Displaying publications 21 - 40 of 55 in total

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  1. Cale EM, Gorman J, Radakovich NA, Crooks ET, Osawa K, Tong T, et al.
    Immunity, 2017 05 16;46(5):777-791.e10.
    PMID: 28514685 DOI: 10.1016/j.immuni.2017.04.011
    Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.
    Matched MeSH terms: HIV Infections/immunology*
  2. Norazmi MN, Arifin H, Jamaruddin MA
    Immunol Cell Biol, 1995 Jun;73(3):245-8.
    PMID: 7590898
    The lymphocyte subset expressing the gamma delta T cell receptor is increased in several infectious diseases including HIV infection. In this study the expression on gamma delta lymphocytes of the T cell activation markers CD25, HLA-DR and CD38, as well as the two isoforms of CD45, namely CD45RA and CD45RO, was determined in the peripheral blood of 56 HIV-infected intravenous drug users and 34 HIV-seronegative blood donors by two-colour flow cytometry. The percentage of gamma delta lymphocytes expressing HLA-DR and CD38 was higher than those in HIV-seronegative controls (P < 0.001 and P < 0.0001, respectively). Furthermore the HLA-DR+gamma delta+ lymphocytes correlated inversely with CD4+ T lymphocyte absolute count (P < 0.02 for both). The levels of gamma delta lymphocytes expressing CD25, CD45RA and CD45RO were similar to those in HIV-seronegative controls. Activated gamma delta lymphocytes may play a role in the HIV disease process and could provide a useful marker for disease progression.
    Matched MeSH terms: HIV Infections/immunology*
  3. Norazmi MN, Suarn S
    Immunol Lett, 1994 Dec;43(3):177-82.
    PMID: 7721330
    The CD4+ T-lymphocyte absolute count (CD4ac), CD4+ T-lymphocyte percentage (CD4%) and total lymphocyte count (Løac) were assessed in HIV-seropositive intravenous drug users (IVDU) with reference to their correlation with the clinical categories A, B, and C as stipulated by the Centre of Disease Control and Prevention, USA (CDC) and with each other. It was found that while the CD4ac and Løac correlated with the clinical categories, CD4% did not. This may suggest that in our local setting, the CD4% may not necessarily be a suitable alternative marker to CD4ac as proposed by CDC. Furthermore, the CD4% of the normal subjects in this study was found to be relatively lower than the reported Caucasian levels. This may indicate that the use of the cut-off level of less than 14% as an AIDS-defining criteria may not be applicable for our HIV-seropositive IVDU. In addition, unlike the CD4ac which correlated directly with CD4% and Løac, the CD4% did not correlate with Løac. Therefore, due to the observed disparity with clinical status of patients and its possibly lower levels in our normal population, CD4% as a marker for staging HIV disease should be used with caution in our setting. Such findings may also have an impact on the use of established markers for the monitoring and classification of HIV-infected individuals in this region.
    Matched MeSH terms: HIV Infections/immunology*
  4. Swathirajan CR, Vignesh R, Pradeep A, Solomon SS, Solomon S, Balakrishnan P
    Indian J Med Microbiol, 2017 Jan-Mar;35(1):37-40.
    PMID: 28303816 DOI: 10.4103/ijmm.IJMM_16_164
    CONTEXT: Diarrhoea is one of the major complications occurring in over 90% of HIV-infected individuals in developing countries. Coccidian group of parasites, being opportunistic pathogens, have been implicated as the most common causative agents of diarrhoea among HIV-infected population.

    AIMS: The aim was to study the magnitude of parasitic diarrhoea with special context to coccidian parasitic infections in HIV-infected individuals and their association with the patient's immunological status measured by CD4 T-cell counts.

    SETTINGS AND DESIGN: This investigation was performed between January 2002 and December 2014 at a tertiary HIV care centre in Chennai, South India.

    MATERIALS AND METHODS: Stool samples were collected and microscopically observed for parasites using direct, formal-ether-concentrated wet mounts and modified acid-fast staining for coccidian parasites. CD4 T-cell counts were done by FACScount.

    STATISTICAL ANALYSIS USED: All statistical analyses were performed using GraphPad Prism software, version 5.0, andP < 0.05 was considered statistically significant.

    RESULTS: Coccidian parasitic infection accounted for about 23.4% of parasitic infections, and of these, Cystoisospora belli was observed to be the most common cause of diarrhoea (88.8%), followed by Cryptosporidium spp. (9.9%) and Cyclospora spp. (1.3%). Trend analysis of coccidian aetiology during the study period revealed a significant rise in the positivity of C. belli and Cryptosporidium spp. (P = 0.001). Among the HIV patients with CD4+ T-cell counts <200 cells/μL, Cryptosporidium infection was most common (90%), followed by infection with C. belli(61.4%).

