Displaying publications 1 - 20 of 137 in total

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  1. Sukeepaisarnjaroen W, Pham T, Tanwandee T, Nazareth S, Galhenage S, Mollison L, et al.
    World J Gastroenterol, 2015 Jul 28;21(28):8660-9.
    PMID: 26229408 DOI: 10.3748/wjg.v21.i28.8660
    To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia.
    Matched MeSH terms: Viral Load
  2. Yun SI, Song BH, Frank JC, Julander JG, Olsen AL, Polejaeva IA, et al.
    Viruses, 2018 08 11;10(8).
    PMID: 30103523 DOI: 10.3390/v10080422
    Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously undescribed gene products identified in the case of all three molecularly cloned ZIKVs. (ii) We found that ZIKV has a broad cell tropism in vitro, being capable of establishing productive infection in 16 of 17 animal cell lines from 12 different species, although its growth kinetics varied depending on both the specific virus strain and host cell line. More importantly, we identified one ZIKV-non-susceptible bovine cell line that has a block in viral entry but fully supports the subsequent post-entry steps. (iii) We showed that in mice, the three molecularly cloned ZIKVs differ in their neuropathogenicity, depending on the particular combination of viral and host genetic backgrounds, as well as in the presence or absence of type I/II interferon signaling. Overall, our findings demonstrate the impact of viral and host genetic variations on the replication kinetics and neuropathogenicity of ZIKV and provide multiple avenues for developing and testing medical countermeasures against ZIKV.
    Matched MeSH terms: Viral Load
  3. Yee PTI, Mohamed RAH, Ong SK, Tan KO, Poh CL
    Virus Res, 2017 06 15;238:243-252.
    PMID: 28705680 DOI: 10.1016/j.virusres.2017.07.010
    One of the leading causes of the hand, foot and mouth disease (HFMD) is Enterovirus 71 (EV-A71), displaying symptoms such as fever and ulcers in children but some strains can produce cardiopulmonary oedema which leads to death. There is no FDA-approved vaccine for prevention of severe HFMD. The molecular determinants of virulence for EV-A71 are unclear. It could be a single or a combination of amino acids that determines virulence in different EV-A71 genotype/sub-genotypes. Several EV-A71 strains bearing single nucleotide (nt) mutations were constructed and the contribution of each mutation to virulence was evaluated. The nt(s) that contributed to significant reduction in virulence in vitro were selected and each mutation was introduced separately into the genome to construct the multiply mutated EV-A71 strain (MMS) which carried six substitutions of nt(s) at the 5'-NTR (U700C), VP1-145 (E to G), VP1-98E, VP1-244K and G64R in the vaccine seed strain that had a partial deletion within the 5'-NTR region (nt. 475-485) of Δ11bp. In comparison to the wild type strain, the MMS showed low virulence as it produced very low RNA copy number, plaque count, VP1 and had 105-fold higher TCID50, indicative of a promising LAV candidate that should be further evaluated in vivo.
    Matched MeSH terms: Viral Load
  4. Mehrbod P, Ideris A, Omar AR, Hair-Bejo M, Tan SW, Kheiri MT, et al.
    Virol J, 2012;9:44.
    PMID: 22340010 DOI: 10.1186/1743-422X-9-44
    The influenza virus is still one of the most important respiratory risks affecting humans which require effective treatments. In this case, traditional medications are of interest. HESA-A is an active natural biological compound from herbal-marine origin. Previous studies have reported that the therapeutic properties of HESA-A are able to treat psoriasis vulgaris and cancers. However, no antiviral properties have been reported.
    Matched MeSH terms: Viral Load
  5. Oong XY, Chook JB, Ng KT, Chow WZ, Chan KG, Hanafi NS, et al.
    Virol J, 2018 05 23;15(1):91.
    PMID: 29792212 DOI: 10.1186/s12985-018-1005-8
    BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections.
    METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses.
    RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3-5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log10 RNA copies/μl) (p = 0.003).
    CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission.
    Study site: Primary Care Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Viral Load
  6. Abdul Ahmad SA, Palanisamy UD, Khoo JJ, Dhanoa A, Syed Hassan S
    Virol J, 2019 02 27;16(1):26.
    PMID: 30813954 DOI: 10.1186/s12985-019-1127-7
    BACKGROUND: Dengue continues to be a major international public health concern. Despite that, there is no clinically approved antiviral for treatment of dengue virus (DENV) infections. In this study, geraniin extracted from the rind of Nephelium lappaceum was shown to inhibit the replication of DENV-2 in both in vitro and in vivo experiments.

