In the past years, we observed a sharp increase of Syphilis, especially among male who have sex with male (MSM), either HIV-infected, or on pre-exposure prophylaxis (PrEP). Our aim was to assess ...syphilis prevalence and incidence among people living with HIV (PLWH) and PrEP users.
PLWH were included from 2010 to 2020 and PrEP users from 2016 to 2020 from the Dat'AIDS French cohort. We calculated syphilis prevalence and incidences for first infections, re-infections, and iterative infections (> 2 times). T-Tests, Wilcoxon tests and Chi2 test were used for descriptive analysis and multivariate logistic regression models were used to estimate Odds ratios (OR) and 95% confidence intervals (95% CI) for factors associated with syphilis.
Among the 8 583 PLWH, prevalence of subject with past or present syphilis was 19.9%. These subjects were more likely MSM or transgender and aged over 35 years, but prevalence was lower in AIDS subjects. Same pattern was seen for incident infection and re-infection. Incidence was 3.8 per 100 person-years for infection and 6.5 per 100 person-years for re-infection. Among 1 680 PrEP users, syphilis prevalence was 25.8%, with an estimated 7.2% frequency of active syphilis. Risk of syphilis infection was higher in male and increased with age. Incidence was 11.2 per 100 person-years for infection and 11.1 per 100 person-years for re-infection.
Syphilis prevalence and incidence were high, especially in older MSM with controlled HIV infection and PrEP users, enhancing the need to improve syphilis screening and behavioral risk reduction counseling among high-risk subjects.
As HIV-infected adults on successful antiretroviral therapy (ART) are expected to have close to normal lifespans, they will increasingly develop age-related comorbidities. The objective of this ...cross-sectional study was to compare in the French Dat'AIDS cohort, the HIV geriatric population, aged 75 years and over, to the elderly one, aged from 50 to 74 years. As of Dec 2015, 16,436 subjects (43.8% of the French Dat'AIDS cohort) were aged from 50 to 74 (elderly group) and 572 subjects (1.5%) were aged 75 and over (geriatric group). Durations of HIV infection and of ART were slightly but significantly different, median at 19 and 18 years, and 15 and 16 years in the elderly and geriatric group, respectively. The geriatric group was more frequently at CDC stage C and had a lower nadir CD4. This group had been more exposed to first generation protease inhibitors and thymidine analogues. Despite similar virologic suppression, type of ART at the last visit significantly differed between the 2 groups: triple ART in 74% versus 68.2%, ART ≥ 4 drugs in 4.7% versus 2.7%; dual therapy in 11.6% versus 16.4% in the elderly group and the geriatric group, respectively. In the geriatric group all co-morbidities were significantly more frequent, except dyslipidemia, 4.3% of the elderly group had ≥4 co-morbidities versus18.4% in the geriatric group. Despite more co-morbidities and more advanced HIV infection the geriatric population achieve similar high rate of virologic suppression than the elderly population. A multidisciplinary approach should be developed to face the incoming challenge of aging HIV population.
Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of ...single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART.
Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat'AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM).
Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11).
First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.
We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to ...compare them with those in the French general population. These cancers are targeted by the national cancer-screening program.
This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort.
Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection.
The 2010-2015 CRC incidence rate was 25.0 95% confidence interval (CI): 18.6-33.4 per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73).
The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.
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.
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.
