HAART as a Strategy for Reduction of HIV-1 Transmission in Sub-Saharan Africa: Survival and Virus Load Parameters from the Drug Resource Enhancement against AIDS and Malnutrition Program

Background: The concept of universal antiretroviral use as a strategy for reduction of new cases of HIV infection has been evaluated in mathematical models as a potential approach to curtailing the Sub-Saharan African epidemic. In order to further substantiate such models, additional strategic parameters based on robust patient data should be considered, including survival of HIV-infected populations under HAART and subject infectivity as determined by HIV RNA levels. Methods: A retrospective cohort study was conducted in a population of patients enrolled in DREAMcenters throughout sub-Saharan Africa in order to determine survival under HAART. Cox regression analysis was performed evaluating parameters associated with survival such as CD4 cell count, viral load, body mass index (BMI) and hemoglobin (HB) levels. DREAM criteria for HAART initiation included (1) WHO stage 3-4 regardless of CD4 cell value (2) 100,000 copies in any subject. Virus load response to HAART was assessed in a subset of patients. Results: Adult non-pregnant patients who accessed DREAM centers from 1/2002 to 7/2009 were evaluated. A total of 34,295 patients (22,249 females/12,041 males) were included. Median age was 34 years (IQR:29-42) and median observation time 476 days (IQR:206 –950). Baseline median viral load, CD4 cell counts, HB and BMI values were 4.4 (IQR:3.6-5.0), 243 (IQR:109-416), 10.8 (IQR:9.2-12.4), and 20.3 (IQR:18.3-22.7).Over time 23,795 patients initiated HAART. Cox survival analysis (adjusted for Viral Load and HB) according to CD4 cell strata was performed. The relative risk of death in the lowest CD4 stratum (500) was 3.3 [2.7 –4.1]. Survival estimates at >7 years of HAART ranged from 50% to 95% according to baseline CD4 cell count and HB levels. In a subset of 13,405 subjects who received HAART for >6 months with at least 2 virus load measures available, 55.9% achieved < 50 copies/ml and an additional 19.7% achieved levels < 400 copies/ml (75.6% total). Final median virus load value was 58 (IQ: 0 –2000). Conclusions: Contrary to more conservative estimates used in mathematical modeling studies, patients in our cohort demonstrated a significant survival benefit even within the lowest CD4 cell stratum. Patients on HAART had low potential infectivity as measured by plasma virus load. Cohort data from African patients can contribute to the further refinement of predictive models

An assessment of option B implementation for the prevention of mother to child transmission in Dschang, Cameroon: results from the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) cohort

Introduction: Scaling up of antiretroviral therapy (ART) to HIV+ pregnant women is crucial for the elimination of HIV infection in children. The aim of this study was to evaluate the feasibility and effectiveness of triple ART for Prevention of Mother-to Child Transmission (PMTCT) in Cameroon. Methods: HIV-positive pregnant women attending the DREAM Centre of Dschang, Cameroon for prenatal care were enrolled in a prospective cohort study, and received ART until the end of breastfeeding or indefinitely if their CD4 count was &lt;350mm3. Infants were evaluated for HIV infection at 1, 6 and 12 months of age. Results: A total of 298 women were enrolled. Among them, 152 were already on established ART. Women were followed until 6 months after delivery with a retention rate of 92.6%. Eight women died. Those with a CD4 count &lt;350 cells/mm3 during pregnancy had the highest mortality risk (RR 2.53; 95% CL= 1.86-3.44). The HIV  transmission rate was 1.2% at 12 months with an HIV free survival of 91%. In the proportional Cox regression analysis, the following factors were positively associated with infant mortality: maternal CD4&lt; 350 cells/mm3, no breastfeeding in the first 6 months of life, weight-for-age z score &lt; -2. Conclusion: Results confirm the feasibility and effectiveness of the implementation of Option B, with very low rates of HIV MTC  transmission, and potential benefits to the health of mothers and infants with earlier initiation of ART. Breastfeeding again demonstrates to be highly beneficial for the growth and survival of HIV exposed children.Pan African Medical Journal 2016; 2

Intermediate care units in progressive patient care model: a systematic literature review

Background: Progressive patient care (PPC) has been defined as a systematic classification and segregation of patients based on their medical and nursing needs. Aim of the present research was to perform a systematic literature review about existing medical intermediate care unit organizational models and their performance strengths and weaknesses with a specific focus on Italian implementation, respect to US model. Methods: Databases PubMed, Cinahl, Google and Google Scholar were searched until September 2017. The search was limited to Italian and English studies. All study design are included in the review. Results: Ten studies were included in the review. The American studies showed, after the PPC reorganization, an increase in level of satisfaction and nursing care, a reduction in average length of stay, costs and tensions between nurses and an improvement in nurse-physician communication. An Italian study reported the results of a project carried out in three case studies (Forlì, Foligno and Pontedera hospital), redesigning hospital patient flow logistics around the concept of intensity of care: in all three cases, after the reorganization, an increase in bed occupancy rate (before: 71%,81%,65%; after: 78%,84%,82%, respectively) and in hospital case-mix complexity (average DRG weight - before: 0.99,1.07,1.12; after: 1.19,1.09,1.61, respectively) and a reduction in turn-over ratio (before: 2.5,1.4,2.8; after: 1.5,1.2,1.7, respectively) was recorded. Considering Italian healthcare professionals’ point of view, majority of internists supported a hospital remodeling according to PPC model. Conclusions: The PPC model, theorized in US, has found several applications in Italian regional realities. Improvements in quality of care, appropriateness and productivity in healthcare facilities, that adopted the PPC program, were observed

Measurement of viral load by the automated Abbott real-time HIV-1 assay using dried blood spots collected and processed in Malawi and Mozambique

Background. The use of dried blood spots (DBS) for HIV-1 viral load quantification can greatly improve access to viral monitoring for HIV-infected patients receiving treatment in resource-limited settings.Objectives. To evaluate and validate HIV viral load measurement from DBS in sub-Saharan Africa, with a reliable, all-automated, standard commercial assay such as the Abbott m2000.Methods. A total of 277 DBS were collected in different health centres in Malawi and Mozambique and analysed for viral load determination using the Abbott m2000 assay with the corresponding plasma samples as gold standard. Samples were extracted using the m2000SP automatic extractor and then processed as the plasma samples using the specific 1.0 mL HIV-RNA DBS protocol.Results. Among samples with detectable HIV-RNA the correlation between viral load obtained from the paired 131 plasma and DBS samples was high (r=0.946). Overall, viral load values between DBS and plasma differed by less than 0.5 log unit in 90.1% of cases and by less than 1 log unit in 100% of cases. Using a threshold of 1 000 copies/mL (defining virological failure in resource-limited settings), sensitivity was 94.2% and specificity 98.6%, and both positive and negative predictive values were high (98.5% and 94.5%, respectively).Conclusion. DBS extracted and processed using the Abbott automated system can be reliably used in resource-limited setting to diagnose virological failure

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: Implications for the activity of next-line regimens from a longitudinal study in Mozambique

Background: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC). Methods and results: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/μl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL. Conclusions: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

LHCb upgrade software and computing : technical design report

This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages