Fidéline Collin

Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults.

In the ANRS CO8 APROCO-COPILOTE cohort of patients treated with combination antiretroviral therapy since 1997–1999, the incidence density of bone fractures was 3.3 for 1000 patient-years [95% confidence interval (CI) = 2.0–4.6]. The rate was 2.9-fold (95% CI = 1.3–6.5) higher among patients with excessive alcohol consumption and 3.6-fold (95% CI = 1.6–8.1) higher in those with hepatitis C virus (HCV) coinfection. Specific monitoring of HCV/HIV-coinfected patients and active promotion of alcohol cessation should be recommended for the prevention of bone fractures.

Simplification Therapy with Once-Daily Emtricitabine, Didanosine, and Efavirenz in HIV-1–Infected Adults with Viral Suppression Receiving a Protease Inhibitor–Based Regimen: A Randomized Trial

BACKGROUND We assessed a once-daily combination to simplify therapy in patients infected with human immunodeficiency virus type 1 (HIV-1). METHODS A total of 355 adults with plasma HIV-1 RNA levels <400 copies/mL were randomly assigned to either switch to once-daily emtricitabine, didanosine, and efavirenz (n=178) or maintain their protease inhibitor (PI)-based regimens (n=177). The primary end point was sustained suppression of plasma HIV-1 RNA levels to <400 copies/mL. RESULTS At week 48, the proportion of patients meeting the end point was 87.6% in the PI group and 90.5% in the once-daily group, with a treatment difference of -2.9% (upper bound of the 1-tailed 95% confidence interval, 2.6%). The proportion of patients with HIV-1 RNA levels <50 copies/mL was higher in the once-daily group (87%) than in the PI group (79%) (P<.05). Resistance mutations to efavirenz and emtricitabine were detected in all patients in the once-daily group who experienced virologic failure while receiving study medication. The proportion of patients discontinuing study medication because of adverse events was similar between the once-daily group (9%) and the PI group (10%) (P=.8). CONCLUSIONS Substituting a convenient once-daily combination of emtricitabine, didanosine, and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression.

Prevalence and Predictors of Deterioration of a Trustful Patient-Provider Relationship Among HIV-Infected Persons Treated With Antiretroviral Therapy

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 3044 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 staffs explanations, cigarette smoking, and self-reported side effects and is independently inversely associated with severe HIV-related events and changes of treatment. Conclusions:A patients 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 providers role. These results underline the importance of recognizing a patients perceived secondary effects and developing appropriate care.

Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

BACKGROUND Zidovudine, the first antiretroviral agent, has short-term haematological toxicity. However, it is unclear whether patients tolerating long-term zidovudine-containing regimens will benefit from a switch to non-zidovudine-containing regimens. METHODS One hundred and fifty-eight patients enrolled in the ALIZE trial receiving zidovudine at baseline were analysed. These patients were randomized to continue their regimen or to switch to a combination of emtricitabine, didanosine and efavirenz for 48 weeks. Changes from baseline in haemoglobin (Hb), neutrophil and platelet counts were compared between arms as well as the occurrence of cardiovascular events, bacterial infections, use of haematopoietic growth factors, blood transfusion and quality of life using the Medical Outcome Study HIV (MOS-HIV) health survey. RESULTS Eighty-one patients continued their regimen and 77 switched. At 48 weeks, mean change from baseline in Hb were +0.73 and -0.37 g/dL in the switch and maintenance groups, respectively (P < 0.01). Mean neutrophil counts increased by 592 and 51 cells/mm(3) in the switch and maintenance groups, respectively (P = 0.02). The occurrence of cardiovascular events or bacterial infections was similar in both treatment arms with no use of haematopoietic growth factors or blood transfusion. Also, mean change from baseline in MOS-HIV physical and mental health summary scores was similar in both arms. CONCLUSIONS A switch from a long-standing zidovudine- to a non-zidovudine-containing regimen modestly improves haematological parameters and is not associated with obvious clinical benefit.

New Highly Sensitive Real-Time PCR Assay for HIV-2 Group A and Group B DNA Quantification

ABSTRACT HIV-2 infection is characterized by a very low replication rate in most cases and low progression. This necessitates an approach to patient monitoring that differs from that for HIV-1 infection. Here, a new highly specific and sensitive method for HIV-2 DNA quantification was developed. The new test is based on quantitative real-time PCR targeting the long terminal repeat (LTR) and gag regions and using an internal control. Analytical performance was determined in three laboratories, and clinical performance was determined on blood samples from 63 patients infected with HIV-2 group A (n = 35) or group B (n = 28). The specificity was 100%. The 95% limit of detection was three copies/PCR and the limit of quantification was six copies/PCR. The within-run coefficients of variation were between 1.03% at 3.78 log10 copies/PCR and 27.02% at 0.78 log10 copies/PCR. The between-run coefficient of variation was 5.10%. Both manual and automated nucleic acid extraction methods were validated. HIV-2 DNA loads were detectable in blood cells from all 63 patients. When HIV-2 DNA was quantifiable, median loads were significantly higher in antiretroviral-treated than in naive patients and were similar for groups A and B. HIV-2 DNA load was correlated with HIV-2 RNA load (r = 0.68; 95% confidence interval [CI], 0.4 to 0.8; P < 0.0001). Our data show that this new assay is highly sensitive and quantifies the two main HIV-2 groups, making it useful for the diagnosis of HIV-2 infection and for pathogenesis studies on HIV-2 reservoirs.

