bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morbidity and mortality in HIV‐exposed under‐five children in a rural Malawi setting: a cohort study
Authors: Divala Oscar , Michelo Charles , Ngwira Bagrey 
Published: November 2014

IntroductionPaediatric HIV infection significantly contributes to child morbidity and mortality in southern Africa. In Malawi as in most countries in the region, care of HIV‐exposed children is constrained by the lack of area‐specific information on their risk to dying and morbidity. This research estimates and compares morbidity and mortality events between HIV‐exposed and ‐unexposed under‐five children in a rural Malawian setting.MethodsData for children under the age of five collected from January 2009 to June 2011 at a demographic and health site in Karonga district of northern Malawi were analyzed. Morbidity and mortality rates among HIV‐exposed and ‐unexposed children were calculated and compared using Kaplan‐Meier survival analysis and Cox proportional hazard regression.ResultsOverall (n=7,929) cohort data of under‐five children born in a demographic and health site represented 12380.8 person years of observation (PYO) of which 3.1% were contributed by HIV‐exposed infants. Females accounted for half of the sample, and the overall mean age was 18.4 months (SD 13.4) with older children in the HIV–unexposed group. All‐cause morbidity rate was 337.6/1000 PYO (95% CI 327.5/1000–348.0/1000) and HIV‐exposed children morbidity rate was 1.34 times higher (p<0.001) compared to HIV‐unexposed children. integrated management of childhood illness (IMCI) pneumonia was the most common diagnosis (39.3%) in this cohort. Child mortality rate was 16.6/1000 PYO (95% CI 14.5–19.1) from 206 deaths. HIV‐exposed children had 4.5 times higher (p<0.001) mortality rate compared to the HIV‐unexposed children. Higher mortality rates were observed in children under one year (129.2/1000 PYO) compared to older age groups.ConclusionHIV exposure at birth has a greater impact on child morbidity and mortality especially in the first year of life. This underscores the need for targeted and synergetic interventions that included focused prevention of mother‐to‐child transmission (PMTCT) which could reduce HIV transmission to children in their infancy in this setting.
The spectrum of HIV mother‐to‐child transmission risk
Authors: Reliquet Veronique , Winer Norbert , Chereau Natacha , Launay Elise , Lamberet Aurore , Andre‐Garnier Elisabeth , Raffi Francois , Brunet Cecile 
Published: November 2014

IntroductionWith the implementation of combined antiretroviral therapy (cART) and prevention of mother‐to‐child transmission (MTCT) we observed dramatic decreases in rates of perinatal MTCT of HIV, 0.3% in France in women with plasma viral load (pVL) <50 c/mL at delivery. We describe a case of MTCT which occurred despite virologic suppression of the mother at delivery, the first case in our centre since 2002.Description of the caseA 26‐year‐old black woman, Guinea‐native, living in France since 2007, was diagnosed with HIV‐1 CRF02 in 2008 and lost to follow‐up since November 2012 after second delivery (2 female born in March 2009 and October 2012, uninfected). Third pregnancy began in July 2013 and baseline characteristics in September were as follows: week 13 of gestational age (GA), CDC stage A, CD4 317/mm3, pVL 4.89 log c/mL. cART with abacavir/lamivudine and atazanavir/ritonavir 300/100 mg daily (qd) was introduced. VL decreased to 2.4 log c/mL in 4 weeks and CD4 increased to 456/mm3. In December, at week 22 of GA, viral rebound at 4.14 log c/mL due to sub‐optimal maternal adherence was observed. After counselling, pVL decreased to 1.69 log c/mL in March 2014, at week 35 of GA and 1.3 log c/mL at delivery. As pVL was <400 c/mL at week 36 of GA, vaginal delivery with IV zidovudine was decided. However, because of poor/uncertain maternal adherence to cART, the neonate was treated with a combination of 2 drugs (lamivudine‐nevirapine) with the 4‐week zidovudine regimen, until the result of delivery pVL. This combination was stopped at day 2 when maternal delivery pVL (22 c/mL) was received and standard oral zidovudine prophylaxis was continued. Infant was tested for HIV infection at baseline (day 3) and found to be HIV‐infected (HIV‐RNA 60 c/mL) attesting in‐utero HIV transmission. On day 15, zidovudine prophylaxis was discontinued and treatment for HIV infection initiated with standard cART according to the French Paediatric Antiretroviral Guidelines.ConclusionsThe risk of HIV acquisition is low in infants born to women who receive standard cART during pregnancy and labour and achieve undetectable VL at delivery. However, transmission remains a hazard, with possibility of in‐utero infection during episodes of non‐adherence, and the risk of a possible MTCT has to be mentioned to all pregnant women.
Overall and cause‐specific mortality in HIV‐positive subjects compared to the general population
Authors: Alejos Belen , Hernando Victoria , López‐Aldeguer Jose , Segura Ferrán , Antonio Oteo José , Rubio Rafael , Sanvisens Arantza , Sobrino Paz , del Amo Julia , Coris Cohort 
Published: November 2014

IntroductionEmerging non‐AIDS related causes of death have been observed in HIV‐positive subjects in industrialized countries. We aimed to analyze overall and cause‐specific excess of mortality of HIV‐positive patients compared to the general population and to assess the effect of prognostic factors.Material and MethodsWe used generalized linear models with Poisson error structure to estimate overall and cause‐specific excess of mortality in HIV‐positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short‐term and long‐term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data.ResultsIn 9162 patients there were 363 deaths, 16.0% were non‐AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all‐cause mortality, 0.16 for liver, 0.10 for non‐AIDS malignancies and 0.03 for cardiovascular. Short‐term (first‐year follow‐up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06–6.01) and 1.47 (95% CI 0.95–2.27) for HCV coinfection; long‐term (subsequent follow‐up) eHR for baseline AIDS was 0.88 (95% CI 0.58–1.35) and 4.48 (95% CI 2.71–7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21–34.84) and in HCV‐coinfected patients (eHR: 3.85, 95% CI 0.85– 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4–12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6–13) showed a higher risk of non‐AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25–35.73).ConclusionsOur results show overall, liver, non‐AIDS malignancies and cardiovascular excess of mortality associated with being HIV‐positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short‐term and long‐term effect of AIDS before entry and HCV coinfection was found for overall mortality.
Burden of subclinical heart and lung disease detected on thoracic CT scans of HIV patients on HAART
Authors: Zona Stefano , Santoro Antonella , Besutti Giulia , Ligabue Guido , Mussini Cristina , Raggi Paolo , Leipsic Jonathon , Sin Don D. , Guaraldi Giovanni 
Published: November 2014

