Displaying publications 1 - 20 of 43 in total

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  1. Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott JH, et al.
    AIDS, 2016 09 10;30(14):2159-68.
    PMID: 27281059 DOI: 10.1097/QAD.0000000000001179
    BACKGROUND: Chronic HIV infection leads to marked depletion of CD4 T cells in the gastrointestinal tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor 4 (TLR4) and CD14, the principal receptors for LPS, were associated with CD4 T-cell recovery postantiretroviral therapy (ART).

    METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models.

    RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P 

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  2. Rajasuriar R, Chong ML, Ahmad Bashah NS, Abdul Aziz SA, Mcstea M, Lee ECY, et al.
    AIDS, 2017 06 19;31(10):1393-1403.
    PMID: 28358731 DOI: 10.1097/QAD.0000000000001475
    BACKGROUND: Aging among HIV-infected individuals on antiretroviral therapy (ART) is a significant clinical challenge; however, studies assessing multidimensional aspects of aging are lacking. We characterized 10 geriatric conditions encompassing multiple functional domains, its health impact and associated risk factors in HIV-infected and age-matched uninfected controls.

    METHODS: HIV-infected individuals were recruited from the outpatient clinic in University Malaya Medical Centre, Malaysia and controls from the community. All participants were aged at least 25 years of age with no acute illness, and HIV-infected individuals were on stable ART. Geriatric conditions were assessed and the burden scored as a composite of geriatric conditions present in an individual (total score = 10). Multivariate regression analysis was performed to determine the risk factors and health impact associated with the burden of geriatric conditions.

    RESULTS: We analyzed data from 336 HIV-infected individuals (total HIV+), of whom 172 were matched for age, sex, and ethnicity with 172 HIV-uninfected controls (matched subset). In the total HIV-positive cohort, median (interquartile range) age was 44 (38-51) years and CD4 T-cell count was 562 (398-737) cells/μl. The burden of geriatric conditions was significantly higher in the HIV-infected group compared with controls (P 
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  3. Che Pa MF, Makmor-Bakry M, Islahudin F
    AIDS Patient Care STDS, 2023 Nov;37(11):507-516.
    PMID: 37956244 DOI: 10.1089/apc.2023.0170
    Adherence to antiretroviral therapy (ART) is essential in determining successful treatment of human immunodeficiency virus (HIV). The adoption of digital health is suggested to improve ART adherence among people living with HIV (PLHIV). This study aimed to systematically determine the effect of digital health in enhancing ART adherence among PLHIV from published studies. The systematic search was conducted on Scopus, Web of Science (WoS), PubMed, Ovid, EBSCOHost, and Google Scholar databases up to June 2022. Studies utilized any digital health as an intervention for ART adherence enhancement and ART adherence status as study's outcome was included. Digital health refers to the use of information and communication technologies to improve health. Quality assessment and data analysis were carried out using Review Manager (RevMan) version 5.4. A random-effects model computed the pooled odds ratio between intervention and control groups. The search produced a total of 1864 articles. Eleven articles were eligible for analysis. Digital health was used as follows: six studies used short message service or text message alone, three studies used mobile applications, and two studies used combination method. Four studies showed statistically significant impacts of digital health on ART adherence, while seven studies reported insignificant results. Results showed studies conducted using combination approach of digital health produced more promising outcome in ART adherence compared to single approach. New innovative in combination ways is required to address potential benefits of digital health in promoting ART adherence among PLHIV.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  4. Lam EP, Moore CL, Gotuzzo E, Nwizu C, Kamarulzaman A, Chetchotisakd P, et al.
    AIDS Res Hum Retroviruses, 2016 09;32(9):841-50.
    PMID: 27346600 DOI: 10.1089/AID.2015.0331
    We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p  .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p 
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  5. Meyer JP, Zelenev A, Wickersham JA, Williams CT, Teixeira PA, Altice FL
    Am J Public Health, 2014 Mar;104(3):434-41.
    PMID: 24432878 DOI: 10.2105/AJPH.2013.301553
    We assessed gender differences in longitudinal HIV treatment outcomes among HIV-infected jail detainees transitioning to the community.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  6. HIV-CAUSAL Collaboration, Cain LE, Logan R, Robins JM, Sterne JA, Sabin C, et al.
    Ann Intern Med, 2011 Apr 19;154(8):509-15.
    PMID: 21502648 DOI: 10.7326/0003-4819-154-8-201104190-00001
    BACKGROUND: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.

    OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated.

    DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.

    SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States.

    PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis.

    MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.

    RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.

    LIMITATIONS: CD4 cell count at cART initiation was not randomized. Residual confounding may exist.

    CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  7. Jaafar J, Hitam WH, Noor RA
    Asian Pac J Trop Biomed, 2012 Jul;2(7):586-8.
    PMID: 23569976 DOI: 10.1016/S2221-1691(12)60102-6
    A 27 year-old lady, presented with sudden loss of vision in the right eye for a week. It was followed by poor vision in the left eye after 3 days. It involved the whole entire visual field and was associated with pain on eye movement. She was diagnosed to have miliary tuberculosis and retroviral disease 4 months ago. She was started on anti-TB since then but defaulted highly active anti-retroviral therapy (HAART). On examination, her visual acuity was no perception of light in the right eye and 6/120 (pinhole 3/60) in the left eye. Anterior segment in both eyes was unremarkable. Funduscopy showed bilateral optic disc swelling with presence of multiple foci of choroiditis in the peripheral retina. The vitreous and retinal vessels were normal. Chest radiography was normal. CT scan of orbit and brain revealed bilateral enhancement of the optic nerve sheath that suggest the diagnosis of bilateral atypical optic neuritis. This patient was managed with infectious disease team. She was started on HAART and anti-TB treatment was continued. She completed anti-TB treatment after 9 months without any serious side effects. During follow up the visual acuity in both eyes was not improved. However, funduscopy showed resolving of disc swelling and choroiditis following treatment.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  8. Chatha ZF, Rashid U, Olsen S, Din FU, Khan A, Nawaz K, et al.
    BMC Infect Dis, 2020 Nov 23;20(1):874.
    PMID: 33228562 DOI: 10.1186/s12879-020-05571-w
    BACKGROUND: Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH).

    METHODS: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire.

    RESULTS: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p 

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  9. Tan DB, Yong YK, Tan HY, Kamarulzaman A, Tan LH, Lim A, et al.
    HIV Med, 2008 May;9(5):307-16.
    PMID: 18400078 DOI: 10.1111/j.1468-1293.2008.00565.x
    A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  10. Bijker R, Jiamsakul A, Uy E, Kumarasamy N, Ditango R, Chaiwarith R, et al.
    HIV Med, 2019 03;20(3):183-191.
    PMID: 30620108 DOI: 10.1111/hiv.12687
    OBJECTIVES: With aging of the HIV-positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD-related and other causes of death (CODs) and factors associated with CVD in a multi-country Asian HIV-positive cohort.

    METHODS: Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD.

    RESULTS: Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries.

    CONCLUSIONS: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  11. Leng CY, Low HC, Chua LL, Chong ML, Sulaiman H, Azwa I, et al.
    HIV Med, 2017 05;18(5):321-331.
    PMID: 27649852 DOI: 10.1111/hiv.12432
    OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.

    METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.

    RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.

    CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  12. Meyer JP, Cepeda J, Wu J, Trestman RL, Altice FL, Springer SA
    JAMA Intern Med, 2014 May;174(5):721-9.
    PMID: 24687044 DOI: 10.1001/jamainternmed.2014.601
    Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  13. Phanuphak P, Sirivichayakul S, Jiamsakul A, Sungkanuparph S, Kumarasamy N, Lee MP, et al.
    J Acquir Immune Defic Syndr, 2014 May 01;66(1):74-9.
    PMID: 24413039 DOI: 10.1097/QAI.0000000000000108
    BACKGROUND: We compared treatment outcomes of transmitted drug resistance (TDR) in patients on fully or partially sensitive drug regimens.

    METHODS: Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models.

    RESULTS: TDR, found in 60 (4.1%) of 1471 Asian treatment-naive patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR.

    CONCLUSIONS: TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  14. Bartlett AW, Lumbiganon P, Jamal Mohamed TA, Lapphra K, Muktiarti D, Du QT, et al.
    J Acquir Immune Defic Syndr, 2019 12 15;82(5):431-438.
    PMID: 31714422 DOI: 10.1097/QAI.0000000000002184
    BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.

    SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

    METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

    RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.

    CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  15. Ross JL, Teeraananchai S, Lumbiganon P, Hansudewechakul R, Chokephaibulkit K, Khanh TH, et al.
    J Acquir Immune Defic Syndr, 2019 06 01;81(2):e28-e38.
    PMID: 30865173 DOI: 10.1097/QAI.0000000000002008
    BACKGROUND: Adolescents living with HIV (ALHIV) have poorer adherence and clinical outcomes than adults. We conducted a study to assess behavioral risks and antiretroviral therapy outcomes among ALHIV in Asia.

    METHODS: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12-18 years was conducted at 9 sites in Malaysia, Thailand, and Vietnam from July 2013 to March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96, and 144. Virologic failure (VF) was defined as ≥1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF.

    RESULTS: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% females. The median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (P < 0.01); similar proportions of ALHIV and controls drank alcohol (58% vs. 65%), used inhalants (1% vs. 2%), had been sexually active (31% vs. 21%), and consistently used condoms (42% vs. 44%). Of the 73% of ALHIV with week 144 VL testing, median log VL was 1.60 (interquartile range 1.30-1.70) and 19% had VF. Over 70% of ALHIV had not disclosed their HIV status. Self-reported adherence ≥95% was 60% at week 144. Smoking cigarettes, >1 sexual partner, and living with nonparent relatives, a partner or alone, were associated with VF at any time.

    CONCLUSIONS: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  16. Boettiger DC, Nguyen VK, Durier N, Bui HV, Heng Sim BL, Azwa I, et al.
    J Acquir Immune Defic Syndr, 2015 Feb 01;68(2):186-95.
    PMID: 25590271 DOI: 10.1097/QAI.0000000000000411
    BACKGROUND: Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources, it is important to optimize the timing of second-line ART initiation and use the most effective compounds available.