Prolonged Medically Recorded Treatment Interruptions Among HIV-Infected Patients on Highly Active Antiretroviral Therapy With Controlled Viremia: When Physicians Have to Juggle Patient Negotiation and Guidelines

To the Editors: Treatment interruption (TI) strategy among HIV-infected patients on highly active antiretroviral therapy (HAART) is associated with deleterious immunologic outcomes, increased risk of virologic failure, and resistance emergence. Two major studies, Strategies for Management of Antiretroviral Therapy (SMART) and TRIVACAN, demonstrated in 2006 that TI led to a significantly higher risk of disease progression and death. Consequently, TIs are currently not recommended in patients on HAART; nevertheless, they still occur in routine practice. However, it is quite difficult to determine to what extent TIs are decided on by the physician or arise from a patient’s undisclosed act of treatment discontinuation. We used data from the ANRS CO8 APROCO-COPILOTE cohort to estimate the incidence of medically recorded TI and to identify their clinical and psychosocial predictors. The ANRS CO8 APROCO-COPILOTE is a cohort of patients started on a protease inhibitor-containing regimen between 1997 and 1999, collecting prospective clinical data by standardized medical records and sociodemographic and psychosocial data by self-administered questionnaires. All visits corresponding to the HAART maintenance period (Months M12–M96) for patients with controlled viremia (plasma HIV RNA less than 400 copies/mL) during the 12 months before the then current visit were included in the analysis. All episodes of TI (including multiple episodes for some patients) lasting at least 60 days were selected from the medical records. A history of viral rebound was defined as plasma HIV RNA greater than 400 copies/mL at least once before the 12 months of controlled viral load preceding the then current visit. The occurrence of HIV-related clinical events not related to HAART toxicity was recorded in the medical files. An extended Cox proportional hazards model for recurrent events was used to identify the clinical, sociodemographic, and psychosocial factors associated with TI. The multivariate model was built using a backward selection of explanatory variables. A period effect on TI occurrence was tested (pre-/ post-January 2006, corresponding to the circulation of recommendations against TI). All analyses were performed using Stata, Version 9 (Stata, College Station, TX). Among the 832 selected patients, accounting for 9595 visits and 3592 person-years, 96 patients experienced 106 TI (incidence rate [95% confidence interval] of 2.9 [2.4–3.6] per 100 personyears) during the 7-year study period. Median (interquartile range) duration of TI was 109 (84–157) days. Mean (standard deviation) CD4 cell count before TI was 690 (326) cells/mm. Median (interquartile range) individual CD4 loss during TI was 87 (0–204) cells/mm. In the multivariate model, a history of viral rebound and the number of HIVrelated clinical events were independently associated with lower probability of TI occurrence (Table 1). Patients who reported having a good patient–provider relationship or no social support from their main partner were more likely to experience TI. Neither a calendar period effect (pre-/post-January 2006) nor any interaction effect between the predictors and the calendar period were found. Moreover, no change in TI incidence was observed between the two periods. This is the first study exploring the incidence and predictors of medically recorded prolonged TI in HIV-infected patients on HAART with controlled viremia. Because short interruptions are highly inadvisable and not promoted by physicians, selecting long-term TI from medical records enabled us to focus on those TI potentially monitored by the physician and/or more likely to have resulted from an ‘‘agreement’’ between the patient and the physician. By choosing patients with prolonged controlled viremia during the HAART maintenance phase, we tried to select those for whom a TI would have been judged less risky by the physician. This study has highlighted a relatively small TI incidence rate among patients with controlled viremia. These individuals were usually off HAART for short periods (median duration of TI was less than 4 months). Although recommendations against TI were included in French HAART guidelines in 2006, no calendar period effect was observed in the present study, thereby confirming that these guidelines do not seem to influence the incidence or the pattern of TI predictors. We also tested the effect of the type of the antiretroviral regimen on the occurrence of TI, comparing currently used boosted protease inhibitor and other protease inhibitor regimens used in the late 1990s. This effect did not reach statistical significance in the multivariate analysis, showing also that no difference in the pattern of TI over time was found. The lack of social support from one’s main partner, which has already been reported as a determinant of nonadherence to HAART, remained associated with TI in the multivariate model. However, the association found between TI and both a low number of HIV-related clinical events and no history of viral rebound confirmed that these TIs occur in a population with a successful HAART history, in turn probably characterized by sustained adherence. Such long-term TIs in patients with controlled viremia are likely therefore to result either from physicians’ decision or from patients’ negotiations with their physicians leading to TI approval. Both situations engage physicians in an assessment of the risks and benefits associated with TI on an individual basis. Interestingly, a good patient–physician relationship is a further predictor of TI insofar as a good relationship is a necessary basis for possible negotiations about any medical decision