Improving tuberculosis management in prisons: Impact of a rapid molecular point-of-care test.

OBJECTIVE: To improve tuberculosis (TB) diagnosis in prison, we evaluate the value of the XpertⓇMTB/RIF Ultra assay (Xpert) as point-of-care (POC) in a French prison hospital. METHODS: We first validated Xpert use on raw sputum at the referent laboratory. Secondly, trained physicians at the prison hospital performed Xpert tests for each patient presenting TB symptoms. The results were compared with Xpert, microscopic examination, culture and drug susceptibility testing on the corresponding decontaminated specimens. RESULTS: 76 inmates were included in 15 months and 21 were diagnosed with TB. The overall sensitivity, specificity, positive and negative predictive values of Xpert were respectively: 92.3%, 100%, 100% and 98.7% on raw sputum. The efficiency of the molecular POC was confirmed by a concordance of 97% between Xpert findings from the prison hospital and culture results. Delay of microbiological diagnosis was reduced by about 18 days for 13 inmates with smear-negative sputum that avoid the mobilization of major means (escort, transport) to perform fibroscopic samples. Repeated Xpert negative results helped to speed the lifting of inmate isolation. CONCLUSIONS: The implementation of Xpert in prison could optimize the management of incarcerated patients and thus limit the spread of TB among inmates, carers and other staff.

Prevalence of hepatitis E virus and reassessment of HIV and other hepatitis virus seroprevalences among French prison inmates.

BACKGROUND: Prison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population. METHODS: A prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution. RESULTS: In 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (p<0.0001) and was higher among Eastern Europe born inmates (p<0.0001). Between 2014 and 2017, HIV seroprevalence remained steady, while a decrease in HBV and HCV seroprevalence was observed. CONCLUSIONS: Compared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population.

Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery. METHODS AND FINDINGS: All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008). CONCLUSIONS: The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120367.

High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia.

BACKGROUND: The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia. METHODS: Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm. RESULTS: Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³ and the median viral load was 4.7 Log10. Second-line regimens prescribed were ddI/3TC/LPV/r (65.7%), ddI/TDF/LPV/r (10.0%), ddI/AZT/LPV/r (8.6%) and TDF/3TC/LPV/r (7.1%). The median CD4 T cell gain was +258 cells/mm³ at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis. CONCLUSIONS: These data suggest that a LPV/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.

Short communication: three years follow-up of first-line antiretroviral therapy in cambodia: negative impact of prior antiretroviral treatment.

There are few long-term data on ART-experienced patients in resource-limited settings. We performed a cross-sectional study of HIV-infected patients included in the ESTHER program in Calmette hospital, Phnom Penh, Cambodia, after 36 ± 3 months of cART. Therapeutic, clinical, and immunovirological outcomes were compared between patients who stated they were ART-naive (naive group), dual nucleoside reverse-transcriptase inhibitor (two-NRTI group), or fixed-dose combination of stavudine/lamivudine/nevirapine experienced (three-drug group) at entry to the program. A logistic regression model was used to evaluate the factors associated with virological failure (PCR HIV > 250 copies/ml). Among the 256 patients included in the analysis, 148 (58%) were ART naive while 50 (20%) had previously received two NRTIs and 58 (22%) three drugs. At entry to the program, all the patients received two NRTIs and one nonnucleoside reverse-transcriptase inhibitor (NNRTI). At evaluation, 46 patients (18%) were switched to a protease inhibitor-based regimen (9%, 32%, and 29% of the naive, two-NRTI, and three-drug groups; p < 0.0001). The median CD4 cell count increase was 180/µl overall (IQR: 96-276) and was higher in ART-naive than ART-experienced patients. In the intent-to-treat analysis, virological success was achieved in 83.5%, 67%, and 69% of the naive, two-NRTI, and three-drug groups, respectively (p = 0.002). Factors associated with virological failure were suboptimal previous ART exposure and WHO immunological failure criteria. The long-term efficacy of first-line cART is maintained in Cambodia. In ART-experienced patients, viral load monitoring needs to be available to establish early virological failure and preserve the potency of second line regimens.

Life-threatening interaction between antiretroviral therapy and vinblastine in HIV-associated multicentric Castleman's disease.

BACKGROUND: HIV-infected patients still present a high risk of developing lymphoproliferative malignancies, despite the fact that their prognosis has been considerably improved by highly active antiretroviral therapy (HAART). Potential interactions exist between antiretroviral drugs, in particular protease inhibitors, and anti-neoplastic ones, but their impact in terms of clinical and haematological adverse events remains unclear. METHODS: We report a case of potentially life-threatening interaction between vinblastine and antiretroviral therapy in a patient presenting with HIV-associated multicentric Castleman's disease (MCD). RESULTS: A 55-year-old HIV-1 infected patient was diagnosed with MCD while being treated with a salvage HAART regimen consisting of zidovudine, lamivudine, abacavir, nevirapine and ritonavir-boosted lopinavir. Vinblastine was prescribed as a monotherapy at the usual dose of 6 mg/m2 (i.e. 10 mg) every 3 weeks. The first vinblastine course was performed without HAART with no adverse event. Antiretroviral therapy was resumed for the two following courses which were associated with unexpected severe digestive and haematological toxicities, and moderate renal failure. Vinblastine was then administered alone at increasing doses without toxicity. HAART was finally resumed and we assessed that a decreased vinblastine dose of 2 mg/m2 was well tolerated, with a complete response of MCD. CONCLUSIONS: HAART regimen comprising protease inhibitors, which are potent inhibitors of cytochrome P450 and P-gp, could interfere with anti-neoplastic drugs, as demonstrated with vinblastine in our case report.