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Background We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study. Methods Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m2, and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis). Results At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4+ cell count (<200 cells/mm3; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1–2); no serious drug-related AEs occurred. Conclusions Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting. [ABSTRACT FROM AUTHOR]

HIV-infected children are now living into adolescence and early adulthood in large numbers due to the availability and increased use of antiretroviral therapy (ART). However, receipt of HIV status disclosure among children remains low. We assessed the association between disclosure of HIV status and adherence to ART among children in the Masaka region of Uganda using multivariable logistic regression with generalised linear models with Poisson log-link function and robust variance in Stata software version 15.1. Data were collected from 524 assenting children aged 12–17 years between March and December 2020. Results show that, although not statistically significant, children who received disclosure of their HIV status reported improved ART adherence compared to children with no disclosure. Out-of-school children with post-primary education and children on first-line ART regimens were significantly more likely to report improved ART in both crude and adjusted analyses. Innovative interventions to promote progressive disclosure of HIV status to children on ART, in school, are needed to improve their ART adherence. There is also a need to evaluate the suitability of current counselling interventions provided to children being switched to second-line ART regimens to delay the need for third-line ART regimens. [ABSTRACT FROM AUTHOR]

Abstract 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

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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 <  0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, 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 <  0.001) or DDI-based regimen (aOR = 9.96, 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. [ABSTRACT FROM AUTHOR]

Abstract 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

Purpose: S-1 plus cisplatin therapy is the recommended standard first-line regimen for human epidermal growth factor receptor 2 (HER-2)-negative advanced unresectable or recurrent gastric cancer (AGC) in the Japanese Gastric Cancer Treatment Guidelines. By contrast, capecitabine plus cisplatin (XP) therapy has been second-line therapy for these patients. This prospective study aimed to evaluate the efficacy and safety of XP as a first-line regimen for HER2-negative patients with AGC.Methods: In this multicenter, open-label, phase II study, patients received cisplatin (80 mg/m2 i.v. day 1) plus capecitabine (1000 mg/m2 orally, twice daily, days 1-14) at 3 week intervals until disease progression or non-continuation for various reasons. The primary endpoint was overall response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profiles.Results: Thirty-six patients with HER2-negative AGC were enrolled in this study. Of these, 16 patients with evaluable lesions were assessable for efficacy and 36 were assessable for toxicity. One patient achieved a complete response and five partial responses. The overall response rate was 37.5% [95% confidence interval (CI) 13.7-61.2%] calculated on an intention-to-treat basis. The median PFS and median OS were 5.2 months (95% CI 4.2-6.2 months) and 16.9 months (95% CI 5.8-27.9 months), respectively. Treatment-related adverse events were generally mild; the most common grade 3/4 adverse event was neutropenia (27.8%), followed by anorexia (19.4%), leucopenia (16.7%), anemia (16.7%), and nausea (13.9%).Conclusion: XP as first-line therapy is effective and well tolerated by patients with HER2-negative AGC. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) incidence rates are rapidly increasing in developed countries, with half the patients being metastatic at diagnosis. For decades, fluorouracil, then gemcitabine regimens were the preferred palliative first-line options for fit patients with metastatic PC. FOLFIRINOX (a combination of bolus and infusional fluorouracil, leucovorin, irinotecan and oxaliplatin) was introduced to clinical practice in 2010 due to the results of the phase II/III trial (PRODIGE 4/ACCORD 11) comparing FOLFIRINOX with single-agent gemcitabine as first-line treatment for patients with MPC. Median overall survival, progression-free survival, and objective response rate were superior with FOLFIRINOX over gemcitabine and there was prolonged time to definitive deterioration in quality of life. Although FOLFIRINOX was also associated with increased toxicity, mainly febrile neutropenia and diarrhea, there has been rapid uptake of this regimen. This review closely examines optimal management and prevention of toxicities, international recommendations for first-line treatment, and use of modified FOLFIRINOX protocols. In this review, we also look at the potential benefit of FOLFIRINOX in selected groups of patients: second-line therapy, adjuvant chemotherapy, induction therapy in patients with borderline resectable and locally advanced PC. Robust validation of the FOLFIRINOX regimen in these settings requires confirmation in further randomized trials. [ABSTRACT FROM AUTHOR]