    METHODS: The effect of geraniin on DENV-2 RNA synthesis in infected Vero cells was tested using quantitative RT-PCR. The in vivo efficacy of geraniin in inhibiting DENV-2 infection was then tested using BALB/c mice with geraniin administered at three different times. The differences in spleen to body weight ratio, DENV-2 RNA load and liver damage between the three treatment groups as compared to DENV-2 infected mice without geraniin administration were determined on day eight post-infection.

    RESULTS: Quantitative RT-PCR confirmed the decrease in viral RNA synthesis of infected Vero cells when treated with geraniin. Geraniin seemed to provide a protective effect on infected BALB/c mice liver when given at 24 h pre- and 24 h post-infection as liver damage was observed to be very mild even though a significant reduction of DENV-2 RNA load in serum was not observed in these two treatment groups. However, when administered at 72 h post-infection, severe liver damage in the form of necrosis and haemorrhage had prevailed despite a substantial reduction of DENV-2 RNA load in serum.

    CONCLUSIONS: Geraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h post-infection while earlier administration could prevent severe liver damage caused by DENV-2 infection. These results provide evidence that geraniin is a potential candidate for the development of anti-dengue drug.

    Matched MeSH terms: Viral Load
  7. Capozza P, Lorusso E, Colella V, Thibault JC, Tan DY, Tronel JP, et al.
    Vet Microbiol, 2021 Mar;254:109008.
    PMID: 33582484 DOI: 10.1016/j.vetmic.2021.109008
    Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in cats with infection in its progressive form. Although there are numerous reports on the occurrence of FeLV in the feline population worldwide, there is a paucity of data in Asia. In this study, we assessed the circulation of FeLV by ELISA and nested PCR in cats from different countries in Southeast Asia (i.e., Thailand, Malaysia, Singapore, Philippines, Indonesia and Vietnam) and Taiwan during 2017-2018. Forty-seven cats were positive to FeLV by antigen or provirus detection, but 32 samples were considered truly positive on the basis of positive molecular testing. Frequency of occurrence of FeLV proviral DNA ranged from 0% (0/43 positive samples) in Indonesia to 18.5% (22/119 positive samples) in Thailand. A statistically significant association (p < 0.05) was found between country of cats origin, age, lifestyle, abnormal oral mucosa, and FeLV molecular positive results. In-depth studies are needed in other countries in Southeast Asia to elucidate the mosaic of knowledge about FeLV epidemiology.
    Matched MeSH terms: Viral Load
  8. Lei W, Guo X, Fu S, Feng Y, Tao X, Gao X, et al.
    Vet Microbiol, 2017 Mar;201:32-41.
    PMID: 28284620 DOI: 10.1016/j.vetmic.2017.01.003
    BACKGROUND: Since the turn of the 21st century, there have been several epidemic outbreaks of poultry diseases caused by Tembusu virus (TMUV). Although multiple mosquito and poultry-derived strains of TMUV have been isolated, no data exist about their comparative study, origin, evolution, and dissemination.

    METHODOLOGY: Parallel virology was used to investigate the phenotypes of duck and mosquito-derived isolates of TMUV. Molecular biology and bioinformatics methods were employed to investigate the genetic characteristics and evolution of TMUV.

