bluuebunny/crossref_metadata_2025 huggingface dataset:
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 study

Perinatal 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.

Methods

We 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 results

Groups 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

Conclusions

The 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

Background

With 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 Methods

Clinical 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.

Results

cART 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.

Conclusion

This 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).

image

After 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.
Compliance with HIV treatment guidelines in the Spanish CoRIS cohort: impact on mortality and immunovirological response
Authors: Suárez‐García I , Sobrino‐Vegas P , Tejada A , Viciana P , Montero M , Berenguer J , Oteo J , Díaz González J , Pineda J , del Amo J , Moreno S
Published: November 2012

There is little evidence assessing compliance with clinical practice guidelines for antiretroviral treatment and its impact on clinical outcomes. The Spanish national guidelines for antiretroviral treatment are published by the Spanish AIDS Study Group (GeSIDA). The aim of this study was to assess compliance with national guidelines for the treatment of naïve patients from a multicentre Spanish cohort (CoRIS). The specific aims were to evaluate the proportion of patients treated according to the guidelines’ recommendations, to investigate factors associated with the prescription of a non‐recommended treatment, and to assess the impact of non‐recommended treatments on mortality and on virological and immunological response (defined as undetectable viral load and increase of 100 CD4/ml, respectively, after 1 year). Drug combinations were classified as recommended, alternative, or not recommended, according to the guidelines’ “what to start with” recommendations. 6225 naïve patients were included between the years 2004 and 2010. Among 4516 patients who started treatment, 3592 (79.5%), 540 (12%), and 384 (8.5%) started with a recommended, alternative and not‐recommended treatment, respectively. The use of a not‐recommended treatment was significantly associated with CD4 count >500/ml (OR: 2.03, 95% CI: 1.14–3.59), hepatitis B infection (OR: 2.23, 95% CI: 1.50–3.33), treatment in a hospital with <500 beds, and starting treatment in the years 2004 to 2006. There was no significant association of having a not‐recommended treatment with gender, route of transmission, hepatitis C infection, country of origin, education, or viral load. The use of a not‐recommended regimen was significantly associated with mortality (HR: 1.61, 95% CI: 1.03–2.52, p=0.035) and lack of virological response (OR: 0.65, 95% CI: 0.45–0.93, p=0.019), but it was not associated with immunological response (OR: 0.90, 95% CI: 0.75–1.08, p=0.273). In conclusion, compliance with “what to start with” recommendations of Spanish national guidelines was high. The use of not‐recommended regimens was more likely in patients with >500 CD4/ml, hepatitis B infection, and starting treatment in the years 2004–2006 and in small hospitals. Not‐recommended regimens were associated with higher mortality and lack of virological response.
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

Background

The 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.

Objectives

To assess the durability of first‐line antiretroviral therapy (1st ART) in Romanian HIV patients.

Methods

Retrospective 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.

Results

100 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.

Conclusions

Over 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

Background

Recent 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.

Methods

From 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.

Results

In 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.

Conclusion

This 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.
Open‐label study of maraviroc+lamivudine/zidovudine in treatment‐naïve adults infected with HIV‐1, predominantly subtype A, by population genotyping
Authors: Portsmouth S , Valluri S , Craig C , Lewis M , Pokrovsky V , Gartland M , Heera J
Published: November 2012

HIV‐1 subtype A infection predominates in Russia; however, little experience of response to maraviroc in this subtype exists and population genotyping in this setting requires further exploration. One hundred and twenty‐one treatment‐naïve HIV‐1‐infected individuals from seven centres in Russia were screened using V3 loop population genotyping with a false‐positive rate of 10% (geno2pheno); 75% of patients were confirmed to have CCR5 (R5)‐tropic HIV‐1, 21% of patients had non‐R5 HIV‐1, and 4% of tests were non‐reportable. Seventy‐seven patients met the inclusion criteria and were treated with maraviroc 300 mg twice daily (BID) in combination with lamivudine/zidovudine. Virologic and immunologic responses were assessed in this 24‐week planned interim analysis. Fifty‐one male (66.2%) and 26 (33.8%) female patients were enrolled. In total, 76.3% of patients had subtype A infection, and 28.6% were co‐infected with hepatitis C virus. At baseline, the mean (± standard deviation [SD]) CD4 count was 404±122 cells/mm3, and the mean viral load was 4.77±0.74 log10 copies/mL, with 38% of patients having viral loads ≥100,000 copies/mL. At Week 24, 80.5% of patients had viral loads <50 copies/mL and the mean (±SD) CD4 cell count was 411±124 cells/mm3. No treatment‐emergent adverse events were attributed to maraviroc, and three patients experienced Grade 4 anaemia associated with lamivudine/zidovudine. Seven patients discontinued from the study, but only one of these discontinuations was due to an insufficient clinical response. Two patients had 3TC resistance at the time of discontinuation. Virologic responses to a maraviroc‐based regimen in patients infected with R5‐tropic HIV‐1 subtype A, determined using population genotyping, were confirmed.
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 study

Efficacy 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.