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 <50 copies/mL) was achieved in 100% and 96.7% of cART-naïve and cART-experienced patients respectively. The switch to RPV was mainly done for simplification (44.6%) and to overcome central nervous system toxicity symptoms due to efavirenz (24%). Six months after switch, 74.8% of patients reported an improvement of psycho-neurological symptoms with continued improvement at 12 months for almost 80%. However, one quarter of patients reported a discontinuation of RPV/TDF/FTC on October 30, 2015 after a median time of 18.4 months. Reasons for discontinuation included physician decision (5.3%) and side-effects (3.9%) mainly related to the central nervous system and to renal toxicity.Conclusion: The RPV/TDF/FTC co-formulation was safe and effective throughout 24 months of follow-up but barely prescribed for HIV-naïve patients. Despite excellent virological suppression among both treatment-naïve and -experienced patients, we observed a high rate of treatment discontinuation. [ABSTRACT FROM AUTHOR]

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 ,50 copies/mL. Among the 66 patients with detectable viraemia, the median viral load was 4.7 log10 copies/mL (IQR=3.0-5.6). The prevalence of NRTI and NNRTI resistance-associated mutations (RAMs) was 63% and 71%, respectively; and the median number of NRTI and NNRTI RAMs was 2 and 3, respectively. Two patients (4%) displayed viruses with PI RAMs. Regarding NRTI drug resistance, 29%, 38%, 63%, 29% and 25% of patients had viruses resistant to zidovudine, stavudine, lamivudine/emtricitabine, abacavir and tenofovir, respectively. Regarding the NNRTI drug class, 56%, 65%, 33% and 42% of patients had viruses resistant to efavirenz, nevirapine, etravirine and rilpivirine, respectively. 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 ARTregimen, jeopardizes the activity of secondline regimens and highlights the need for virological monitoring in these settings. [ABSTRACT FROM AUTHOR]

Objectives Viral load ( VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief ( PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. Methods In this cross-sectional, observational study, patients on first-line antiretroviral therapy ( ART) (efavirenz or nevirapine + zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load ( HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or > 24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. Results We found that 85.2% of 325 subjects were virologically suppressed (viral load < 47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P < 0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio ( OR) 0.47; 95% confidence interval ( CI) 0.22-1.02; P = 0.057], lower cost of clinic visits ( OR 0.815; 95% CI 0.66-1.00; P = 0.05), improvement in CD4 percentage ( OR 1.06; 95% CI 1.014-1.107; P = 0.009), and care at Kayunga vs. Kangulamira ( OR 0.47; 95% CI 0.23-0.92; P = 0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy ( ART) ( P < 0.0001), patient satisfaction with care ( P = 0.038), improvements in total lymphocyte count ( P < 0.0001) and haemoglobin concentration ( P = 0.05) were positively associated, whereas age at start of ART ( P = 0.0045) was negatively associated with this outcome. Conclusions High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor ( NNRTI) administered with zidovudine ( ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non- TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non- TA group). Methods Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non- TA. Results A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non- TA. No significant differences were observed between the non- TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors ( RTIs) occurred at a significant lower frequency in the non- TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor ( NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non- TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non- TA group (18.5%; P < 0.001). Conclusions At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non- TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This phase II trial aimed to evaluate feasibility and efficacy of a first-line combination of targeted therapies for advanced non-squamous NSCLC: bevacizumab (B) and erlotinib (E), followed by platinum-based CT at disease progression (PD). Methods: 103 patients with advanced non-squamous NSCLC were treated with B (15mg/kg day 1 of each 21-day cycle) and E (150mg daily) until PD or unacceptable toxicity. Upon PD patients received 6 cycles of CT (cisplatin/carboplatin and gemcitabine). The primary endpoint was disease stabilization rate (DSR) after 12 weeks of BE treatment. Results: 101 patients were evaluable. Under BE, DSR at week 12 was 54.5%. 73 patients had at least stable disease (SD), including 1 complete remission and 17 partial responses (PR). No unexpected toxicities were observed. Median time to progression (TTP) under BE was 4.1 months. 62 patients started CT; 35 received at least 4 cycles (6 PR, 32 SD). At a median follow-up of 36 months, median overall survival (OS) was 14.1 months. Conclusions: First-line BE treatment followed by a fixed CT regimen at PD is feasible with acceptable toxicity and activity. In a non-squamous NSCLC population unselected for EGFR status, we found OS rates similar to standard CT. [Copyright &y& Elsevier]