    CONCLUSIONS: Coccidian parasites continue to be the most common aetiological agent of diarrhoea among patients with HIV. The increasing trend of positivity of both cystoisosporiasis and cryptosporidiosis over the study period and the high positivity of cryptosporidiosis in patients with lower CD4+ T-cell counts are issues of serious concern. The findings call for the need for the early diagnosis of coccidian parasites and appropriate intervention among HIV-infected patients.
    Matched MeSH terms: HIV Infections/immunology*
  5. Naftalin CM, Wong NS, Chan DP, Wong KH, Reidpath DD, Lee SS
    Int J STD AIDS, 2015 Oct;26(11):803-9.
    PMID: 25281539 DOI: 10.1177/0956462414553826
    To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.
    Matched MeSH terms: HIV Infections/immunology
  6. Ng KP, Saw TL, Baki A, He J, Singh N, Lyles CM
    Int J STD AIDS, 1999 Jun;10(6):401-4.
    PMID: 10414883
    Hema-Strip HIV-1/2 is a one-step rapid test for the detection of anti-HIV-1/2 antibodies in whole blood. The test requires no expensive equipment and the results are available within 10-15 min. Using 72 known HIV-1 positive samples and 780 high-risk prisoners, the sensitivity and specificity of Hema-Strip HIV-1/2 was found to be comparable to microparticle enzyme immunoassay (MEIA). The data also indicated that Hema-Strip HIV-1/2 is an effective alternate testing system to conventional ELISA where the use of ELISA is not suitable and the result of the HIV testing is needed urgently.
    Matched MeSH terms: HIV Infections/immunology*
  7. Oyomopito RA, Li PC, Sungkanuparph S, Phanuphak P, Tee KK, Sirisanthana T, et al.
    J Acquir Immune Defic Syndr, 2013 Mar 01;62(3):293-300.
    PMID: 23138836 DOI: 10.1097/QAI.0b013e31827a2e8f
    BACKGROUND: HIV-1 group M viruses diverge 25%-35% in envelope, important for viral attachment during infection, and 10%-15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunological, or virological treatment responses differed by genotype in treatment-naive patients initiating first-line therapy.

    METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.

    RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.

    CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.

    Matched MeSH terms: HIV Infections/immunology
  8. Ahn JY, Boettiger D, Law M, Kumarasamy N, Yunihastuti E, Chaiwarith R, et al.
    J Acquir Immune Defic Syndr, 2015 Jul 01;69(3):e85-92.
    PMID: 25850606 DOI: 10.1097/QAI.0000000000000634
    BACKGROUND: 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.

    METHODS: In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells per microliter who had CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1 CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells per microliter within a 6-month period (confirmed CD4 <200). A comparison of time with single and confirmed CD4 <200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprising the same patients with annual CD4 testing by removing every second CD4 count.

    RESULTS: Among 1538 patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells per microliter were significantly more likely to experience confirmed CD4 <200 compared with patients with higher baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P < 0.001 versus baseline CD4 ≥500 cells/μL]. Cumulative probabilities of confirmed CD4 <200 was also higher in patients with baseline CD4 200-249 cells per microliter compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4 <200 between biannual and annual CD4 measurement (P = 0.336).

    CONCLUSIONS: Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells per microliter may be sufficient for clinical management.