IntroductionThe aim was to determine the prevalence of lung and heart abnormalities on thoracic CT scans in HIV‐infected patients who were treated with antiretroviral therapy (ART).Material and MethodsThoracic CT scans of 903 patients infected with HIV (mean age 48±7 yrs, 29% females) were reviewed by three radiologists by consensus. Patients were phenotyped according to smoking status, pack years and years since cessation for ex‐smokers. Individuals known to have active lung or heart disease at the time of CT scanning were excluded. Multimorbidity lung and heart disease (MLHD) was defined by the presence of >2 lung or heart abnormalities on the CT scan.ResultsPrevalence of lung abnormalities were: 326 patients (36.1%) with emphysema, 271 (30.0%) with bronchiolitis, 44 (4.9%) with non‐calcified lung nodules, 568 (63%) with significant bronchial wall thickening, 150 (16.7%) with bronchiectasis, 9 (1%) with interstitial lung disease. Overall, 445 patients (49.3%) had >2 lung abnormalities. Imaging findings suggestive of prior myocardial infarction (MI) were found in 1.4% (13 patients); 26.6% (240 patients) had CAC scores of 1 to 100, and 9.8% (89 patients) had CAC>100. 13.6% (123 patients) of the patients had CAC>100 and/or previous MI. MLHD was present in 484 patients (53.6%) and among 78 patients (16%) who never smoked. Table 1 describes CT findings according to pack year and stop smoking groups vs never smokers.MLHD increased proportional to cumulative smoking history (p for trend <0.001) and decreased in proportion to the number of years since smoking cessation (p for trend=0.017). Independent predictors for MLHD were: age (OR=1.07, CI 1.05–1.10), sex (OR=1.59, CI 1.15–2.19), current smoking (OR=1.76, CI 1.08–2.89), and pack‐years history of smoking (OR=1.03, CI 1.02–1.05). In patients who never smoked, nadir CD4<200 was significantly associated with MLHD after adjustment for age and sex (OR=1.98, CI 1.98–3.63).ConclusionsMLHD is common in HIV‐infected individuals even in non‐smokers. Reduced CD4 count (hence severity of HIV infection) may be an important risk factor for chronic lung and heart disease. Thoracic CT scans may provide an excellent screening tool to detect MLHD in HIV‐infected patients.
Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV‐1 positive patients in Turkey
Authors: Sayan Murat , Sargýn Fatma , Inan Dilara , Yýldýz Sevgi Dilek , Kocagül Celikbas Aysel , Yasar Kadriye , Kaptan Figen , Sayýn Kutlu Selda , Tasdelen Fýsgýn Nuriye , Inci Ayse , Ceran Nurgül , Karaoðlan Ýlkay , Cagatay Atahan , Kemal Celen Mustafa , Tekin Koruk Suda , Ceylan Bahadýr , Yýldýrmak Taner , Akalýn Halis , Korten Volkan , Willke Ayse 
Published: November 2014

IntroductionThe objective of this study was to determine the transmitted drug resistance mutations (TDRMs) in newly diagnosed HIV‐1 positive patients in Turkey.Materials and MethodsThe study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV‐1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%) male, median age: 37 (range; 1–77), median CD4+T‐cell: 360 (range; 1–1320) count/mm3, median HIV‐RNA load: 2.10+E6 (range; 4.2+E2–7.41+E8) IU/mL. HIV‐1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41–238) and protease (codon 1–99) domains of pol gene of HIV‐1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1].ResultsThe patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi‐class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV‐1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3% (34/774), respectively.ConclusionsThe TDRMs prevalence of antiretroviral naïve HIV‐1 infected patients may be suggested current situation of Turkey. These long‐term and large‐scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey.
Long‐term efficacy and safety of E/C/F/TDF vs EFV/FTC/TDF and ATV+RTV+FTC/TDF in HIV‐1‐infected treatment‐naïve subjects ≥50 years
Authors: Gazzard Brian , Marie Girard Pierre , Di Perri Giovanni , Gallant Joel , Towner William , Rogatto Felipe , Demorin Jennifer , McColl Damian , Liu Hui , Rhee Martin , Szwarcberg Javier , Piontkowsky David 
Published: November 2014