Methods

Retrospective 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 results

We 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.

Conclusions

This 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.
SPIRIT: switching to emtricitabine/rilpivirine/tenofovir DF single‐tablet regimen from boosted protease inhibitor maintains HIV suppression at week 48
Authors: Fisher M , Palella F , Tebas P , Gazzard B , Ruane P , van Lunzen J , Shamblaw D , Flamm J , Ebrahimi R , White K , Guyer W , Porter D , Fralich T
Published: November 2012

Antiretroviral regimen simplification improves quality of life and medication adherence while reducing the risk of HIV virologic failure (VF) and long‐term drug‐related toxicities. Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) is a well‐tolerated and efficacious once‐daily single‐tablet regimen (STR) treatment option. Here we report the Week 48 safety and efficacy results of SPIRIT, the first study to evaluate switching from boosted protease inhibitor (PI+RTV)‐based HAART to a simplified regimen of FTC/RPV/TDF STR. SPIRIT is a phase 3b, randomized, open‐label, multi‐center, international, 48‐week study to evaluate the safety and efficacy of switching from PI+RTV regimens to FTC/RPV/TDF in virologically‐suppressed HIV‐1 infected participants. Participants were randomized 2:1 to switch to FTC/RPV/TDF at baseline or maintain their current PI+RTV regimen with a delayed switch to FTC/RPV/TDF at Week 24. The primary endpoint was non‐inferiority (12% margin) of FTC/RPV/TDF relative to PI+RTV regimens in maintaining plasma HIV‐1 RNA<50 copies/mL at Week 24 by FDA snapshot analysis. Plasma HIV‐1 RNA levels were assessed at screening, baseline, and at Weeks 4, 8, 12, 24, (28 and 32 for delayed switch participants), 36, and 48 or early termination. A total of 476 participants were randomized and received at least 1 dose of study drug (317 FTC/RPV/TDF; 159 PI+RTV+2NRTIs). Baseline characteristics were similar across treatment arms. The primary endpoint of non‐inferiority at Week 24 was met (HIV‐1 RNA <50 copies/mL by FDA snapshot analysis 93.7% FTC/RPV/TDF vs. 89.9% PI+RTV+2NRTIs; difference 3.8%, 95% CI: −1.6 to 9.1]). Through Week 48, 88.3% of subjects switching to FTC/RPV/TDF at baseline maintained virologic suppression (HIV‐1 RNA<50 copies/mL by FDA snapshot analysis). The rate of virologic suppression at Week 48 for the 152 participants who switched to FTC/RPV/TDF at Week 24 was comparable to the rate of virologic suppression at Week 24 for those who switched to FTC/RPV/TDF at baseline (delayed switch to FTC/RPV/TDF 92.1%; baseline switch to FTC/RPV/TDF 93.7%). In the Week 48 analysis of SPIRIT, the first study to evaluate switching to FTC/RPV/TDF STR from a PI+RTV‐based regimen in virologically‐suppressed, HIV‐1‐infected participants, virologic suppression was maintained regardless of whether participants switched to FTC/RPV/TDF at baseline or at Week 24.
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

Background

As 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.

Methods

A 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.

Results

A 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.

Conclusion

KVX‐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.
Safety and efficacy of once‐daily single generic fixed‐drug combination tablet of tenofovir, lamivudine and efavirenz among HIV‐infected Thais
Authors: Maek‐a‐Nantawat W , Avihingsanon A , Thainsanguankul W , Wongsabut J , Gorowara M , Ramautarsing R , Clarke A , Hsu D , Ruxrungtham K
Published: November 2012

Background

Generic fixed dose combinations (FDCs) of nucleoside reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) is commonly used in resource‐limited settings to increase adherence to lifelong treatment. However, the cumulative evidence of the long‐term complications, particularly mitochondrial toxicity of NRTIs, especially stavudine (or zidovudine), brings about widespread use of tenofovir (TDF). This study was aimed to assess the efficacy and safety of a FDC comprising 300 mg tenofovir (TDF), 300 mg LAM and 600 mg efavirenz (EFV).

