bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV‐1 drug resistance‐associated mutations among antiretroviral‐naïve Thai patients with chronic HIV‐1 infection
Authors: Manosuthi W , Thongyen S , Nilkamhang S , Manosuthi S , Sungkanuparph S 
Published: November 2012

Purpose of studyAntiretroviral therapy (ART) has been scaled up in resource‐limited settings. This study aimed to determine the prevalence of HIV‐1 drug resistance‐associated mutations (DRAMs) among patients with chronic HIV‐1 infection and to compare DRAMs between CRF01_AE and B subtypes.MethodsART‐naïve Thai patients who were indicated for ART initiation between 2010 and 2011 were prospectively enrolled. Genotypic assays of reverse transcriptase and protease genes were performed within 4 weeks prior to ART. DRAMs were assessed using International AIDS Society USA 2011 list.Summary of resultsA total of 330 patients were included. HIV‐1 subtypes included CRF01_AE (241, 73.0%), B (79, 23.9%), and others (10, 3.1%). Median (IQR) CD4 was 66 (23–172) cells/mm3 and median (IQR) HIV‐1 RNA was 5.2 (4.6–5.8) log copies/mL. The prevalence of patients with≥1 DRAMs to any antiretroviral agents was 17.6%; 17.0% to NNRTIs, 0.6% to NRTIs, and 0.6% to protease inhibitors (PIs). V106I (23, 7.0%), V179D (14, 4.2%), V179T (6, 1.8%), E138A (5, 1.5%), V90I (4, 1.2%), K103N (3, 0.9%), Y181C (3, 0.9%), and P225H (1, 0.3%) were DRAMs to NNRTIs. M184V (1, 0.3%) and T215S (1, 0.3%) were DRAMs to NRTIs. M46L (2, 0.6%) was the only major DRAM to PI. Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were more frequently observed in CRF_01 AE but A71V/T and V77I were more common in subtype B (P < 0.05). By multivariate analysis, the factors ‘HIV‐1 subtype B’ and ‘low pretreated CD4 cell count’ were associated with higher rate of DRAMs.ConclusionHIV‐1 DRAMs, especially to NNRTIs, is emerging in a middle‐income country after a widespread use of NNRTI‐based ART. HIV genotypic assay prior to ART initiation in patients with chronic HIV‐1 infection should be considered.
3TC+ PI dual therapy during pregnancy for PMTCT of HIV‐1‐naïve or pretreated women
Authors: Gliga S , Clavel C , Alix A , Dommergue M , Quetin F , Marcelin A , Stitou H , Schneider L , Calin R , Caby F , Valantin M , Mellon G , Seang S , Katlama C , Tubiana R 
Published: November 2012

Purpose of the studyPerinatal transmission of HIV has fallen dramatically in countries where access to antiretrovirals is available, placing the focus of research on safety. The aim of this study is to assess whether in naïve or pretreated HIV‐1 women, a dual, zidovudine sparing regimen (3TC+ PI) initiated during pregnancy can control maternal viral load while preventing maternal and infant toxicities related to in utero exposure to zidovudine.MethodsWe performed a retrospective, descriptive study between January 2006 and 2012. Seventeen naïve and 28 pretreated women who received dual therapy (3TC + PI) during pregnancy were included in the studied group and compared to 49 women on standard triple therapy (3TC/ ZDV+ PI), who delivered in the same time interval, at the same hospital. The primary endpoint was the% of women with viral loads (VL) ≤ 50 cp/ml at delivery. Secondary endpoints included% of women with VL ≤ 400 cp/ml after one month of dual therapy and of women who remained under dual therapy until delivery and achieved a VL ≤ 50 cp/ml at delivery. We also compared safety outcomes during pregnancy and until 18 months in children.Summary of resultsGroups had indistinguishable median VL at day zero (200 vs. 1680, p = 0.29) and gestational ages at initiation of therapy (19.6 vs 18 weeks, p = 0.18). At initiation of dual therapy (in 80% of cases: 3TC + LPV/r; ATV/r or ATV), the median VL was 21,692 cp/ml (6589 to 31,269) for naïve women and 43 cp/ml (20 to 200) for pretreated women. In intent‐to‐treat analysis of the dual therapy group, 41/45 women (91.11%, 95% CI 78.7 to 97.5%) achieved their primary endpoint. The table presents proportions of viral success at primary and secondary endpoints in the dual (N = 45) and control (N = 49) groups. Groups had similar proportions of cesarean section (28.8% vs 34.7%, p = 0.65) and of prematurity and changes in ART due to intolerance. There was one case of MTCT for the controls and none in the dual therapy group. Newborns with prenatal ZDV exposure had higher proportions of clinical syndromes at birth (50% vs 25%, p = 0.02) and SAE in the first 18 months of life (90.3% vs 68.2%, p = 0.05) and worse haematological values at birth, with lower levels of haemoglobin (15.6 vs 17.5 g/dl, p = 0.05).