IntroductionIn high‐income countries, ≥30% of HIV‐infected patients are ≥50 years (yrs) old (UNAIDS 2013). In two phases, three clinical trials (Studies 102 and 103) elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; STB) had non‐inferior efficacy and favourable safety vs efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF; ATR) or ritonavir‐boosted atazanavir (ATV+RTV)+FTC/TDF (TVD) in HIV‐infected, treatment‐naïve subjects at Week 144. The efficacy and safety of STB in subjects < or ≥50 yrs is described.Materials and MethodsPost hoc analysis of efficacy, tolerability and safety in subjects < or ≥50 yrs at Week 144.ResultsSubjects ≥50 yrs in Study 102: STB: 14% (49/348), ATR: 16% (56/352); in Study 103: STB: 14% (48/353), ATV+RTV+TVD: 14% (48/355). Efficacy, safety and tolerability by age and study endpoint are shown in Table 1. Regardless of age, STB had robust efficacy at Week 144 with similar virologic outcomes vs ATR or ATV+RTV+TVD. Discontinuations (DC) due to AE on STB were similar to the comparators, most occurred by Week 48. Median changes in eGFR on STB were similar by age; DC with renal PRT was rare [STB: 4 (0.6%); ATV: 3 (0.8%); ATR: 0], 2 and 1 in ≥50 yrs old strata, respectively.ConclusionsSTB compared to ATR or ATV+RTV+TVD, is an efficacious, well‐tolerated and safe regimen for HIV‐1‐infected, treatment‐naïve subjects<or≥50 yrs of age.
An observational comparison of first‐line combination antiretroviral treatment (cART) with 2NRTI and ATV/r or DRV/r in HIV‐infected patients in Italy
Authors: Cozzi‐Lepri Alessandro , Antinori Andrea , Bonora Stefano , Cingolani Antonella , Cassola Giovanni , Angarano Gioacchino , Vullo Vincenzo , Mussini Cristina , Gori Andrea , Maggiolo Franco , Castagna Antonella ,   Antonella d'Arminio Monforte on behalf of the ICONA Foundation Study
Published: November 2014

IntroductionIn a recent clinical trial (ACTG 5257), no difference in viral failure (VF) of a first‐line cART containing atazanavir/r (ATV/r) or darunavir/r (DRV/r) was found [1]. For the endpoint of discontinuation due to intolerance, the regimen with DRV/r was superior to that of ATV/r (49% of the stops of ATV/r were attributed to jaundice or hyperbilirubinemia). These and other intolerances to ATV/r remain a concern for clinicians.MethodsParticipants in the ICONA Foundation Study who started cART with 2NRTI+ ATV/r or DRV/r while ART‐naïve were included. Several endpoints were evaluated: confirmed VF>200 copies/mL after six months of therapy, discontinuation of DRV/r or ATV/r for any reasons or because of intolerance/toxicity (as reported by the treating physician) and the combined endpoint of VF or stop. Survival analysis with Kaplan–Meier curves and Cox regression model stratified by clinical site was used. Patients' follow‐up accrued from cART initiation to the date of the event or to the date of last available visit/viral load.Results894 patients starting 2NRTI+ATV/r and 686 2NRTI+DRV/r when ART‐naïve on average in 2011 (IQR: 2010–2012) were studied. Most common NRTIs used were FTC/TDF (84%) and ABC/3TC (12%). Median age was 40 years, 22% females, 44% heterosexuals. Patients starting ATV/r were more likely to be hepatitis B/C infected (2% and 14% vs 1% and 9%, p=0.001), they started one year earlier (2011 vs 2012, p=0.001), were more likely to be enrolled in sites located in the north of Italy (63% vs 54%, p=0.04), started cART less promptly after HIV diagnosis (5 vs 2 months, p=0.02) and less likely to have started TDF/FTC (83% vs 85%, p=0.02). By two years of cART, 9.8% (95% CI 7.6–12.0) of those starting ATV/r experienced discontinuation due to intolerance/toxicity vs 6.5% in DRV/r group (95% CI 4.2–8.8, p=0.04). After controlling for several potential confounders (age, gender, nation of birth, mode of HIV transmission, hepatitis co‐infection status, AIDS diagnosis, nucleoside pair started, baseline CD4 count and viral load and year of starting cART) the relative hazard (RH) for ATV/r vs DRV/r was 2.01 (95% CI 1.23, 3.28, p=0.005). There were no statistical differences detected for any of the other outcomes.ConclusionsAlthough unmeasured confounding cannot be ruled out, our results seem to be consistent with those of the ACTG 5257. When all cause discontinuations were considered, or the composite endpoint of treatment failure, there was no difference between ATV/r‐ and DRV/r‐based regimens.
Long term effectiveness of once‐daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression
Authors: Llibre Josep M , Cozzi‐Lepri Alessandro , Antonio Valencia La Rosa Jorge , Pedersen Court , Ristola Matti , Losso Marcelo , Mocroft Amanda , Mitsura Victor M. , Ormaasen Vidar , Maltez Fernando , Beniowski Marek , Paredes Roger ,   on behalf of Eurosida in Eurocoord
Published: November 2014