    PRINCIPAL FINDINGS: The plaque diameter of duck-derived isolates of TMUV was larger than that of mosquito-derived isolates. The cytopathic effect (CPE) in mammalian cells occurred more rapidly induced by duck-derived isolates than by mosquito-derived isolates. Furthermore, duck-derived isolates required less time to reach maximum titer, and exhibited higher viral titer. These findings suggested that poultry-derived TMUV isolates were more invasive and had greater expansion capability than the mosquito-derived isolates in mammalian cells. Variations in amino acid loci in TMUV E gene sequence revealed two mutated amino acid loci in strains isolated from Malaysia, Thailand, and Chinese mainland compared with the prototypical strain of the virus (MM1775). Furthermore, TMUV isolates from the Chinese mainland had six common variations in the E gene loci that differed from the Southeast Asian strains. Phylogenetic analysis indicated that TMUV did not exhibit a species barrier in avian species and consisted of two lineages: the Southeast Asian and the Chinese mainland lineages. Molecular traceability studies revealed that the recent common evolutionary ancestor of TMUV might have appeared before 1934 and that Malaysia, Thailand and Shandong Province of China represent the three main sources related to TMUV spread.

    CONCLUSIONS: The current broad distribution of TMUV strains in Southeast Asia and Chinese mainland exhibited longer-range diffusion and larger-scale propagation. Therefore, in addition to China, other Asian and European countries linked to Asia have used improved measures to detect and monitor TMUV related diseases to prevent epidemics in poultry.

    Matched MeSH terms: Viral Load
  9. DeBuysscher BL, Scott D, Marzi A, Prescott J, Feldmann H
    Vaccine, 2014 May 07;32(22):2637-44.
    PMID: 24631094 DOI: 10.1016/j.vaccine.2014.02.087
    BACKGROUND: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks.

    METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.

    RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.

    CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.