ITT
3TC+PI
3TC/ZDV+PI

p

VL at delivery

<50
91.1%
88.5%
0.72

VL at M1

<400
91.1%
73.4%
0.03

Virological success and maintained therapy p

VL at delivery

<50
82.2%
85.7%
0.76

ConclusionsThe 3TC+ PI dual therapy strategy in naïve or pretreated women achieved a satisfactory virologic effectiveness and resulted in less SAE in the first 18 months of life and better haematological parameters at birth for children.
First‐line antiretroviral treatment outcome in a patient presenting an HIV‐1/2 multiclass drug resistant infection
Authors: Castro E , Recordon‐Pinson P , Papuchon J , Vetter B , Shah C , Schupbach J , Fleury H , Cavassini M 
Published: November 2012

BackgroundWith the expansion of HIV‐2 epidemic beyond African countries, co‐infection with HIV‐1 becomes a global challenge. We have recently identified an HIV‐1/2 dual infection with both viruses bearing multiclass drug resistance in an untreated patient [1]. We now present the patient's combined antiretroviral treatment (cART) outcome after 6 months follow‐up.Patient and MethodsClinical samples were obtained upon informed consent from a 23‐year‐old man living in Guinea‐Bissau until March 2011 when he moved to Switzerland. As previously reported [1], HIV‐1/2 co‐infection was confirmed by HIV‐1 PCR (21.000 copies/ml) and total HIV‐1/2 viremia (4.351 nU/ml) by product‐enhanced reverse transcriptase (PERT) assay. The patient denied previous HIV testing or exposure to antiretroviral drugs. Dual infection consisted of HIV‐1 CRF02_AG bearing resistance mutations M184V/V90I and HIV‐2 clade A, harboring K65R/D67N mutations as amplified from proviral‐DNA. Baseline CD4 + T‐cell count was 408 cell/mm3. We initiated cART in accordance to drug resistance mutations (see below). Treatment compliance was assessed with an electronic pillbox device and drug‐plasma concentrations. Clinical and laboratory follow up were done at weeks 2, 4, 9, 12 and 24.ResultscART was initiated with tenofovir/emtricitabine (TDF/FTC), boosted‐darunavir (DRV/r) and raltegravir(RAL). Treatment compliance was fluctuant during the first 3 months after which it remained stable with an average monthly intake of 92%. Antiretroviral drug‐plasma concentrations were traced at percentile 25th. HIV‐1 viremia became undetectable at week 12. Additionally, HIV‐2 viremia was retrospectively assessed by real‐time RT‐PCR at two independent laboratories showing undetectable values across the study period including baseline. Thus, baseline viremia, as assessed by the PERT test for particle‐associated reverse transcriptase activity was due to HIV‐1 alone. CD4 + T‐cell count was 559 cell/mm3 at week 24. Laboratory assessments showed a neutrophile drop to 0.96 at week 4, fully restored at week 9.ConclusionThis case of HIV‐1/2 dual infection underscores the importance of assessing genotypic analysis of both viruses ahead to treatment choice. It also highlights viral load platforms constraints when it comes to clinical monitoring of HIV‐1/2 co‐infection in western settings. Overall, first‐line salvage treatment was well tolerated and suppressed HIV‐1 resistant clade allowing recovery of CD4+ T‐cell count.
Impact of antiretroviral dosing frequency and daily pill burden on virological success rates in patients of the ICoNA cohort starting their first ART
Authors: Ammassari A , Lorenzini P , Mussini C , Cozzi‐Lepri A , Baldelli F , Gori A , Andreoni M , Tozzi V , Di Perri G , Lazzarin A , Quirino T , Cassola G , d'Arminio Monforte A , Antinori A 
Published: November 2012