    METHODS: HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated.

    RESULTS: There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure.

    CONCLUSIONS: Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use*
  17. Pham MD, Haile BA, Azwa I, Kamarulzaman A, Raman N, Saeidi A, et al.
    J Clin Microbiol, 2019 04;57(4).
    PMID: 30700508 DOI: 10.1128/JCM.01683-18
    HIV viral load (VL) testing is the recommended method for monitoring the response of people living with HIV and receiving antiretroviral therapy (ART). The availability of standard plasma VL testing in low- and middle-income countries (LMICs), and access to this testing, are limited by the need to use fresh plasma. Good specimen collection methods for HIV VL testing that are applicable to resource-constrained settings are needed. We assessed the diagnostic performance of the filtered dried plasma spot (FDPS), created using the newly developed, instrument-free VLPlasma device, in identifying treatment failure at a VL threshold of 1,000 copies/ml in fresh plasma. Performance was compared with that of the conventional dried blood spot (DBS). Venous blood samples from 201 people living with HIV and attending an infectious disease clinic in Malaysia were collected, and HIV VL was quantified using fresh plasma (the reference standard), FDPS, and DBS specimens. VL testing was done using the Roche Cobas AmpliPrep/Cobas TaqMan v2.0 assay. At a threshold of 1,000 copies/ml, the diagnostic performance of the FDPS was superior (sensitivity, 100% [95% confidence interval {CI}, 89.1 to 100%]; specificity, 100% [95% CI, 97.8 to 100%]) to that of the DBS (sensitivity, 100% [95% CI, 89.4 to 100%]; specificity, 36.8% [95% CI, 29.4 to 44.7%]) (P 
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  18. Ahmed A, Dujaili J, Sandhu AK, Hashmi FK
    J Glob Health, 2020 Dec;10(2):020342.
    PMID: 33110542 DOI: 10.7189/jogh.10.020342
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  19. Tan HY, Yong YK, Shankar EM, Paukovics G, Ellegård R, Larsson M, et al.
    J Immunol, 2016 05 15;196(10):4052-63.
    PMID: 27076678 DOI: 10.4049/jimmunol.1502203
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
  20. Fahrni ML, Misran NFL, Abidin ZZ, Chidambaram SK, Lazzarino AI
    J Infect Public Health, 2023 Jan;16(1):96-103.
    PMID: 36508946 DOI: 10.1016/j.jiph.2022.12.001
    BACKGROUND: While efavirenz-associated adverse drug events (ADEs) were widely established, the clinical relevance is uncertain.

    OBJECTIVES: We aimed to assess the extent of treatment interruption caused by efavirenz-associated ADEs.

    METHODS: A case-control study of efavirenz recipients who did, versus did not (control) develop adverse drug events (ADE), and who were matched for baseline CD4 + at a ratio of 1:1.3 was conducted. Antiretroviral -naïve patients who were started on efavirenz were followed up retrospectively, and their records scrutinized every month for 2 years. Demographic and clinical predictors of treatment interruption were computed using Cox proportional hazard models. Kaplan- Meier curves were plotted to assess time to treatment interruption for the two groups. Clinical endpoints were: i) efficacy -improved CD4 + counts and/or viral load (VL) suppression, ii) safety -absence of treatment-limiting toxicities, and iii) durability - no interruption until follow-up ended.

    RESULTS: Both groups had comparable CD4 + counts at baseline (p = 0.15). At t = 24-months, VL in both groups were suppressed to undetectable levels (<20 copies/mL) while median CD4 + was 353 cells/µL (IQR: 249-460). The mean time on treatment was 23 months (95% CI, 22.3 -23.4) in the control group without ADE and 20 months (95% CI, 18.9 - 21.6) in the ADE group (p = 0.001). Kaplan-Meier plots demonstrated that 59.5% of patients who experienced ≥ 1 ADE versus 81% of those who did not experience any ADE were estimated to continue treatment for up to 24 months with no interruption (p = 0.001). Most interruptions to EFV treatment occurred in the presence of opportunistic infections and these were detected within the first 5 months of treatment initiation. Independent predictors which negatively impacted the dependent variable i.e., treatment durability, were intravenous drug use (adjusted hazard ratio, aHR 2.17, 95% CI, 1.03-4.61, p = 0.043), presence of ≥ 1 opportunistic infection(s) (aHR 2.2, 95% CI, 1.13-4.21, p = 0.021), and presence of ≥ 1 serious ADE(s) (aHR 4.18, 95% CI, 1.98-8.85, p = 0.00).

    CONCLUSION: Efavirenz' role as the preferred first-line regimen for South-East Asia's resource-limited regions will need to be carefully tailored to suit the regional population. Findings have implications to policy-makers and clinicians, particularly for the treatment of patients who develop ADEs and opportunistic infections, and for intravenous drug user subgroups.

    Matched MeSH terms: Anti-Retroviral Agents/therapeutic use
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