Methods

A Phase II open‐label clinical trial was conducted at HIV‐NAT, Thai AIDS Research Center, Thai Red Cross from April 2010 to December 2011. Patients were eligible to enroll if they were either: 1) on TDF, LAM and EFV as separate tablets, for at least 6 months with an undetectable viral load (= switch arm) or 2) treatment‐naïve. Safety profiles, including liver and renal functions, were assessed at baseline, weeks 4, 12, 24 and 48. In switch group, mid‐dose TDF plasma concentrations were measured by HPLC at baseline and week 4 after a switch to single FDC tablet.

Results

A total of 100 patients were enrolled (51 naïve). Median age was 34 years and 30% were female. The median baseline CD4 cell count (IQR) was 512 (395–620) cells/L and 232 (164–284) cells/L for the switch arm and ARV‐naïve group, respectively. The median (IQR) log10 HIV‐1 RNA for ARV‐naïve group was 4.9 (4.2–5.3) copies/mL. By ITT analysis, the proportion of cases with HIV RNA<50 copies/mL was 93% and 92% at week 24 and 48, respectively. Only 1 confirmed virological failure at week 12 with NNRTI‐resistant mutations (A98G, K103N, V118I, E138Q, Y181C). The reported 3 SAEs (severe headache, infective endocarditis, cervical dysplasia) were found and one was possibly related to the study drug. There were 49 mild to moderate efavirenz‐related central nervous system events, occurring in first few days‐weeks. There were no statistically significant changes on renal function and liver enzymes. Mean plasma concentrations of all three drugs in FDC met the acceptable target levels.

Conclusion

The generic FDC of TDF/3TC/EFV was well tolerated and efficacious. Our findings lend support to the use of this generic FDC as first‐line antiretroviral therapy in resource limited settings.
HIV2 late presenters in an infectious disease ward: six years’ experience
Authors: Pires D , Zagalo A , Antunes F
Published: November 2012

Purpose of the study

About a third of HIV‐infected patients in Europe present for care late in their disease. In 2010 a consensus was reached for a definition of late presentation, providing a new tool for research and acting. With regard to HIV2 infection this population has never been characterized.

Methods

Retrospective analysis of the clinical records of all the HIV2‐infected patients who meet the inclusion criteria (those defined by the European Late Presenter Consensus working group: Late presentation of HIV infection: a consensus definition 1) admitted to our ward between January 2006 and December 2011. The patients were characterized according to epidemiological, clinical and immunologic status and outcome.

Summary of results

During the period analyzed, 15 HIV2 patients were late presenters. The mean age of the patients was 48 years old (although 53% were older than 50 years); 8 (53%) were men; 11 (73%) were of African origin. Heterosexual transmission was reported in three of the patients, in the remainder the transmission mode was not available. The mean TCD4 cell was 188 (range 27–339), with 8 (53%) with a CD4 count below 200 cells. Twelve (80%) of the patients fulfilled AIDS criteria. There were 3 deaths, corresponding to a mortality rate of 20%. The cause of death was disseminated tuberculosis in two cases and non‐Hodgkin's lymphoma in the third case.

Conclusions

Most late presenters with HIV2 infection are of African origin, there is an even distribution between genders, their mean age is around 50 years old, more than half had a CD4 cell count below 200 and there was a 20% mortality rate. These patients pose challenges at various levels: their mortality rate is much higher than in the general HIV‐infected population and they are diagnosed very late, leading to a disproportionate increase in risk of transmission, morbidity and mortality.
Women in Serbia as late presenters‐an issue of concern
Authors: Dragovic G , Ranin J , Salemovic D , Kusic J , Jevtovic D
Published: November 2012

