Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment

BACKGROUND: The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence. METHODS: Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence. RESULTS: A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence. CONCLUSIONS: At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members

Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy

Pathogens

IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm(3)) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Comment on: Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection, by Chelkeba L. et al

International audienc

Use of short message service in at-home COVID-19 patient management

International audienceBackground: Mobile health innovations are well adapted for ambulatory coronavirus disease 2019 (COVID-19) patients who risk clinical deterioration at home during the second week of illness.Methods: A short message service (SMS) communication program was implemented by French physicians to monitor COVID-19 patients after discharge from outpatient or emergency care. The aim of the SMS tracking is to advise patients about their need for medical reassessment if reporting worsening of COVID-19 symptoms. A follow-up via SMS to all confirmed positive patients in the Nîmes area (France) was established. Every morning, patients received four follow-up questions. Daily responses were converted to green, orange or red trees, analysed in real time by physicians. "Red" patients were called immediately to check their condition and organise transfer to hospital if needed. "Orange" patients were called within two hours to verify whether the specific instructions following the SMS had been followed.Results: From March 21 to June 30, 2020, 1007 patients agreed to sign up to the SMS tracking, 62% were women and the mean age was 41.5 years (standard deviation (SD) 16.0). During follow-up, 649 (64%) became "orange" and 69 (7%) "red". Ten patients were directly admitted to the Infectious Diseases Department during their follow-up due to clinical worsening, all but one as a result of SMS alerts and subsequent telephone assessment by physicians.Conclusion: SMS tracking platforms could be useful as an early warning system to refer patients with worsening clinical status to hospital-based care or additional clinician advice

Documented cutaneous loxoscelism in the south of France: an unrecognized condition causing delay in diagnosis

International audienceBACKGROUND:Loxoscelism is an envenomation due to a bite by spiders of the genus Loxosceles, very well known on the American continent but unrecognized in Europe.CASE REPORT:We report the case of a 36-year-old woman, without any medical history or treatment, who went to a University Hospital in the South of France, for a painful skin lesion on the internal part of her left thigh, which appeared in the morning and developed rapidly during the day. She was directed to the infectious disease department with a diagnosis of skin infection. In spite of the antibiotics, the lesion increased, with a hemorrhagic central blister, an irregular ecchymotic center, a pale perimeter, and an extensive inflammatory and indurate oedema affecting the whole thigh. There was also a low-grade fever, chills, intense pain and a generalized scarlatiniform exanthema. The lesion was finally diagnosed as cutaneous loxoscelism, then confirmed by collection and identification of a Loxosceles rufescens spider killed by the patient the morning of the occurrence of the lesion. Following an initial symptomatic treatment, the development of a necrotic ulcer justified a delayed surgical reconstruction, after stabilization of the lesion.CONCLUSIONS:Loxosceles bites are usually painless and rarely noticed by patients, often leading to a presumptive diagnosis. Therefore, in the case of a dermonecrotic lesion developing unfavourably with antibiotics, cutaneous loxoscelism should be one of the diagnoses to be considered

Exposure to HIV risks among young people who use drugs (YPUD) in three cities in Vietnam: time to develop targeted interventions

International audienceThe aim of this study is to identify the profiles of young people who use drugs (YPUD) and their exposure to HIV risks in the 3 main cities of Vietnam, Haiphong, Hanoi, and Ho Chi Minh City (HCMC), in order to design a community-based intervention to prevent HIV. Methods A survey using respondent-driven sampling (RDS) was conducted among YPUD aged 16–24. Participants were eligible if they reported drug use, confirmed by a urine test. After obtaining informed consent, they were screened for HIV/HCV and assessed using face-to-face questionnaires and self-report. A cluster analysis was conducted, taking into account risk behaviors and confirmed HIV-positive status. Results Seven hundred and three YPUD aged 16–24 were recruited between October 2016 and February 2017, 584 of whom were included in the final analysis. Median age was 21 (17.7, 23.0); 79% were male, 18% female, and 2% transgender. Methamphetamines use was reported by 77%, followed by cannabis (51%) and heroin (17%); polydrug use was common; 15% had “ever” injected drugs. HIV prevalence was 7%. Among all participants, 48% reported non-consistent condom use and 1% reported needle/syringe sharing during the previous month. Four distinct profiles of HIV risk behaviors were identified: The high multiple-risk group mixed unsafe drug use with unsafe sexual practices and had higher prevalence of HIV; the second group practiced high-risk sex with non-consistent condom combined with methamphetamine use; the third group was a moderate-risk group with limited unsafe sexual practices; and the fourth was considered at “low-risk” as reportedly, most never had sex and never injected. The highest risk group included more female YPUD, living in HCMC, who used heroin and had unsafe sex with their regular partners. The second high-risk group included most of the MSM and all transgender people and frequently reported mental health disorders. Conclusions The profiles of YPUD who are at risk of HIV vary according to age, location, and population group. Injecting YPUD are the most exposed to risk and need immediate attention. Sexual exposure to HIV is very common. Mental health is a major concern. Interventions need to be integrated in a differentiated but holistic approach

Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients

International audienceOBJECTIVES: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.METHODS: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time.RESULTS: At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)).CONCLUSIONS: None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients