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Supplemental Digital Content is available in the text., Background: In an era of antibiotic resistance, modified dual therapy has been paid much attention because of simple drug composition and low resistance of amoxicillin. However, its eradication rate as a first-line regimen remains controversial. This study is to evaluate the efficacy and safety of modified dual therapy for the initial treatment of Helicobacter pylori (H. pylori) infection compared with mainstream first-line therapies. Methods: PubMed, the Cochrane Library, and Embase were searched for randomized clinical trials evaluating the efficacy and safety of modified dual therapy as the initial treatment for H. pylori eradication compared with guideline-recommended first-line therapies. A meta-analysis was conducted using Review Manager 5.3 and dichotomous data were estimated by the risk ratio (RR) with the 95% confidence interval (CI). We also performed subgroup analysis according to control groups and studies with antibiotic susceptibility tests. Results: Eight studies including 1672 patients with H. pylori infection met the selection criteria and were assessed. The meta-analysis demonstrated that modified dual therapy achieved similar efficacy [85.83% vs. 86.77%, RR 0.99 (95% CI, 0.95-1.03), intention-to-treat analysis; 89.53% vs. 90.45%, RR 0.99 (95% CI, 0.96-1.02), per-protocol analysis] and compliance [95.77% vs. 95.56%, RR 1.00 (95% CI, 0.98-1.02)] compared with recommended first-line regimens. In addition, there were no significant differences in comparing the eradication rate of modified dual therapy with clarithromycin triple therapy, bismuth quadruple therapy, and concomitant therapy, respectively. Subgroup analysis based on the studies with antibiotic susceptibility tests also confirmed a similar efficacy. However, modified dual therapy showed fewer adverse effects [8.70% vs. 22.38%, RR 0.39 (95% CI, 0.28-0.54)], with a significant difference (P

Background Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. Methods A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV = 5.93, and HRHLB = 2.84, p p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p p = 0.002), and subtype B′ infection (aOR = 8.22, p = 0.001). Conclusions In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B′ infection might also predict the occurrence of high-risk LLV.

Objective Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. Methods We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. Results We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR). Conclusions Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

Objectives Disruption in HIV care provision may enhance the development and spread of drug resistance due to inadequate antiretroviral therapy. This study thus determined the prevalence of HIV-1 transmitted drug resistance (TDR) in settings of decentralized therapy and care in Senegal and, the Ebola outbreak in Guinea. Antiretroviral-naïve patients were enrolled following a modified WHO TDR Threshold Survey method, implemented in Senegal (January–March 2015) and Guinea (August–September 2015). Plasma and dried blood spots specimens, respectively from Senegalese (n = 69) and Guinean (n = 50) patients, were collected for direct sequencing of HIV-1 pol genes. The Stanford Calibrated Population Resistance program v6.0 was used for Surveillance Drug Resistance Mutations (SDRMs). Results Genotyping was successful from 54/69 (78.2%) and 31/50 (62.0%) isolates. In Senegal, TDR prevalence was 0% (mean duration since HIV diagnosis 4.08 ± 3.53 years). In Guinea, two patients exhibited SDRMs M184V (NRTI), T215F (TAM) and, G190A (NNRTI), respectively. TDR prevalence at this second site, however, could not be ascertained because of low sample size. Phylogenetic inference confirmed CRF02_AG predominance in Senegal (62.96%) and Guinea (77.42%). TDR prevalence in Senegal remains extremely low suggesting improved control measures. Continuous surveillance in both settings is mandatory and, should be done closest to diagnosis/transmission time and with larger sample size.

Background Rilpivirine is safe and effective in HIV-naïve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine the reasons for prescribing the rilpivirine (RPV)/tenofovir disoproxil (TDF)/emtricitabine (FTC) co-formulation within the Swiss HIV Cohort Study and to assess its effectiveness and safety over a 24 months period. Methods All individuals enrolled in the Swiss HIV Cohort Study who initiated a RPV/TDF/FTC co-formulation between April 2013 and March 2014 were included. Primary outcomes were the HIV-RNA viral load (copies/mL) and CD4 cell count (cells/mm3) at 6, 12 and 24 months. Reasons for a switch to RPV/TDF/FTC were evaluated through a standardized questionnaire. We also assessed discontinuation and reasons for discontinuation of RPV/TDF/FTC until October 30, 2015. Results Of 644 individuals who started the RPV/TDF/FTC co-formulation, only 7.5% were treatment-naïve. At 24 months, viral suppression (HIV-RNA

Lung cancer is one of the most commonly encountered human malignancies. Due to the increase in life expectancy as well as the incidence of lung cancer, the incidence of senile lung cancer has increased significantly. We conducted a study to evaluate the efficacy and safety of gefitinib combined with γ-ray stereotactic body radiation therapy (SBRT) as the first-line treatment regimen for senile patients with adenocarcinoma of the lung. A total of 122 senile patients with adenocarcinoma of the lung were divided into 3 groups according to the treatment method. Group A included 35 patients treated with gefitinib combined with γ-ray SBRT, group B included 45 patients treated with γ-ray SBRT alone and group C included 42 patients treated with gefitinib alone. The patients received 250 mg of gefitinib per day, from the first day of the treatment until disease progression or discontinuation due to other causes. The patients were treated with γ-ray SBRT, initiated on the second day. The dose curve for this case group was 50–80%. The encircled dose was 4.0–6.5 Gy per fraction and the range of the total radiation dose was 36–48 Gy. The total number of treatments was 8–12, at a frequency of 5 times per week. All 122 patients were assessed by contrast-enhanced double helical computed tomography (CT) at 2 months. The tumor response rate (RR) of group A was 68.6% (24/35), the disease control rate (DCR) was 88.6% (31/35), the median overall survival (OS) was 15.5 months (range, 3–52 months) and the progression-free survival (PFS) was 7.8 months. The 1-year OS rate was 40.0% (14/35). The main side effects included skin rash and diarrhea. The RR of group B was 51.1% (23/45), the DCR was 71.1% (32/45), the OS was 9.6 months (range, 3–22 months) and the PFS was 5.3 months. The 1-year OS rate was 15.6% (7/45). The RR of group C was 40.5% (17/42), the DCR was 61.9% (26/42), the OS was 10.3 months (range, 3–26 months) and the PFS was 5.1 months. The 1-year OS rate was 35.7% (15/42). The main side effects included skin rash and diarrhea. The short-term therapeutic effect (RR) in group A was higher compared to that in group C (P=0.014, χ2=6.053); however, there was no significant difference compared to group B (P=0.116, χ2=2.477). The PFS of group A was higher compared with that of groups B and C (7.8 vs. 5.9, P=0.018 and 7.8 vs. 5.1, P=0.013, respectively). The OS of group A was higher compared with that of groups B and C (15.5 vs. 9.6, P=0.002 and 15.5 vs. 10.3, P=0.017, respectively). No significant differences were observed in PFS and OS between groups B and C. In conclusion, gefitinib combined with γ-ray SBRT appears to be feasible and effective as the first-line treatment in senile patients with adenocarcinoma of the lungs.

With ongoing earlier enrollment on and rapid scale-up of antiretroviral therapy (ART) in Cameroon, there are increasing risks of transmitted HIV drug resistance (HIVDR) at population levels. We, therefore, evaluated the threshold of HIVDR in a population initiating ART, to inform on the effectiveness of first-line regimens, considering HIV-1 diversity, plasma viral load (PVL), and CD4-based disease progression. A total of 53 adults [median (interquartile range, IQR) CD4: 162 cell/mm(3) (48-284); median (IQR) PVL: 5.34 log10 RNA (4.17-6.42) copies/ml] initiating ART in 2014 at the Yaounde Central Hospital were enrolled for HIV-1 protease-reverse transcriptase sequencing. Drug resistance mutations (DRMs) were interpreted using the 2009 World Health Organization (WHO) list versus the Stanford HIVdb algorithm version 7.0. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. Prevailing clade was CRF02_AG (71.70%). Based on Stanford HIVdb, a slightly higher proportion of patients with DRMs were found among ones infected with CRF02_AG than in those non-CRF02_AG infected (7.89% vs. 6.67%, p = 1.000), with lower PVL (7.69%

Objective This study aimed to assess the incidence and risk factors of treatment failure among HIV/AIDS-infected children who were on antiretroviral therapy (ART) in Amhara National Regional State, Ethiopia. Methods A retrospective follow-up study was conducted from January 2010 to March 2016. A total of 824 children under the age of 15 who had started ART were included in the study. Data were collected from children’s medical charts and ART registration logbook using a standard checklist. A Weibull regression model was used to identify the risk factors of treatment failure. Adjusted HRs (AHRs) with 95% CIs were used to declare statistical significance. Results The mean (±SD) age of the children was 6.4±3.6 years, with a median (IQR) follow-up of 30.5 (14.6–51.4) months. Sixty-three children (7.7%, 95% CI 5.8 to 9.5) developed treatment failure, 17 (27.0%) of whom were immunological and 46 (73.0%) were clinical failures. The incidence rate of treatment failure was 22.1/10 000 person-months. The cumulative probability of failure was 0.4, with 28 562.5 person-month observations. Lack of disclosure (AHR=4. 4, 95% CI 1.8 to 11.3), opportunistic infections during initiation of ART (AHR=2.3, 95% CI 1.3 to 4.1) and prolonged follow-up (AHR=0.06, 95% CI 0.02 to 0.18) were the main predictors of treatment failure. Conclusion This study revealed that the incidence of treatment failure remains a significant public health concern in Ethiopia. Undisclosed HIV status to children, the presence of opportunistic infections during initiation of ART and prolonged follow-up were found to be the main predictors of treatment failure. Hence, early detection of treatment failure and further studies on viral monitoring need to be considered.

Objectives To assess the prevalence of acquired drug resistance in HIV-1-infected patients living in Monrovia, Liberia, who had clinical and/or immunological failure of first-line ART according to WHO criteria. Patients and methods Patients receiving ART for >1 year with clinical and/or immunological failure were included. Sequencing of protease and reverse transcriptase regions was performed using Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) procedures and sequences were interpreted using the ANRS resistance algorithm. Results Ninety patients were enrolled. They had been receiving ART for a median time of 42 months and half were receiving zidovudine/lamivudine/nevirapine. Seventy-five per cent of patients were infected with CRF02_AG. Twenty-seven per cent of patients displayed a plasma viral load Conclusions The high prevalence of acquired drug resistance in patients followed in two centres of the Liberian capital city, documented after a median of 3 years on a first-line ART regimen, jeopardizes the activity of second-line regimens and highlights the need for virological monitoring in these settings.