To study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART).
The APROCO/COPILOTE cohort enrolled patients initiating a protease ...inhibitor-containing ART in 1997-1999. The association between occurrence of first non AIDS-defining severe events (NADE) and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4), CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4< 500/mm3, CD4 > 500/mm3 and CD4/CD8 ratio < 1, CD4 > 500/mm3 and CD4/CD8 ratio > 1). Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion.
We included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2-11.4). Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2-0.5) at baseline and 0.6 (IQR: 0.4-0.9) after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%), cardiovascular events (14%) and cancers (10%). For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32-3.44).
CD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.
To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs).
Observational ...single-center study.
We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions.
A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65).
Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored.
In a context where the economic burden of HIV is increasing as HIV patients now have a close to normal lifespan, the availability of generic antiretrovirals commonly prescribed in 2017 and the ...imminence of patent expiration are expected to provide substantial savings in the coming years. This article aims to assess the economic impact of these generic antiretrovirals in France and specifically over a five-year period.
An agent-based model was developed to simulate patient trajectories and treatment use over a five-year period. By comparing the results of costs for trajectories simulated under different predefined scenarios, a budget impact model can be created and sensitivity analyses performed on several parameters of importance.
The potential economic savings from 2019 to 2023 generated by generic antiretrovirals range from €309 million when the penetration rate of generics is set at 10% to €1.5 billion at 70%. These savings range from €984 million to €993 million as the delay between patent and generic marketing authorisation varies from 10 to 15 years, and from €965 million to €993 million as the Negotiated Price per Unit (NPU) of generics at market-entry varies from 40 to 50% of the NPU for patents.
This economic savings simulation could help decision makers to anticipate resource allocations for further innovation in antiretrovirals therapies as well as prevention, especially by funding the Pre-Exposure Prophylaxis (PrEP) or HIV screening.
Our objective was to describe the clinical presentation of chikungunya virus (CHIKV) infection in patients living with HIV (PLHIV) during the 2014 Martinique outbreak. During the outbreak and the 6 ...following months, all PLHIV coming in our unit for a medical evaluation answered questions about potential CHIKV related symptoms, and had blood tests to assess the diagnosis. For patients coming in at the acute phase of infection, we are able to provide and analyze CD4+, CD8+ T-cells and HIV viral load evolution before, during and after CHIK infection. Among the 1 003 PLHIV in care in the center at the time of the outbreak, 188 (94 men and 94 women) had confirmed (following the WHO definition) CHIKV infection. Clinical presentation was common in 63% of the cases, severe and atypical forms were scarce. During the acute phase, CD4+ and CD8+ T-cells (evaluated in 30 PLHIV, 15 men and 15 women) absolute numbers dropped significantly, but returned to pre-CHIKV values after the acute phase. Reassuringly, CD4 and CD8 T cells proportions did not decrease during the acute phase. CHIKV infection had no significant impact on this anti-retroviral treated population.
The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients.
Patients were followed from seven large HIV reference centers in France that ...maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR ≤60 ml/min per 1.73 m² over ≥3 months. A Cox's model with delayed entry was used to search predictive factors of time to CKD.
From 1993 to 2006, 349 out of 7378 patients were found to have CKD. Of these, 166 had hypertension, 33 had diabetes, and 26 were antiretroviral therapy-naïve. Occurrence of acute kidney injury (hazard ratio HR = 2.40) and hypertension (HR = 2.39) were strongly associated with an increased risk of CKD. Patients with a durable level of CD4 count >200 cells/mm³ had a lower risk of CKD (HR = 0.63). Recent exposure to indinavir (HR = 2.03), totenofovir (HR = 1.55), and abacavir (HR = 1.37) were associated with an increased risk of CKD. Past exposure to tenofovir was also associated with an increased risk of CKD (HR = 2.23), and a trend toward significance was observed for past exposure to indinavir (HR = 1.28).
CKD was not rare in HIV-infected patients and occurs preferentially in HIV-infected patients exposed to certain ARVs, specifically abacavir, indinavir and tenofovir. This requires closer monitoring of renal function in patients exposed to one of these drugs.