Introduction We examined comorbidities, comedications and polypharmacy among people living with HIV (PLHIV) and associated challenges with HIV antiretroviral therapy (ART). Methods A cross-sectional ...design was used in web-based surveys conducted during 2019 in France, Germany, Italy, and the UK. Pooled sample comprised 120 internists/infectious disease specialists managing ≥50 HIV patients, and 1171 adult PLHIV combined who participated in two separate surveys, the Positive Perspective Survey (n=483), and the Unmet Needs Survey (n=688). The outcomes were perceptions and behaviors towards ART based on PLHIV and healthcare provider (HCP) perspectives. Results According to HIV physicians, challenges associated with comedications were a major reason for their patients not starting ART, or stopping, switching, or skipping their HIV treatment after they started. In total, 16.8% of providers indicated that their patients had not started ART because of medical reasons/comorbidities that interfered with dosing (France 21.7%, Germany 15.4%, Italy 6.9%, and UK 24.1%). Other reasons cited by providers for patients not starting HIV treatment were: concerns about drug tolerability/ side effects (overall 34.6%, France 39.1%, Germany 34.6%, Italy 27.6%, and UK 37.9%); concerns about long-term toxicities (overall 26.2%, France 39.1%, Germany 26.9%, Italy 24.1%, and UK 17.2%), as well as concerns about drugdrug interactions (overall 16.8%, France 13.0%, Germany 26.9%, Italy 17.2%, and UK 10.3%). Averaged across all ART regimen types, the percentage of PLHIV in the Unmet Needs Study who indicated that they needed monitoring when taking other medications with their ART was 5.8%, 15.9%, and 24.1% among those with none, 1, or ≥2 non-HIV comorbidities, respectively. Within the Positive Perspectives Survey, overall prevalence of polypharmacy was 38.8% (France 41.9%,Germany 24.2%, Italy 40.8%, and UK 48.0%). Compared to those without polypharmacy, those reporting polypharmacy had lower odds of reporting viral suppression (adjusted odds ratio, AOR=0.40) and optimal overall health (AOR=0.65); they were however more likely to be worried about taking more medicines as they grew older (AOR=2.15), and to be more concerned how their ART might affect other medicines they took (AOR=2.35) (all p<0.05). Conclusions A significant unmet need remains for PLHIV relating to co-management of comorbidities and associated challenges such as polypharmacy. Polypharmacy was associated with suboptimal self-rated health and concerns about the risk of long-term negative impacts from ART intake. Holistic care that provides simplified regimens to medically complex patients can help improve treatment outcomes.
The WHO 95-95-95 targets for 2030 do not imply that people living with HIV (PLHIV) achieve a good quality of life. The current 30-day dispensing interval for antiretroviral (ART) burdens the ...healthcare system. Lengthening dispensing intervals could alleviate this burden as well as enhance patient well-being.
To capture perceptions on 90-day dispensing interval (90D) for ART from the perspective of PLHIV, people on pre-exposure prophylaxis (PrEP), doctors, and pharmacists.
Multi-centre observational survey led in France from 16 to 20 October 2020, among doctors agreeing to participate via regional coordinated care organisations for HIV, all PLHIV or people on PrEP consulting these outpatient-clinic doctors, and pharmacists doing ART dispensing.
The survey was completed by 220 doctors who saw 1087 people (999 PLHIV; 88 on PrEP) and 176 pharmacists from 55 centres. Among the PLHIV, 855 (85.6%, 95% CI: 83.2%-87.7%) and among the patients on PrEP, 70 (79.5%, 95% CI: 69.6%-87.4%) stated they would be interested in 90D. All in all, patients who were more likely to endorse 90D are those who opt exclusively for hospital dispensing (OR 3.22 1.57-6.58) and who rotate between hospital and community pharmacy dispensing (OR 3.29 1.15-9.32). Patients who were less likely to endorse 90-D were those who consult in a city located outside the 3 French high HIV prevalence regions (OR 0.66 0.44-0.99), receive 2 vs 1 pill QD regimens (OR 0.53 0.31-0.91), and anticipate at least one vs no limitation to 90D (OR 0.27 0.17-0.42). 90D was perceived as possible by 152 pharmacists (86.4%), including 8 (5%) without restriction, and 219 doctors (99.6%), including 42 (19.2%) regardless of PLHIV's immunovirologic status or social conditions (health insurance coverage, access to housing or accommodation, access to rights, resources). Comparison of the benefits and limitations of a 90-day ART dispensing interval as perceived by PLHIV and people on PrEP, doctors and pharmacists shows that doctors anticipate a higher number of benefits than people on ART and/or pharmacists, chiefly that 90D would be more convenient and create less risk of drug shortages and that patients would gain autonomy and a better quality of life. Pharmacists were found to clearly perceive the economic benefits (90D would be less expensive) but anticipate more drawbacks than doctors and the people on ART themselves: more administrative burdens, more non-dispensing if doses get lost, harder to track adherence and more drug-drug interaction issues, and more work as they shall have to warn the patient of potential risks of shortages due to the cost of the stock.
A clear majority of PLHIV, people on PrEP, doctors, and pharmacists endorsed 90D of ART. Most patients thought that 90D would be a good option, whereas most pharmacists and doctors thought that eligibility for 90D dispensing should depend on immunovirologic factors and social condition criteria. Moreover, pharmacists thought it would be necessary to commit regulatory resources and a better follow-up on adherence and drug-drug interactions.
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