Complexity of antiretroviral treatment (ART) is a reason for non‐adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low‐pills QD [lpQD]); 3–6 daily pills QD (high‐pills QD [hpQD]); 2–5 daily pills BID (low‐pills BID [lpBID]); >6 daily pills BID (high‐pills BID [hpBID]). VS was the date of first HIV RNA <50 cp/ml. Follow‐up was censored at the date of VS or last available HIV RNA. Kaplan‐Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44); HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre‐ART CD4 and log HIV‐RNA were 271/mm3 (range, 0–1672) and 4.84 cp/ml (1.70–6.38), respectively. Regimens were started in ‘00–‘02 24%,‘03–‘05 17%,‘06–‘08 17%,‘09–‘12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8). Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan‐Meier curves are shown (Figure).imageAfter stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre‐cART CD4 and HIV‐RNA, type of regimen a significantly reduced likelihood of achieving VS was found for ART complexity (hpQD: HR 0.76 95% CI 60–0.96; lpBID: 0.74, 0.59–0.94) when compared with lpQD. The chance of VS was higher in people starting ART more recently (RH 1.28 [95% CI 1.09–1.51] for ‘03–‘05; RH 1.64 [1.27–2.10] for ‘09–‘12; vs. ‘00–‘02) and was lower in people with previous AIDS (RH 0.85 [0.73–0.98]). Once‐a‐day dosing of ART, especially when combined with low daily pill burden, seems to be one of main factors contributing to the higher rate of success of ART in recent years.
Four‐drug induction regimen for patients with high baseline viral load
Authors: Masini G , Bernardini C , Cologni G , Soavi L , Astuti N , Di Filippo E , Benatti S , Maggiolo F 
Published: November 2012

Early virologic changes after treatment have been associated with long‐term virologic success. The objective of this pilot, randomised, prospective study is to evaluate the effect of an induction, 4‐drug HAART regimen in patients with high baseline viral load. Twenty‐one naïve patients with HIV‐RNA>100,000 copies/ml were randomised to TDF+FTC+EFV (1); TDF+FTC+EFV+RAL (2), TDF+FTC+RAL (3). Viral load, CD4 and immune activation markers were evaluated at days 7, 14, 30, 60, 120 from the start of therapy. Mean age was 38.2 years, 19 (90.5%) were male, and the main risk factor for HIV infection was heterosexual contacts in 52.4% of patients. The mean baseline viral load was 265,266 copies/ml and the mean CD4 cell count was 314 cell/mm3. CD8+CD38+HLA‐DR+ cells mean was 38%. No difference was observed among the three groups. Early HIV‐RNA reduction was significantly higher in group 2 at day 7 (P=0.007), 14 (P=0.018), 30 (P=0.046) after HAART start, thereafter HIV‐RNA values were comparable among the groups. No significant differences were observed at any time‐point between group 1 and group 3. The viral decay (delta VL), evaluated as reduction of viral load, was faster and higher in group 2 at any time‐point; the reduction was statistically significant (compared to group 1 and 3) after 7 days (P=0.006), but not thereafter. No differences were observed between group 1 and 3 (Figure, panel A). At the end of follow‐up (120 days) only patients in group 2 reduced HIV‐RNA below<3 copies/ml in 30% of cases. Although not statistically significant (probably because of the small sample) immune recovery, as measured by the increment of CD4 cells, was greater in the two groups receiving RAL (Figure, panel B). At the end of the follow up the mean increment was 142 cells/mm3 in group 1; 258 cells/mm3 in group 2 and 360 cells/mm3 in group 3. No difference was observed as far as the reduction of immune activation is concerned. A 4‐drug regimen in naïve patients with high pre‐therapy viral load improves early virologic response, that has been proved to be a prognostic marker for sustained virologic response. CD4 cell recovery is much higher in patients receiving RAL compared to those treated with EFV. This study highlights the importance of a personalised therapy especially in high‐risk patients. Further studies are necessary to define the best therapeutic regimen in patients with high baseline viral load.image
Antiretroviral therapy in naïve Romanian HIV patients
Authors: Arbune M , Benea O 
Published: November 2012

