taken into account to increase adherence to HAART.

To-date, most socio-behavioural research about HTV-infected patients' adherence to highly active antiretroviral therapies (HAART) has been based on cross-sectional studies. The French APROCO cohort gave us the opportunity to conjointly analyse the relationships between short-term adherence to HAART and HIV-infected patients' characteristics before initiation of treatment on the one hand, factors related to patients' subjective experience with HAART on the other hand. At the fourth-month follow-up visit (M4) after first prescription of HAART (M0), 26.7% of our sample of 445 patients self-reported non-adherence behaviour. Some patients' characteristics at M0 (younger age, poor housing conditions, lack of social support, and problems of adherence with previous antiretroviral regimens) were related to non-adherence at M4 in multivariate analysis. Non-adherence at M4 was, however, also related to the evolutions that affected a number of factors between M0 and M4: levels of depression, symptoms associated with treatment side effects, perception of individual state of health, beliefs towards effectiveness and toxicity of HAART. increases in alcohol and tobacco consumption, as well as contacts with other physicians than hospital HAART prescribers. Our prospective study brings additional evidence that even short-term 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. It suggests that a dynamic approach to adherence, continuously monitoring the impact of experience with HAART on patients' daily lives, is needed for improving management of HIV/AIDS care.

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Objectives: Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20-month period and its relationship with virologic success., Methods: Self-reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitor-containing regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined., Results: Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was "always," 225 (51.6%) "sometimes," and 74 (17.0%) "never" "highly adherent" during follow-up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64-5.58]) or sometimes (OR [95% CI], 2.15 [1.24-3.74]) "highly adherent.", Conclusion: Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

To evaluate the impact of injection drug users (IDUs) adherence on effectiveness of highly active antiretroviral therapy (HAART), repeated measures of plasma viral load and CD4+ counts before HAART initiation and at last visit in the cohort were studied. Data were collected by means of patient's face-to-face and self-administered questionnaires about adherence to HAART during the week prior to the last visit. Of a total of 119 patients treated with HAART, undetectable viral load was obtained for 55 patients (46.2%) (G3); 34 patients (28.6%) (G2) had a viral load decline > 0.5 log copies/ml but still detectable viral load at last visit in the cohort, while 30 patients (25.2%) (G1) had no decline or decline

Purpose: The purpose of our study was to assess short-term self-reported symptoms in patients who were started on two nucleoside reverse transcriptase inhibitors and one protease inhibitor (PI) in the multicenter APROCO cohort (N = 336) and to assess the influence of these symptoms on adherence., Method: Adherence and patient's reported symptoms were measured at 1 and 4 months (M) after initiation of highly active antiretroviral therapy (HAART) through self-administered questionnaires., Results: Most patients reported at least one symptom (94.0% at M1; 88.0% at M4); fatigue and diarrhea were the most often reported symptoms. Respectively, 81.3% and 75.0% of patients were strictly adherent to HAART during the 4 days prior to M1 and M4 visits. After adjustment for younger age, history of antiretroviral treatment, unstable housing, poor social support, and alcohol consumption, patients who reported a high number of symptoms at M1 were more likely to be nonadherent at M4 (odds ratio per symptom = 1.13; 95% CI = 1.03-1.24)., Conclusion: Patients reporting a high number of symptoms soon after HAART initiation are at higher risk of future nonadherence and could be targeted for interventions to achieve good levels of adherence and to improve treatment outcome.