    Matched MeSH terms: Viral Load
  10. 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: Viral Load
  11. Rothan HA, Buckle MJ, Ammar YA, Mohammadjavad P, Shatrah O, Noorsaadah AR, et al.
    Trop Biomed, 2013 Dec;30(4):681-90.
    PMID: 24522138
    Various clinical symptoms are caused by dengue virus ranging from mild fever to severe hemorrhagic fever while there is no successful anti-dengue therapeutics available. Among different strategies towards identifying and developing anti-dengue therapeutics, testing anti-dengue properties of known drugs could represent an efficient strategy for which information of its medical approval, toxicity and side effects is readily available. In this study, we evaluated the antiviral activity of some medical compounds towards dengue NS2B-NS3 protease (DENV2 NS2B-NS3pro) as a target to inhibit dengue virus replication. Mefenamic acid, a non-steroid anti inflammatory drug and doxycycline, a derivative antibiotic of tetracycline both showed significant inhibition potential against DENV2 NS2B-NS3pro Ki values 32 ± 2 μM and 55 ± 5 μM respectively. The effective cytotoxic concentrations of 50% (CC50) against Vero cells were evaluated for mefenamic acid (150 ± 5 μM) and doxycycline (125 ± 4 μM). Concentrations lower than CC50 were used to test the inhibition potential of these compounds against DENV2 replication in Vero cells. The results showed significant reduction in viral load after applying mefenamic acid and doxycyline in concentration dependent manner. Mefenamic acid reduced viral RNA at EC50 of 32 ± 4 μM whilst doxycycline EC50 was 40 ± 3 μM. Mefenamic acid showed higher selectivity against dengue virus replication in vitro compared to doxycycline. These findings underline the need for further experimental and clinical studies on these drugs utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue infection.
    Matched MeSH terms: Viral Load
  12. Ummul Haninah A, Vasan SS, Ravindran T, Chandru A, Lee HL, Shamala Devi S
    Trop Biomed, 2010 Dec;27(3):611-23.
    PMID: 21399603 MyJurnal
    This paper reports the development of a one-step SYBR-Green I-based realtime RT-PCR assay for the detection and quantification of Chikungunya virus (CHIKV) in human, monkey and mosquito samples by targeting the E1 structural gene. A preliminary evaluation of this assay has been successfully completed using 71 samples, consisting of a panel of negative control sera, sera from healthy individuals, sera from patients with acute disease from which CHIKV had been isolated, as well as monkey sera and adult mosquito samples obtained during the chikungunya fever outbreak in Malaysia in 2008. The assay was found to be 100-fold more sensitive than the conventional RT-PCR with a detection limit of 4.12x10(0) RNA copies/μl. The specificity of the assay was tested against other related viruses such as Dengue (serotypes 1-4), Japanese encephalitis, Herpes Simplex, Parainfluenza, Sindbis, Ross River, Yellow fever and West Nile viruses. The sensitivity, specificity and efficiency of this assay were 100%, 100% and 96.8% respectively. This study on early diagnostics is of importance to all endemic countries, especially Malaysia, which has been facing increasingly frequent and bigger outbreaks due to this virus since 1999.
    Matched MeSH terms: Viral Load/methods*
  13. Ellan K, Thayan R, Phan CW, Sabaratnam V
    Trop Biomed, 2019 Dec 01;36(4):1087-1098.
    PMID: 33597478
    Pathogenesis of dengue fever has been associated with the activation of the cytokine cascade that triggered inflammatory responses. The inflammatory reactions in dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) are the main cause of haemorrhagic manifestations, coagulation disorders, vascular permeability, hypotension and shock which could exacerbate the condition of the disease. In an earlier study, extracts belonging to Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune and Ganoderma lucidium mushrooms were screened for antidengue virus activities. We found that hot aqueous extract (HAE) and aqueous soluble separated from ethanol extract (ASE) exhibited their potential to reduce dengue viral load which were observed in plaque reduction assay and real-time RT-PCR. In continuation of our previous findings, this study was initiated to further investigate the other aspect; the anti-inflammatory activities of HAE and ASE of L. rhinocerotis, P. giganteus, H. erinaceus, S. commune and G. lucidium on human monocytes infected with dengue virus-2 (DENV-2) New guinea C strain. Human monocytes infected with DENV-2 were treated with mushroom extracts for 48 hours. The cytokine profile coincides with dengue infection, i.e. IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-10 were measured by BD OptEIATM Elisa Kit. The expression of these cytokines was significantly elevated in untreated infected cells two days after infection. However, after treated with mushroom extracts prominent anti-inflammatory effect were detected towards IFN-γ, IL-10, TNF-α, IL-6, and IL-1β. The most significant anti-inflammatory effects were detected in HAE of G. lucidium, S. commune, P. giganteus and ASE of L. rhinocerotis and the effects were comparable with dexamethasone, the reference inhibitor. These results demonstrated that mushroom HAE or ASE could successfully have suppressed cytokine production in dengue-infected monocytes and has a great potential to develop an antiinflammatory agent from mushroom extract for the treatment of dengue infection.
    Matched MeSH terms: Viral Load
  14. Berhane Y, Weingartl HM, Lopez J, Neufeld J, Czub S, Embury-Hyatt C, et al.
    Transbound Emerg Dis, 2008 May;55(3-4):165-74.
    PMID: 18405339 DOI: 10.1111/j.1865-1682.2008.01021.x
    Nipah virus (NiV; Paramyxoviridae) caused fatal encephalitis in humans during an outbreak in Malaysia in 1998/1999 after transmission from infected pigs. Our previous study demonstrated that the respiratory, lymphatic and central nervous systems are targets for virus replication in experimentally infected pigs. To continue the studies on pathogenesis of NiV in swine, six piglets were inoculated oronasally with 2.5 x 10(5) PFU per animal. Four pigs developed mild clinical signs, one exudative epidermitis, and one neurologic signs due to suppurative meningoencephalitis, and was euthanized at 11 days post-inoculation (dpi). Neutralizing antibodies reached in surviving animals titers around 1280 at 16 dpi. Nasal and oro-pharyngeal shedding of the NiV was detected between 2 and 17 dpi. Virus appeared to be cleared from the tissues of the infected animals by 23 dpi, with low amount of RNA detected in submandibular and bronchial lymph nodes of three pigs, and olfactory bulb of one animal. Despite the presence of neutralizing antibodies, virus was isolated from serum at 24 dpi, and the viral RNA was still detected in serum at 29 dpi. Our results indicate slower clearance of NiV from some of the infected pigs. Bacteria were detected in the cerebrospinal fluid of five NiV inoculated animals, with isolation of Streptococcus suis and Enterococcus faecalis. Staphylococcus hyicus was isolated from the skin lesions of the animal with exudative epidermitis. Along with the observed lymphoid depletion in the lymph nodes of all NiV-infected animals, and the demonstrated ability of NiV to infect porcine peripheral blood mononuclear cells in vitro, this finding warrants further investigation into a possible NiV-induced immunosuppression of the swine host.
    Matched MeSH terms: Viral Load/veterinary
  15. Lodi S, Phillips A, Logan R, Olson A, Costagliola D, Abgrall S, et al.
    Lancet HIV, 2015 Aug;2(8):e335-43.
    PMID: 26423376 DOI: 10.1016/S2352-3018(15)00108-3
    BACKGROUND: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.