BackgroundThe peculiarity of Romanian HIV epidemic is the high number of long‐time survivors, nosocomially infected with F subtype during early childhood. Although ART is provided for free, patients from certain regions are difficult to attain viral load (VL) and HIV resistance tests.ObjectivesTo assess the durability of first‐line antiretroviral therapy (1st ART) in Romanian HIV patients.MethodsRetrospective assessment of new HIV diagnosed patients during 2005–2010, monitored every 24 weeks (wk) in HIV clinic from Galati ‐ Romania, considering demographic data, HIV transmission pattern, immunity, HIV‐RNA blood levels, co‐morbidities, 1st ART regimen and adherence according to the national protocol. The endpoint was term on loss to follow‐up, death or 96 wk of ART.Results100 new diagnosed HIV patients since 2005 received 1st ART. Characteristics of naïve patients: median age on HIV diagnostic=22.5 years old; sex ratio M/F=53/47; living area rural/urban=55/45; low literacy 26%; HIV infection pattern paediatric/ sexual/ unknown=29/61/10; advanced late presenters 51%; TB as HIV indicator 22%; VHB co‐infection 22%; baseline av. CD4Ly=171/mm3. Experience of 1st ART: 2 NRTI+EFV 38% or LPV 27% or other protease inhibitor 35%. The reasons for 58% interrupting 1st ART: 9% dead, 17% abandoned, 18% failed, 12% developed adverse events and 2% drug‐drug interactions. While 53% patients were adherent previous to endpoint, no more than 42% kept on 1st ART>96 wk and recovered immunity with av. CD4Ly=213/mm3. Poor recovery of CD4Ly<100/mm3 was acquired by 13/48 patients with available HIV‐RNA<50 c/ml in 48 wk. The main risks below 24 weeks of 1st ART are the death (p=0.005; OR=36) and the adverse events (p=0.018; OR=24). Abandon rate (p=0.016; OR=5.14) is higher over 48 weeks. Regardless of 1st ARV regimen, adherence behaviour, immunologic benefits and ART durability were comparable. Viral failure is related to non‐adherence (p=0.03; OR=4.5) and low literacy situation (p<0.001; OR=7.5). Mortality is 4.6 times higher in TB and 2 times in HBV co‐morbidities.ConclusionsOver a half of naïve HIV patients continued 1st ART less than 96 wk. 26% patients with low literacy are a vulnerable group and require individualised educational and adherence programmes. To improve the sustainability of the 1st ART in HIV patients from Galati needs to intensify the support for earlier HIV diagnostic and current virology follow‐up.
Effectiveness of ritonavir‐boosted protease inhibitor monotherapy in routine practice
Authors: Fonquernie L , Lefebvre B , Valin N , Morand‐Joubert L , Boyd A , Meynard J 
Published: November 2012

BackgroundRecent trials have shown the potential benefits of ritonavir‐boosted protease inhibitor (PI/r) monotherapy. As this alternative strategy has recently been included in European HIV treatment guidelines, its effectiveness needs to be assessed in routine practice.MethodsFrom 1st January to 31 December 2011, we identified all patients receiving a current PI/r monotherapy at a university‐based hospital setting using the Diamm database system. Antiretroviral‐naïve patients who directly initiated PI/r monotherapy were excluded. Patients who continued PI/r monotherapy after ending participation in a clinical trial were also included. We performed a retrospective, descriptive analysis of demographic, clinical and therapeutic characteristics of these patients. For biological variables, the last available value in 2011 was retained.ResultsIn 2011, among 3140 antiretroviral‐treated patients in our department, 107 (3.4%) received PI/r monotherapy (lopinavir/r n = 58, darunavir/r n= 49). Of them, 30 (28%) started during 2011 and 31 (29%) continued after a prior trial. Two patients switched to DRV/r due to intolerance. Eighty‐eight percent were male and median age at initiation was 45 years. The median time from starting multitherapy and switching to monotherapy was 30 months (range 2–117). At PI/r monotherapy initiation, median CD4 count was 567 cells/mm3 and HIV RNA was below 50 copies/mL in 90% of patients. The median duration under PI/r monotherapy was 25.4 months (range 0.5–93). At the end of follow‐up, median CD4 count was 643 cells/mm3 and HIV RNA was below 50 copies/mL in 89% of cases. During 2011, 11 patients discontinued PI/r monotherapy, of whom 8 presented viral rebound. Only one patient exhibited major protease mutations. All these 8 patients achieved an undetectable viral load 3 months after therapeutic intensification.ConclusionThis descriptive analysis shows that PI/r monotherapy in routine practice could be considered as an alternative and successful maintenance strategy, especially among patients who achieved an undetectable viral load while undergoing prior multitherapy.
High viral load, previous fosamprenavir use and more recent HIV diagnosis correlate with darunavir failure in salvage therapy in Sao Paulo, Brazil
Authors: Schöntag M , Tenore S , Ferreira P , Guinoza J , Diaz R 
Published: November 2012