Most of the clinical trials looking at the efficacy and side effects of highly active antiretroviral therapy (HAART) have been conducted primarily on HIV‐infected males. So, we conducted a study to determine the factors influencing prognosis of HIV/AIDS and outcome in HIV/AIDS women on HAART, in a resource‐limited settings. A cross‐sectional study was performed on women, with HIV infection, who initiated HAART between 1st January 1998 and 31st December 2010, at the HIV/AIDS Center of the University Hospital for Infectious and Tropical Diseases in Belgrade, Serbia, with regular clinical and laboratory check‐ups. SPSS‐version‐11.0 software, Univariate and stepwise Multivariate logistic regression analysis together, with the Kaplan‐Meier analysis, were used to estimate risk factors influencing prognosis and outcome in HIV/AIDS women. Written consent was obtained. A total of 230 women were followed for 8.2±3.4 years (range 1–12). Durring the follow‐up, 26 patients died. The mean age of the patients at HAART initiation was 37±9.7 years. Clinical AIDS at presentation was observed in 43.9% of the patients, while 80% of them had CD4 cell counts below 200 cell/mm3. Univariate and stepwise multivariate analysis have shown that the progression to death was associated with basal CD4 counts below 100 cells/µL (OR 3.0 95% CI 1.7–8.4, P=0.02) and HCV co‐infection (OR 2.6 95% CI 1.0–6.6, P=0.03). However the NNRTI based regimens and good adherence to HAART (OR 0.2, 95% CI 0.09–0.6, P=0.005 and OR 0.3, 95% CI 0.1–0.66, P=0.03, respectively), all prevented death. Although in patients with sustained viral suppression the CD4 counts varied significantly, these did not affect overall survival (p=0.21, log rank) If HIV infected women with advanced HIV‐related immunodeficiency reach and maintain optimal viral suppression during HAART, regardless of the level of immune recovery, and if they continue to maintain this achievement up to a mean 8 years of treatment, their prognosis may be fairly good even in a resource limited settings.
TRANxITION 144‐week results: switching virologically stable HIV patients from immediate‐release nevirapine (NVP IR) to extended‐release NVP (XR)
Authors: Arastéh K , Drulak M , Guo J , Livrozet J , Orkin C , Quinson A , Ward D
Published: November 2012

Purpose of the study

TRANxITION compared the efficacy and safety of switching virologically suppressed patients from NVP IR (200 mg BID) to NVP XR (400 mg QD) and demonstrated the non‐inferior efficacy of NVP XR in virologically suppressed patients. Here, post‐48‐week safety and efficacy results of patients initially randomized to NVP IR and allowed to switch to NVP XR after 48 weeks, were compared to patients on NVP XR throughout the study.

Methods

TRANxITION was an open‐label, parallel‐group, non‐inferiority clinical trial where adult HIV‐1 patients receiving NVP IR plus a fixed‐dose NRTI combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV), with undetectable viral loads (VL) were initially randomized (2:1) to NVP XR or NVP IR. After week 48, patients initially randomized to NVP IR were allowed to switch to NVP XR. Primary endpoint was continued virologic suppression (VL<50 copies/mL) at week 24. Secondary endpoints included long‐term follow‐up at 48 and 144 weeks.

Summary of results

At week 48, proportions of patients with virologic response (LLOQ = 50 copies/mL TaqMan, FAS) were 88.5% (131/148) NVP IR BID arm, and 88.8% (262/295) NVP XR QD, with an observed difference of 0.3% (95% CI −6.1, 6.7). Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups at week 48, 6.4% (19/295) vs. 6.1% (9/148) respectively, although serious AEs were slightly higher in the NVP XR group (10.2%, 30/295, vs. 8.1%, 12/148 for the NVP‐IR group). After week 48, all but 13 patients in the NVP IR arm switched to NVP XR. At week 144, proportions of patients with virologic response were 115/121 (95.0%, patients switching from IR to XR after week 48 [IRpost48XR]), and 238/250 (95.2%, patients on XR throughout [XRpost48]). DAIDS grade 3 and 4 events were similar for both post‐week‐48 XR groups at week 144, with (10/130, 7.7%, [IRpost48XR] vs. (31/276, 11.2% [XRpost48]), while serious AEs were higher in the XRpost48 patients (54/276, 19.6% vs. 17/130, 13.1% for the IRpost48XR group).

Conclusions

NVP XR QD resulted in continued virologic suppression at weeks 48 and 144. While fewer patients remained in the study post‐week 48, both XR groups had high virologic response rates. Rates of serious AEs were modestly higher than seen at week 24 in both post‐week‐48 XR arms up to week 144, most likely due to the open‐label design of the study.
Reasons for antiretroviral treatment changes in Spanish HIV 1 patients in 2011: SWITCH AUDIT study
Authors: Tasias M , Viciana P , Deig E , Arranz J , Pasquau J , Vera F , Pujol E , Vergas J , Bernardino J , Pedrol E
Published: November 2012

Background

Until the past decade, immune/viral failure was the main reason for antiretroviral treatment changes. After HAART generalization the management of antiretroviral treatment toxicities was the most prevalent reason for treatment modification. Today, with the advent of new more potent and less toxic drugs as well as more convenient combinations may have changed the situation. We aim to describe the main reasons that today leads to ART changes in HIV+ patients in Spain in the current clinical practice.

