Displaying all 14 publications

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  1. López M
    AIDS Rev, 2013 Jul-Sep;15(3):190-1.
    PMID: 24002204
    The 7th IAS Conference held in July 2013 in Kuala Lumpur, Malaysia, heard about a number of cases of "functional cure" in people who had started antiretroviral therapy soon after HIV infection, including a German case that can now be added to the "Mississippi baby" report presented at CROI 2012 and 14 individuals of the French VISCONTI cohort. All these persons maintained an undetectable viral load after coming off antiretrovirals.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*
  2. AIDS Patient Care STDS, 2000 Apr;14(4):225-6.
    PMID: 10806645
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*
  3. Rabasseda X
    Drugs Today, 2013 Aug;49(8):509-17.
    PMID: 23977668 DOI: 10.1358/dot.2013.49.8.2033100
    Effective antiretroviral drugs have been developed that, if continuously administered (although with simplification strategies once a patient's viral titer is suppressed) allow for a functional cure resulting in an almost normal life despite the presence of viral reservoirs. In that sense, observations that combination antiretroviral therapy has an untoward suppressive effect on antibody-dependent cellular cytotoxicity against T cells permitting the establishment of such viral reservoirs were discussed for its implications in the use of vaccines and/or modulators of the immune function to clear latent infections and the risk for reactivation (Madhavi, V. et al., Abst MOLBPE05). In addition to latent viral reservoirs, individual patient characteristics may also influence response to antiretroviral therapy, as exemplified by the increased likelihood of highly active antiretroviral therapy in patients carrying certain polymorphic variants (rs2229109, rs6961419) of the P-glycoprotein 1 gene (Dias, J. et al., Abst MOPE034). These, and many other important news derived from research into novel approaches to fight HIV infection were discussed during the International AIDS Society (IAS) meeting in Kuala Lumpur, as summarized in the following report.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  4. Xu ZQ, Norris KJ, Weinberg DS, Kardatzke J, Wertz P, Frank P, et al.
    J. Chromatogr. B Biomed. Sci. Appl., 2000 Jun 09;742(2):267-75.
    PMID: 10901131
    A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  5. Ahn JY, Boettiger D, Law M, Kumarasamy N, Yunihastuti E, Chaiwarith R, et al.
    J. Acquir. Immune Defic. Syndr., 2015 Jul 1;69(3):e85-92.
    PMID: 25850606 DOI: 10.1097/QAI.0000000000000634
    Current treatment guidelines for HIV infection recommend routine CD4 lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*
  6. Ku NS, Jiamsakul A, Ng OT, Yunihastuti E, Cuong do D, Lee MP, et al.
    Medicine (Baltimore), 2016 Aug;95(32):e4570.
    PMID: 27512885 DOI: 10.1097/MD.0000000000004570
    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  7. Jiamsakul A, Kerr SJ, Ng OT, Lee MP, Chaiwarith R, Yunihastuti E, et al.
    Trop. Med. Int. Health, 2016 May;21(5):662-74.
    PMID: 26950901 DOI: 10.1111/tmi.12690
    OBJECTIVES: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.

    METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.

    RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).

    CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

    Matched MeSH terms: Anti-HIV Agents/administration & dosage*
  8. Chow WZ, Lim SH, Ong LY, Yong YK, Takebe Y, Kamarulzaman A, et al.
    PLoS ONE, 2015;10(9):e0137281.
    PMID: 26335136 DOI: 10.1371/journal.pone.0137281
    Human immunodeficiency virus type 1 (HIV-1) subtypes have been shown to differ in the rate of clinical progression. We studied the association between HIV-1 subtypes and the rate of CD4+ T-cell recovery in a longitudinal cohort of patients on combination antiretroviral therapy (cART). We studied 103 patients infected with CRF01_AE (69%) and subtype B (31%) who initiated cART between 2006 and 2013. Demographic data, CD4+ T-cell counts and HIV-1 viral load were abstracted from patient medical charts. Kaplan-Meier was used to estimate the time to CD4+ T-cell count increase to ≥350 between subtypes and effects of covariates were analysed using Cox proportional hazards. An 87% of the study population were male adults (mean age of 38.7 years old). Baseline CD4+ T-cell counts and viral loads, age at cART initiation, sex, ethnicity and co-infection did not differ significantly between subtypes. A shorter median time for CD4+ T-cell count increase to ≥350 cells/μL was observed for CRF01_AE (546 days; 95% confidence interval [CI], 186-906 days; P = .502) compared to subtype B (987 days; 95% CI, 894-1079 days). In multivariate analysis, female sex was significantly associated with a 2.7 times higher chance of achieving CD4+ T-cell recovery (adjusted hazard ratio [HR], 2.75; 95% CI, 1.21-6.22; P = .025) and both baseline CD4+ T-cell count (P = .001) and viral load (P = .001) were important predictors for CD4+ T-cell recovery. Immunological recovery correlated significantly with female sex, baseline CD4+ T-cell counts and viral load but not subtype.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  9. Razali SM
    Trop Doct, 2008 Apr;38(2):109-10.
    PMID: 18453507 DOI: 10.1258/td.2007.070001
    The prevalence of HIV/AIDS among drug addicts in Malaysia is high, especially among intravenous drug users. The present treatment and rehabilitation of drug addiction is considered as a failure. The government finally decided to start on Drug Substitution Therapy in early 2005 as an effort to prevent the spread of HIV/AIDS in the country.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  10. Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.
    Sci Rep, 2018 09 24;8(1):14277.
    PMID: 30250162 DOI: 10.1038/s41598-018-32585-x
    We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  11. Kamarulzaman A, Altice FL
    Curr. Opin. Infect. Dis., 2015 Feb;28(1):10-6.
    PMID: 25490106 DOI: 10.1097/QCO.0000000000000125
    HIV management in people who use drugs (PWUD) is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care. In this review, we describe the individual, health systems and societal barriers to HIV treatment access and care retention for PWUD. In addition, the clinical management of HIV-infected PWUD is often complicated by the presence of multiple infectious and noninfectious comorbidities.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*
  12. Moy FS, Fahey P, Nik Yusoff NK, Razali KA, Nallusamy R, TREAT Asia Pediatric HIV Observational Database (TApHOD)
    J Paediatr Child Health, 2015 Feb;51(2):204-8.
    PMID: 25142757 DOI: 10.1111/jpc.12712
    To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART).
    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  13. Joshi K, Boettiger D, Kerr S, Nishijima T, Van Nguyen K, Ly PS, et al.
    Pharmacoepidemiol Drug Saf, 2018 11;27(11):1209-1216.
    PMID: 30246898 DOI: 10.1002/pds.4657
    PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia.

    METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).

    RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.

    CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

    Matched MeSH terms: Anti-HIV Agents/administration & dosage
  14. Boyd MA, Amin J, Mallon PW, Kumarasamy N, Lombaard J, Wood R, et al.
    Lancet HIV, 2017 01;4(1):e13-e20.
    PMID: 27815068 DOI: 10.1016/S2352-3018(16)30189-8
    BACKGROUND: Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir.

    METHODS: Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.

    FINDINGS: Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).

    INTERPRETATION: Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.

    FUNDING: The Kirby Institute and the Australian National Health and Medical Research Council.

    Matched MeSH terms: Anti-HIV Agents/administration & dosage
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