Although used globally, little data exist on the efficacy of nevirapine (NVP) used in combination with tenofovir (TDF)/emtricitabine or lamivudine (XTC), and no large randomized prospective control trials exists comparing this combination with efavirenz (EFV)/TDF/(XTC).As part of the AIDSRelief program, a retrospective review of patient medical chart information along with a cross-sectional viral load, and adherence measurement was conducted between 2004 and 2009. An on-treatment analysis excluded patients who died, transferred out of care, or were lost to follow-up. A switch of antiretrovirals for any reason was considered a failure in the intent-to-treat analysis. Patients with only clinically relevant reasons for switching such as toxicity, adverse effects, viral failure or clinical/immunological failure, lost to follow-up, and death were considered failures as part of the modified-intent-to-treat analysis. Step-wise multiple regression analysis was used to identify variables that were associated with viral suppression.A random sample of 3862 patients met criteria and were included in this analysis. In the on-treatment analysis, older age (P < 0.004) and baseline CD4 <100 cells per cubic millimeter (P < 0.021) were the most significant variables impacting viral load. Patients on TDF/XTC/EFV achieved higher rates of viral suppression compared with patients on TDF/XTC/NVP or azidothymidine (AZT)/lamivudine (3TC)/NVP.Our data show that patients on TDF/XTC/EFV had better outcomes than patients on TDF/XTC/NVP, AZT/3TC/EFV, or AZT/3TC/NVP. High rates of virologic suppression seen in patients on this regimen are consistent with previous studies and indicate the need to increase use of this regimen in HIV programs to promote sustainable viral suppression over time. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the efficacy and safety of gefitinib combined with γ-ray stereotactic radiotherapy for senile patients with adenocarcinoma of lung as the first-line regimen. Methods: The 153 senile patients with adenocarcinoma of lung were divided into 4 groups according to the therapy method. Group A was the 35 patients treated with gefitinib combined with γ-ray stereotactic radiotherapy. Group B was the 45 patients treated with γ-ray stereotactic radiotherapy. Group C was the 42 patients treated with gefitinib. Group D was the 31 patients treated with best supportive therapy. The patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients were treated with γ-ray stereotactic radiotherapy from the second day. Dose curve of this group of cases was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 36-48 Gy. The total number of treatment was 8-12 and treated six times every week. Results: All the patients were examined by enhanced double helix CT at the second month. The tumor response rate (RR) of group A was 68.6% (24/35). Disease control rate (DCR) was 88.6% (31/35). The median survival time (MST) was 13.4 months (range 3-34 months) and the progression-free survival (PFS) was 7.8 months. The overall 1-year survival 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). DCR was 71.1% (32/45). MST was 9.6 months (range, 3-18 months) and PFS was 5.3 months. The overall 1-year survival rate was 15.6 % (7/45). The RR of group C was 40.5 % (17/42). DCR was 61.9% (26 /42). MST was 10.3 months (range, 3-26 months) and PFS was 5.1 months. The overall 1-year survival rate was 35.7 % (15/42). The main side effects included skin rash and diarrhea. The MST of group D was 5.6 months (range, 2-11 months) and PFS was 1.7 months. The overall 1-year survival rate was 0. The short-term therapeutic effects (RR) of group A was higher than group C ( P = 0.014 < 0.05, χ = 6.053) but has no significant difference with group B ( P = 0.116 > 0.05, χ = 2.477). The long-term therapeutic effects (overall 1-year survival rate) of group A was higher than group B ( P = 0.014 < 0.05, χ = 6.077) but has no significant difference with group C ( P = 0.642 > 0.05, χ = 0.216). Conclusion: Gefitinib combined with γ-ray stereotactic radiotherapy is feasible and effective for treatment in senile patients with adenocarcinoma of lung as the first-line regimen. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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, χ 2 =6.053); however, there was no significant difference compared to group B (P=0.116, χ 2 =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.