Purpose of the studyEfficacy of DRV‐containing regimen in antiretroviral‐experienced patients in Brazil is unknown. The aim of this study was to evaluate the prevalence and risk factors associated with virologic failure (VF) to DRV containing salvage regimen in experienced HIV‐infected patients in Sao Paulo and also determine the prevalence of DRV resistance associated mutations (RAM) in this population.MethodsRetrospective study of 131 patients who started a DRV‐containing salvage regimen between 12/2007 to 12/2009 in 2 centers in Sao Paulo. Protease resistance mutations listed by 2011 IAS‐USA panel update were considered. Genotypic sensitivity score (GSS) was calculated for the proposed regimen using the 2008 Rega algorithm. We have assessed VF during 48 weeks of follow up and VF was defined as the failure to achieve viral suppression in 48 weeks or viral rebound after suppression. Stopping the use of DRV for any reason was also considered VF.Summary of resultsWe analysed 131 patients, 71% male, median age 44y. More than half of the patients had a baseline CD4 cell count<200/mm3 (58,9%) although only 21,4% presented a VL ≥100.000 copies/ml. 78,6% had previous used more than 2 PI and more than half of the patients harbored viruses with at least 11 IAS PI resistance mutations (59,5%) The majority of patients had less than 2 DRV RAM (84,7%) and the most prevalent major and minor DRV RAM were respectively I84V (24,4%) and L33F (34,3%). Most patients (79,4%) have received more than 2 active drugs in their regimen. Twenty patients (15,3%) have failure in achieving VL <50copies/ml at 48 weeks. Ten patients were lost of follow up and the remaining 10 were treatment failure. In multivariate analysis, VL≥ 100.000 copies/mL (p=0,002), less than 15 years of HIV diagnosis (p=0,013) and previous fosamprenavir use (p=0,027) were independently predictive of VF.ConclusionsThis study, conducted in routine clinical conditions, is probably the large cohort to evaluate risk factors to VF with DRV containing regimen worldwide and is the first one to evaluate prevalence of VF with DRV containing regimen in Brazil. We found an elevated response rate in this population (84,7%) which couples with the low number of DRV RAM despite the elevated number of previous PI used and by the high GSS. The factors associated with VF were similar to previous reports except for the time of HIV diagnosis, and one can speculate that this correlates with lower adherence in this group.
Novel Kivexa‐based regimens in early courses of treatment for HIV infection
Authors: Conway B , Alenezi O , Wong L , Wang J , Qian C , Tossonian H 
Published: November 2012

BackgroundAs the long‐term efficacy of antiretroviral therapy regimens is confirmed, we need to identify additional combinations with long‐term safety and potency, while also favoring simplicity of administration. In this light, we have undertaken a review of the use of abacavir/lamivudine (Kivexa, KVX)‐based regimens using integrase or CCR5 inhibitors as the third agent.MethodsA retrospective chart review was undertaken, with informed patient consent. We identified all the patients in whom KVX was prescribed (following appropriate HLA‐B5701 screening) with either raltegravir (RGV) or maraviroc (MVC) as initial therapy or as a switch from another regimen for reasons other than virologic failure. Virologic efficacy over 48 weeks was evaluated, along with specific drug‐associated toxicity, adherence, and regimen modifications.ResultsA total of 38 patients (5 women) were evaluated, 24 on KVX/RGV, 13 on KVX/MVC, 1 on KVX/RGV/MVC. This was used as initial therapy in drug‐naïve subjects in three cases, and was selected as a modification of previous (current or not) therapy in 35 cases. Switches included replacement of the third agent with RGV or MVC (n=13), replacement of the NRTI backbone with KVX (n=13) or both. In all cases, the change was implemented to address a current or previous medication‐associated toxicity, most commonly to address jaundice (n=8), diarrhea (n=5) or reduced renal function (n=5). Patients were predominantly MSMs (n=17) or IDUs (n=13) with a mean baseline CD4 cell count of 363 cells/mm3, and plasma viral load of 46407 copies/mL (20 with full suppression at time of study entry). At 48 weeks, 34/38 (89%) achieved or maintained full suppression, with a mean CD4 count of 553 cells/mm3. Virologic failure with the development of the M184V mutation was observed in 3/4 non‐suppressed patients, and a loss of CCR5 tropism and RGV resistance were observed in one case each, all in the context of reduced adherence. There were no treatment discontinuations for toxicity and no medication‐associated serious adverse events.ConclusionKVX‐based regimens are safe and effective alternatives to more commonly used regimens in clinical practice, and offer the benefit of good long‐term tolerability and little or no need to enhance follow‐up for laboratory‐based abnormalities. Consideration should be given to non‐NNRTI and non‐PI‐based regimens to address issues of toxicity and simplification without apparent loss of efficacy.