The objective was to develop a multivariable prognostic index for overall mortality over a five-year span integrating classical HIV biomarkers and comorbidities in people living with HIV (PLHIV) aged ...60 or older.
Prospective multicenter cohort study from the French Dat'AIDS cohort.
All HIV-1 infected patients aged 60 years or older on 1st January 2008 were included. Sociodemographic data, CD4 cell count, CD4 nadir, HIV viral load, history of comorbidities, hepatitis co-infections and laboratory parameters at baseline were considered as potential prognostic variables. Primary outcome was all-cause mortality.
Among 1415 patients included, we derived a score comprising the following predictors: Age (65-74: 1 point; ≥75: 8 points), CD4 cell count (200-349: 3 points; <200: 6 points), non-HIV related cancer (6 points), cardiovascular disease (8 points), estimated glomerular filtration rate (30-59 mL/min/1.73m2: 5 points; <30mL/min/1.73m2: 16 points), cirrhosis (13 points), low body mass index (<18.5 kg/m2, 10 points), anemia (6 points). Mean observed score was 7.0 ± 8.0 and ranged from 0 to 45. Score categories defined 4 risk groups for mortality: low, moderate, high and very high risk (5-year survival probability 0.95 (95%CI0.93-0.97), 0.90 (95%CI0.87-0.92), 0.77 (95%CI0.68-0.84) and 0.54 (95%CI0.43-0.63) respectively). The score showed good discrimination (C-statistic = 0.76) and calibration.
We propose a multivariable prognostic score for mortality among PLHIV aged 60 or over, who will become the predominant population in future years in western populations. It could be a useful tool for research, for developing preventive and treatment strategies according to risk group, and for risk assessment by clinicians.
The Caribbean is the second most affected region in the world by human immunodeficiency virus (HIV), and HIV prevalence is significantly higher among persons in jails and prisons than in the free ...population. The aim of our study was to assess the screening rates of HIV, hepatitis B and C, syphilis and human T cell leukaemia virus type 1 among newly-arrived persons in 2014, at Ducos facility in Martinique and the testing process performance.
This is an observational monocentric study conducted within the prison's health unit. The study population consisted of all individuals incarcerated between 01/01/14 and 31/12/14. At the initial medical visit, HIV and STI testing were proposed to every newcomer. The rate of acceptance was calculated, as well as the screening process performance.
In 2014 778 new persons were incarcerated, among those, 461 (59.3%) were tested. The main reasons for missing the testing opportunity were due to organization of the judiciary system (persons on electronic monitoring or day parole, transferred or quickly released before completion of the process) or to individual refusal. Finally, 75 persons did not get their results (all of them negative), 41 of them due to the medical staff work overload.
HIV and STI testing rates among newcomers at Ducos have notable room for improvement. The future availability of combined (HIV, HBV, HCV and syphilis) rapid tests may be very useful in case of short term incarceration, if their cost is not prohibitive. Reaching higher levels of testing will also require more resources.
We investigated whether patients receiving selected antiretroviral combinations had a higher risk of chronic kidney disease (CKD) using traditional regression modeling and a causal approach in a ...large prospective cohort.
For the purpose of this study, we selected 6301 patients who (i) started their first antiretroviral regimen after 1st January 2004, (ii) had at least one serum creatinine measurement within 6 months before ART initiation (study entry), and (iii) had at least two measurements after study entry. Baseline eGFR was defined from the last serum creatinine measurement before study entry. All eGFR values were calculated using the Modification of Diet and Renal Disease (MDRD) equation. Both traditional Cox proportional hazards model and Cox marginal structural models were applied. Distinct coding for antiretroviral therapy exposure were investigated as well as double robust estimators.
Overall we showed that patients receiving tenofovir (TDF) with a ritonavir boosted protease inhibitor (rbPI) exhibited a higher risk of CKD compared with patients who received TDF with a non-nucleosidic reverse transcriptase inhibitor (NNRTI). Such an increased risk was observed considering both initial and current regimens. Our analysis revealed a clinician-driven switch away from TDF among persons experiencing a decline in renal function while receiving this drug.
Our results show that combination of TDF and boosted protease inhibitor is associated with a higher CKD risk than TDF and a NNRTI.
Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in ...HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients.
Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.
Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%).
Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.
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