Methods

Multicentre, national, cross‐sectional epidemiological study. Eligible patients had to be HIV+, >18 years old and under current ART that was going to be changed by any reason. Patients did sign inform consent. The study consisted in a single visit (change of treatment) in which data on social and demographic characteristics, HIV disease and ARV treatment were collected.

Results

349 patients were included; mean age: 43.7±8.9 y, 70.5% male and 89.1% Caucasian. Main transmission categories were IVDU (36.4%) and heterosexual (36.4%). Mean time from HIV diagnosis was 11.3±7.6 y. 59.5% were CDC C category. Median CD4 nadir was: 155 cells/mm3 and median CD4 at the time of switching was 467 cells/mm3. 64.1% had undetectable viral load (<50 copies/ml); 40.1% had HCV or HBV co‐infection. Main reasons for treatment change were simplification (40.2%), treatment toxicities (29.2%) and immune/viral failure (20.1%). No significant correlations were found between reason for changing treatment and age, gender, race, nationality and level of education. Simplification was significantly the main reason both in employed and unemployed patients (p<0.01).

Conclusions

Currently, treatment simplification was the most prevalent reason for a change of treatment even in advanced lines of treatment. This is so probably because of the advent of ARV drugs that are more potent and effective, with less toxicity and more convenient. Treatment simplification was significantly the first cause of treatment change in those patients who are currently working or seeking for a job. This highlights the need for simpler regimens that can adapt to an active life.
Switch from efavirenz to nevirapine, with full dose after one week: efficacy, safety and pharmacokinetics
Authors: Curran A , Crespo M , van den Eynde E , Perez M , Burgos J , Navarro J , Falcó V , Villar del Saz S , Ocaña I , Ribera E
Published: November 2012

Purpose of the study

In a prior study in patients switching from efavirenz (EFV) due to neurologic side effects, we compared nevirapine (NVP) full dose (200 mg twice‐daily) from the beginning to the standard dosage (200 mg once‐daily for two weeks and then increase to 200 mg twice‐daily) [1]. Adequate concentrations were seen with the experimental arm but with a trend towards higher toxicity, with 25% of patients having to stop NVP due to rash or hepatitis. Our hypothesis is that NVP 200 mg daily for 1 week and then increasing it to 200 mg twice‐daily will achieve adequate plasmatic concentrations with better tolerability.

Methods

Patients taking an EFV‐based regimen were offered to switch to NVP without changing the backbone. Patients received NVP 200 mg once‐daily for 1 week and 200 mg twice‐daily thereafter. EFV and NVP plasma trough levels were determined at days 0, 3, 7, 14, 30 and 90. Blood tests were performed at each visit and AE recorded. Chi‐squared and Fisher exact test were used for qualitative variables and Mann‐Whitney U and Wilcoxon signed rank tests for quantitative variables.

Summary of results

22 patients were included, 73% male, median age 48 years, median CD4 569 cell/mm3, all with CV <25 copies/mL and 41% had HCV co‐infection. Reasons for switch were CNS symptoms in 50%, dyslipidemia in 46% and pregnancy desire in 4%. Backbone was TDF+FTC in 73% and ABC+3TC in 27%. Median NVP trough concentrations were 2.2, 2.7, 4.3, 4.5 and 5.5 µg/mL at 3, 7, 14, 30 and 90 days, respectively. 35% of patients had NVP plasma trough levels >3 µg/mL at day 7 and 88% at day 14. EFV concentrations were subtherapeutic (<1 µg/mL) at day 7 and undetectable in all but one patient at day 14. There was a significant increase in GGT (+22 mg/dL, p=.013) and significant decreases in total cholesterol (−16 mg/dL, p=.035) and triglycerides (−50 mg/dL, p=.005) after 3 months. In the first month, two patients had to stop NVP due to rash and one due to rash and hepatitis. There was no correlation between plasma concentrations and rash or hepatitis. There were no virologic failures.