BackgroundUse of unboosted atazanavir (ATV400) is approved in the US but not in Europe [1]. Due to pharmacokinetic interactions it should not be used with tenofovir but can be used with abacavir/lamivudine (ABC/3TC) [1, 2,3]. Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant.MethodsWe evaluated treatment outcomes of ATV400+ABC/3TC in pre‐treated subjects in the EuroSIDA cohort with undetectable HIV‐1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV‐1 RNA >50 c/mL.ResultsWe included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co‐infection 36%, median baseline CD4 at switch 540 cells (360, 700), time with VL≤ 50 c/mL 45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010). The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25 (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV‐RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis virus co‐infection, CD4 count at time of switching or third drug used in the previous regimen.ConclusionsA switch to ATV400+ABC/3TC in selected subjects with HIV‐RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long‐term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.
Bone mineral density improvement after 48 weeks of switch to maraviroc+darunavir/ritonavir 300/800/100 mg QD, preliminary results of GUSTA study
Authors: Bianco Claudia , Rossetti Barbara , Gagliardini Roberta , Lamonica Silvia , Fanti Luri , Lombardi Francesca , Cauda Roberto , Di Giambenedetto Simona , De Luca Andrea 
Published: November 2014

IntroductionLow bone mineral density (BMD) and osteoporosis are prevalent in HIV‐infected patients and were associated with HIV infection and tenofovir‐containing ART.Materials and MethodsThe GUSTA study (GUided Simplification with Tropism Assay) is a two‐arm, prospective, multicenter, 1:1 randomized controlled trial designed to demonstrate the non‐inferiority of therapeutic switch to maraviroc+darunavir/ritonavir (MVC+DRV/r) 300/800/100 mg QD against the continuation of previous triple cART in patients with stable virological suppression. Enrolment criteria include HIV1‐RNA <50 copies/mL for >6 months, R5 tropism and CD4>200 cells/µL for >3 months. Dual energy X‐ray absorptiometry scans of proximal femur and lumbar spine were performed at baseline and week 48. Bone composition was evaluated using L2‐L4 lumbar column and proximal femoral BMD, T‐score and the Z‐score. At the same timepoints, plasma bone metabolism biomarkers were measured. Linear regression was used to compare means of differences between arms. The association between BMD changes and the baseline variables was assessed by linear regression.Results27 patients were included, 13 from study group and 14 from control group, 74.1% were males, 44.4% heterosexuals, 81.5% Caucasian, median age was 47 years (IQR 41–53), time from HIV diagnosis 13.4 years (9–19), CD4 553/µL (406–739), nadir CD4 201/µL (76–283). At baseline, median ART duration was 10.5 years (5.7–15.3), the majority of patients (70.4%) was on tenofovir, 63% was on a PI‐based regimen and 14,8% on an NNRTI‐based regimen. Mean proximal femur BMD from baseline increased over 48 weeks by 2.06% (SD 2.24) in the study arm and decreased by −2.77% (SD 4.63) in control arm (p=0.003). The change over 48 weeks in proximal femur T‐score was significantly different between the study (+0.11, SD 0.22) and control arm (−1.14, SD 0.27, p=0.016). Also the changes in total alkalin phosphatase (−20 U/L vs −1.5, p=0.003) was significant between the two groups. After adjusting for time from HIV diagnosis and years of ART, study group was the only factor associated to higher mean percentage change from baseline femoral BMD (MVC+DRV/r +4.83, p=0.044).ConclusionsThe study demonstrated a significant improvement in femoral BMD and T‐score after treatment simplification with MVC+DRV/r.