    METHODS: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.

    FINDINGS: Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).

    INTERPRETATION: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.

    FUNDING: National Institutes of Health.

    Matched MeSH terms: Viral Load
  16. 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: Viral Load
  17. Loeliger KB, Altice FL, Desai MM, Ciarleglio MM, Gallagher C, Meyer JP
    Lancet HIV, 2018 02;5(2):e96-e106.
    PMID: 29191440 DOI: 10.1016/S2352-3018(17)30209-6
    BACKGROUND: Incarceration provides an opportunity for engagement in HIV care but is associated with poor HIV treatment outcomes after release. We aimed to assess post-release linkage to HIV care (LTC) and the effect of transitional case management services.

    METHODS: To create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut, USA (2007-14), we linked administrative custody and pharmacy databases with mandatory HIV/AIDS surveillance monitoring and case management data. We examined time to LTC (defined as first viral load measurement after release) and viral suppression at LTC. We used generalised estimating equations to show predictors of LTC within 14 days and 30 days of release.

    FINDINGS: Among 3302 incarceration periods for 1350 individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14 days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301 (29%) of 1042 had detectable viral loads at LTC. Factors positively associated with LTC within 14 days of release are intermediate (31-364 days) incarceration duration (adjusted odds ratio 1·52; 95% CI 1·19-1·95), and transitional case management (1·65; 1·36-1·99), receipt of antiretroviral therapy during incarceration (1·39; 1·11-1·74), and two or more medical comorbidities (1·86; 1·48-2·36). Reincarceration (0·70; 0·56-0·88) and conditional release (0·62; 0·50-0·78) were negatively associated with LTC within 14 days. Hispanic ethnicity, bonded release, and psychiatric comorbidity were also associated with LTC within 30 days but reincarceration was not.

    INTERPRETATION: LTC after release is suboptimal but improves when inmates' medical, psychiatric, and case management needs are identified and addressed before release. People who are rapidly cycling through jail facilities are particularly vulnerable to missed linkage opportunities. The use of integrated programmes to align justice and health-care goals has great potential to improve long-term HIV treatment outcomes.

    FUNDING: US National Institutes of Health.

    Matched MeSH terms: Viral Load
  18. Han WM, Law MG, Egger M, Wools-Kaloustian K, Moore R, McGowan C, et al.
    Lancet HIV, 2021 Dec;8(12):e766-e775.
    PMID: 34856180 DOI: 10.1016/S2352-3018(21)00265-4
    BACKGROUND: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART.

    METHODS: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements.

    FINDINGS: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation.

    INTERPRETATION: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents.

    FUNDING: US National Institutes of Health.

    Matched MeSH terms: Viral Load
  19. Bartlett AW, Mohamed TJ, Sudjaritruk T, Kurniati N, Nallusamy R, Hansudewechakul R, et al.
    Pediatr Infect Dis J, 2019 03;38(3):287-292.
    PMID: 30281549 DOI: 10.1097/INF.0000000000002208
    BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic systemic infection and long-term antiretroviral therapy (ART), leaving them susceptible to morbidities associated with inflammation, immunodeficiency and drug toxicity.

    METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.

    RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.

    CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.

    Matched MeSH terms: Viral Load
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