Conclusions

Nevirapine concentrations were adequate when dose was increased to 200 mg twice daily after one week, maintaining virologic efficacy and with good tolerability.
Nanostructured Crystalline Comb Polymer of Perylenebisimide by Directed Self‐Assembly: Poly(4‐vinylpyridine)‐pentadecylphenol Perylenebisimide
Authors: Narayan Rekha , Kumar Prashant , Narayan K. S. , Asha S. K.
Published: November 2012

Well defined nanostructured polymeric supramolecular assemblies are formed when an asymmetric perylenebisimide substituted with ethylhexyl chains on one end and functionalized with 3‐pentadecylphenol at the other termini (PDP‐UPBI) is complexed with poly(4‐vinylpyridine) (P4VP) via a non‐covalent specific interaction such as hydrogen‐bonding. The resulting P4VP(PDP‐UPBI)n complexes are fully solution processable. The bulk structure and morphologies of the supramolecular film studied using small angle and wide angle X‐ray scattering reveals highly crystalline nature of the complex. Thin film morphology of the 1:1 complex analyzed using transmission electron microscopy shows uniform lamellar structures in the domain range of 5–10 nm. A clear trend of improved electrical parameters in P4VP(PDP‐UPBI) system compared to pristine (PDP‐UPBI) is observed from space charge limited current measurements. In short, a simple and facile method to obtain spatially defined organization of n‐type semiconductor perylenebisimide molecules using hydrogen bonding interactions with P4VP as the structural motif is showcased herein.
Metal Nanocrystal‐Embedded Hollow Mesoporous TiO2 and ZrO2 Microspheres Prepared with Polystyrene Nanospheres as Carriers and Templates
Authors: Jin Zhao , Wang Feng , Wang Feng , Wang Junxin , Yu Jimmy C. , Wang Jianfang
Published: November 2012

Noble metal nanocrystals with different shapes and compositions are embedded in hollow mesoporous metal oxide microspheres through an ultrasonic aerosol spray. Polystyrene (PS) nanospheres are employed simultaneously as a hard template to create hollow interiors inside the oxide microspheres and as the carrier to bring pregrown metal nanocrystals, including Pd nanocubes, Au nanorods, and Au core/Pd shell nanorods, into the oxide microspheres. Calcination removes the PS template and causes the metal nanocrystals to adsorb on the inner surface of the hollow oxide microspheres. The catalytic performances of the Pd nanocube‐embedded TiO2 and ZrO2 microspheres are investigated using the reduction of 4‐nitrophenol as a model reaction. The presence of the mesopores in the oxide microspheres allows the reactant molecules to diffuse into the hollow interiors and subsequently interact with the Pd nanocubes. The embedding of the metal nanocrystals in the hollow oxide microspheres prevents the aggregation of the metal nanocrystals and reduces the loss of the catalyst during recycling. The Pd nanocube‐embedded ZrO2 microspheres are found to exhibit a much higher catalytic activity, a much larger catalytic reaction rate, and a superior recyclability in comparison with a commercial Pd/C catalyst. This preparation approach could potentially be utilized to incorporate various types of mono‐ and multimetallic nanocrystals with different sizes, shapes, and compositions into hollow mesoporous oxide microspheres. Such a capability can facilitate the studies of the catalytic properties of various combinations of metal nanocrystals and metal oxide supports and therefore guide the design and creation of high‐performance catalysts.
Membrane‐Directed High Bactericidal Activity of (Gold Nanoparticle)–Polythiophene Composite for Niche Applications Against Pathogenic Bacteria
Authors: Adhikari Manab Deb , Goswami Sudeep , Panda Biswa Ranjan , Chattopadhyay Arun , Ramesh Aiyagari
Published: November 2012

The use of nanoscale materials as bactericidal agents represents a novel paradigm in the development of therapeutics against drug‐resistant pathogenic bacteria. In this paper the antimicrobial activity of a water soluble (gold nanoparticle)–polythiophene (AuNP‐PTh) composite against common bacterial pathogens is reported. The nanocomposite is broad‐spectrum in its bactericidal activity and exhibits a membrane‐directed mode of action on target pathogens. The therapeutic potency of AuNP‐PTh is demonstrated by experiments which reveal that the nanocomposite can breach the outer membrane defense barrier of Gram‐negative pathogens for subsequent killing by a hydrophobic antibiotic, inhibit the growth of model gastrointestinal pathogens in simulated gastric fluid, and significantly eradicate bacterial biofilms. The high bacterial selectivity and lack of cytotoxicity on human cells augers well for future therapeutic application of the nanocomposite against clinically relevant pathogenic bacteria.