    Matched MeSH terms: HIV Infections/immunology
  9. 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: HIV Infections/immunology
  10. Rothan HA, Bidokhti MRM, Byrareddy SN
    J Autoimmun, 2018 05;89:11-20.
    PMID: 29352633 DOI: 10.1016/j.jaut.2018.01.002
    Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans. Many of DENV and CHIKV endemic regions have been experiencing outbreaks of ZIKV infection. Intriguingly, the mosquitoes, Aedes Aegypti and Aedes Albopictus, can simultaneously transmit all the combinations of ZIKV, DENV, and CHIKV to the humans. The co-circulation of these viruses leads to a complicated immune response due to the pre-existence or co-existence of ZIKV infection with DENV and CHIKV infections. The non-vector transmission of ZIKV, especially, via sexual intercourse and placenta represents an additional burden that may hander the treatment strategies of other sexually transmitted diseases such as HIV. Collectively, ZIKV co-circulation and co-infection with other viruses have inevitable impact on the host immune response, diagnosis techniques, and vaccine development strategies for the control of these co-infections.
    Matched MeSH terms: HIV Infections/immunology
  11. 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: HIV Infections/immunology*
  12. Ellegård R, Crisci E, Andersson J, Shankar EM, Nyström S, Hinkula J, et al.
    J Immunol, 2015 Aug 15;195(4):1698-704.
    PMID: 26157174 DOI: 10.4049/jimmunol.1500618
    Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.
    Matched MeSH terms: HIV Infections/immunology*
  13. Saeidi A, Ellegård R, Yong YK, Tan HY, Velu V, Ussher JE, et al.
    J Leukoc Biol, 2016 08;100(2):305-14.
    PMID: 27256572 DOI: 10.1189/jlb.4RU0216-084R
    MAIT cells represent an evolutionarily conserved, MR1-restricted, innate-like cell subset that express high levels of CD161; have a canonical semi-invariant TCR iVα7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161(hi)PLZF(hi)IL-18Rα(+)iVα7.2(+)γδ-CD3(+)CD8(+) T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T-bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL-7 to restore effector functions in HIV disease.
    Matched MeSH terms: HIV Infections/immunology*
  14. Mohamad Isa II, Abu Bakar S, Ab Rahman AK
    J Med Virol, 2020 08;92(8):1173-1181.
    PMID: 31957025 DOI: 10.1002/jmv.25680
    The impact of sociodemographic and clinical factors on immune recovery and viral load suppression among HIV-1 positive patients treated with HAART particularly in Malaysia is largely unknown. This cross-sectional study enrolled 170 HIV-1-infected individuals of three major ethnicities who attended three HIV outpatient clinics in Malaysia. Questionnaire was used to obtain sociodemographic data while CD4 count and viral load data were gathered from hospital's record. Multiple factors were assessed for their predictive effects on CD4 count recovery (≥500 cells/mm3 ) and viral load suppression (≤50 copies/mL) using binary logistic regression. Most of the subjects were male (149/87.6%), in the age group 30 to 39 years old (78/45.9%) and got infected via homosexual contact (82/48.2%). Indians were associated with 11 times higher chance for CD4 recovery as compared to Malays at 8 to 12 months of HAART (adjusted OR: 10.948, 95% CI: 1.873, 64.001, P = .008). Viral load suppression was positively influenced by intravenous drug use (IVDU) status (adjusted OR: 35.224, 95% CI: 1.234, 1000.489, P = .037) at 4 to 6 months of HAART. Higher pretreatment CD4 count was a positive predictor for both initial immunological and virological responses while higher pretreatment viral load was a negative predictor for virological suppression only. In conclusion, ethnicity plays a significant role in determining early immune reconstitution in Malaysia, besides pretreatment CD4 count. Further studies are needed to identify possible biological factors underlying this association.
    Matched MeSH terms: HIV Infections/immunology*
  15. Amar HS, Ho JJ, Mohan AJ
    J Paediatr Child Health, 1999 Feb;35(1):63-6.
    PMID: 10234638
    OBJECTIVE: To determine the community prevalence of human immunodeficiency virus (HIV) in women at the time of delivery in a Malaysian setting.

    METHODOLOGY: Cord blood samples from a pilot screening programme for congenital hypothyroidism in 1995 at Ipoh city and surrounding district hospitals were screened anonymously for HIV 1 and 2. HIV status was determined using chemiluminescent technology. Positive samples were retested using the Genelavia Mixt assay.

    RESULTS: A total of 4927 samples were tested. The ethnic breakdown included 51.7% Malays, 18.9% Chinese, 14.3% Indian, 2.3% Others and 12.9% unknown. The geographical distribution of samples was 73.9% urban, 24.2% rural and 1.9% unknown. The seroprevalence of HIV positivity was 3.25 per 1000 deliveries (95% CI: 1.92-5.16). Seroprevalence was higher for samples from rural and Malay mothers.

    CONCLUSION: The high seroprevalence in this study suggests that the spread of HIV is far wider than that anticipated by mandatory national reporting. It also supports antenatal screening and the use of antiretroviral therapy as an important strategy to reduce perinatal transmission.

    Matched MeSH terms: HIV Infections/immunology
  16. Jiamsakul A, Sungkanuparph S, Law M, Kantor R, Praparattanapan J, Li PC, et al.
    J Int AIDS Soc, 2014;17:19053.
    PMID: 25141905 DOI: 10.7448/IAS.17.1.19053
    First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART.
    Matched MeSH terms: HIV Infections/immunology
  17. Kiertiburanakul S, Boettiger D, Lee MP, Omar SF, Tanuma J, Ng OT, et al.
    J Int AIDS Soc, 2014;17(1):18804.
    PMID: 24598459 DOI: 18804
    INTRODUCTION: Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

    METHODS: Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm(3) or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

    RESULTS: A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46-241) cells/mm(3). Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm(3) in 2008 to a peak of 302 cells/mm(3) after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27-0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18-1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24-2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77-5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19-3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31-3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18-7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.-4.36; p=0.035).

    CONCLUSIONS: Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.

    Matched MeSH terms: HIV Infections/immunology
  18. Kosalaraksa P, Boettiger DC, Bunupuradah T, Hansudewechakul R, Saramony S, Do VC, et al.
    J Pediatric Infect Dis Soc, 2017 Jun 01;6(2):173-177.
    PMID: 27295973 DOI: 10.1093/jpids/piw031
    Background.: Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load.

    Methods: Study end points were as follows: (1) a CD4 count <200 cells/mm3 followed by a CD4 count ≥200 cells/mm3 (transient CD4 <200); (2) CD4 count <200 cells/mm3 confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4 <200, and clinical failure among virally suppressed children aged 5-15 years who were enrolled in the TREAT Asia Pediatric HIV Observational Database.

    Results: Data from 967 children were included in the analysis. At the time of confirmed viral suppression, median age was 10.2 years, 50.4% of children were female, and 95.4% were perinatally infected with HIV. Median CD4 cell count was 837 cells/mm3, and 54.8% of children were classified as having WHO stage 3 or 4 disease. In total, 18 transient CD4 <200 events, 2 confirmed CD4 <200 events, and10 clinical failures occurred at rates of 0.73 (95% confidence interval [95% CI], 0.46-1.16), 0.08 (95% CI, 0.02-0.32), and 0.40 (95% CI, 0.22-0.75) events per 100 patient-years, respectively. CD4 <500 cells/mm3 at the time of viral suppression confirmation was associated with higher rates of both CD4 outcomes.

    Conclusions: Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 ≥500 cells/mm3.

    Matched MeSH terms: HIV Infections/immunology
  19. Ansari AW, Schmidt RE, Shankar EM, Kamarulzaman A
    J Transl Med, 2014;12:341.
    PMID: 25528160 DOI: 10.1186/s12967-014-0341-8
    Even in the era of successful combination antiretroviral therapy (cART), co-infection of Hepatitis C virus (HCV) remains one of the leading causes of non-AIDS-related mortality and morbidity among HIV-positive individuals as a consequence of accelerated liver fibrosis and end-stage liver disease (ESLD). The perturbed liver microenvironment and induction of host pro-inflammatory mediators in response to HIV and HCV infections, play a pivotal role in orchestrating the disease pathogenesis and clinical outcomes. How these viruses communicate each other via chemokine CCL2 and exploit the liver specific cellular environment to exacerbate liver fibrosis in HIV/HCV co-infection setting is a topic of intense discussion. Herein, we provide recent views and insights on potential mechanisms of CCL2 mediated immuno-pathogenesis, and HIV-HCV cross-talk in driving liver inflammation. We believe CCL2 may potentially serve an attractive target of anti-fibrotic intervention against HIV/HCV co-infection associated co-morbidities.
    Matched MeSH terms: HIV Infections/immunology*
  20. Chang L, Lim BCW, Flaherty GT, Torresi J
    J Travel Med, 2019 Sep 02;26(6).
    PMID: 31066446 DOI: 10.1093/jtm/taz034
    BACKGROUND: With the advent of highly active antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) it has become possible for people with HIV to travel to destinations that may place them at risk of a number of infectious diseases. Prevention of infections by vaccination is therefore of paramount importance for these travellers. However, vaccine responsiveness in HIV-positive individuals is not infrequently reduced compared to HIV-negative individuals. An understanding of the expected immune responses to vaccines in HIV-positive travellers is therefore important in planning the best approach to a pretravel consultation.

    METHODS: A PubMed search was performed on HIV or acquired immune deficiency syndrome together with a search for specific vaccines. Review of the literature was performed to develop recommendations on vaccinations for HIV-positive travellers to high-risk destinations.

    RESULTS: The immune responses to several vaccines are reduced in HIV-positive people. In the case of vaccines for hepatitis A, hepatitis B, influenza, pneumococcus, meningococcus and yellow fever there is a good body of data in the literature showing reduced immune responsiveness and also to help guide appropriate vaccination strategies. For other vaccines like Japanese encephalitis, rabies, typhoid fever, polio and cholera the data are not as robust; however, it is still possible to gain some understanding of the reduced responses seen with these vaccines.

    CONCLUSION: This review provides a summary of the immunological responses to commonly used vaccines for the HIV-positive travellers. This information will help guide travel medicine practitioners in making decisions about vaccination and boosting of travellers with HIV.

    Matched MeSH terms: HIV Infections/immunology*
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