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  1. Desgrees-du-Lou A, Pannetier J, Ravalihasy A, Le Guen M, Gosselin A, Panjo H, et al.
    AIDS, 2016 Feb 20;30(4):645-56.
    PMID: 26558722 DOI: 10.1097/QAD.0000000000000957
    In Europe, sub-Saharan African migrants are a key population for HIV infection. We analyse how social hardships during settlement in France shape sexual partnerships and HIV risk.
  2. Cain LE, Phillips A, Lodi S, Sabin C, Bansi L, Justice A, et al.
    AIDS, 2012 Aug 24;26(13):1691-705.
    PMID: 22546987
    OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes.

    DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.

    METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.

    RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.

    CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.

  3. HIV-CAUSAL Collaboration, Ray M, Logan R, Sterne JA, Hernández-Díaz S, Robins JM, et al.
    AIDS, 2010 Jan 02;24(1):123-37.
    PMID: 19770621 DOI: 10.1097/QAD.0b013e3283324283
    OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.

    DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.

    RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).

    CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

  4. Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, et al.
    AIDS, 2013 Sep 24;27(15):2403-11.
    PMID: 23921615 DOI: 10.1097/01.aids.0000432534.47217.b4
    To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.
  5. Lim A, Tan D, Price P, Kamarulzaman A, Tan HY, James I, et al.
    AIDS, 2007 Jul 31;21(12):1525-34.
    PMID: 17630546
    To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR).
  6. Aceijas C, Stimson GV, Hickman M, Rhodes T, United Nations Reference Group on HIV/AIDS Prevention and Care among IDU in Developing and Transitional Countries
    AIDS, 2004 Nov 19;18(17):2295-303.
    PMID: 15577542
    OBJECTIVE: To provide global estimates of the prevalence of injecting drug use (IDU) and HIV prevalence among IDU, in particular to provide estimates for developing and transitional countries.

    METHODS: Collation and review of existing estimates of IDU prevalence and HIV prevalence from published and unpublished documents for the period 1998-2003. The strength of evidence for the information was assessed based on the source and type of study.

    RESULTS: Estimates of IDU prevalence were available for 130 countries. The number of IDU worldwide was estimated as approximately 13.2 million. Over ten million (78%) live in developing and transitional countries (Eastern Europe and Central Asia, 3.1 million; South and South-east Asia, 3.3 million; East-Asia and Pacific, 2.3 million). Estimates of HIV prevalence were available for 78 countries. HIV prevalence among IDU of over 20% was reported for at least one site in 25 countries and territories: Belarus, Estonia, Kazakhstan, Russia, Ukraine, Italy, Netherlands, Portugal, Serbia and Montenegro, Spain, Libya, India, Indonesia, Malaysia, Myanmar, Nepal, Thailand, Viet Nam, China, Argentina, Brazil, Uruguay, Puerto Rico, USA and Canada.

    CONCLUSIONS: These findings update previous assessments of the number of countries with IDU and HIV-infected IDU, and the previous quantitative global estimates of the prevalence of IDU. However, gaps remain in the information and the strength of the evidence often was weak.

  7. Tee KK, Pon CK, Kamarulzaman A, Ng KP
    AIDS, 2005 Jan 28;19(2):119-26.
    PMID: 15668536
    OBJECTIVES: To investigate the molecular epidemiology of HIV-1 and to screen for the emergence of intersubtype recombinants in Kuala Lumpur, Malaysia.

    DESIGN: A molecular epidemiology study was conducted among HIV-1 seropositive patients attending the University Malaya Medical Center (UMMC) from July 2003 to June 2004.

    METHODS: Protease (PR) and reverse transcriptase (RT) gene sequences were derived from drug resistance genotyping assay of 100 newly diagnosed or antiretroviral-naive patients. These were phylogenetically analysed to determine the subtypes and recombination breakpoint analyses were performed on intersubtype recombinants to estimate the recombination breakpoint(s).

    RESULTS: CRF01_AE predominated in Kuala Lumpur with 65% in both PR and RT genes. B subtype was detected at 14% and 12% in PR and RT genes, respectively. C subtype was present at 1% in both genes. Overall, the concordance of PR and RT genes in discriminating subtypes/circulating recombinant forms (CRF) was high at 96%. In this study, novel CRF01_AE/B intersubtype recombinants were detected at high prevalence (22%), including those isolates with subtype discordance. Thai variants of CRF01_AE and B subtype were involved in the genesis of these unique recombinant forms (URF). Interestingly, 19 CRF01_AE/B intersubtype recombinant isolates shared similar recombination breakpoints in both PR and RT genes. Several distinct URF were also identified.

    CONCLUSION: PR and RT genes can be utilized for subtype/CRF assessment with high degree of agreement, allowing concurrent surveillance of circulating HIV-1 subtypes with antiretroviral drug resistance genotyping tests. The emergence of highly identical CRF01_AE/B intersubtype recombinants suggests the possibility of the appearance of a new circulating recombinant form in Kuala Lumpur.

  8. Ismail R
    AIDS, 1998;12 Suppl B:S33-41.
    PMID: 9679627
  9. Pakianathan MR, Kamarulzaman A, Ismail R, McMillan A, Scott GR
    AIDS, 1999 Sep 10;13(13):1787-8.
    PMID: 10509585
  10. Crofts N, Costigan G, Narayanan P, Gray J, Dorabjee J, Langkham B, et al.
    AIDS, 1998;12 Suppl B:S109-15.
    PMID: 9679636
  11. AIDS, 1999 Jul 30;13(11):UNAIDS 1-UNAIDS 13.
    PMID: 10449273
    A meeting was organized by the Joint United Nations Programme on HIV/AIDS (UNAIDS), the World Health Organisation (WHO) and the Japanese National Institute of Infectious Diseases (NIID) with the following objectives: (i) to discuss public health and economic rationale to accelerate the development and evaluation of HIV vaccines suitable for use in Asia; (ii) to review ongoing preclinical HIV vaccine research in Asia; (iii) to review the Asian experience in conducting clinical trials of HIV candidate vaccines; (iv) to explore possibilities for international collaboration between countries in the region and with other countries and institutions; and (v) to discuss issues related to availability of future effective HIV vaccines. The meeting was attended by participants from Australia, China, France, Germany, India, Japan, Malaysia, Myanmar, South Korea, Thailand, United Kingdom, and the United States of America. The HIV epidemic in Asia is rapidly spreading and has already resulted in a total of 7 million HIV infections in the region. The epidemic already has a significant public health and economic impact, which may be worse in the future, unless effective intervention programmes are successfully implemented. A safe, effective, and affordable vaccine should be considered as the best hope for a long-term solution to the HIV epidemic in Asia. Asian scientists and institutions have established a number of international collaborations to isolate and characterize prevalent HIV-1 strains (mostly belonging to subtypes C and E) and are developing candidate vaccines based on these subtypes. In the region, phase I/II clinical trials of preventative HIV candidate vaccines have been conducted in Australia, China and Thailand. Since 1993, a comprehensive National AIDS Vaccine Plan has allowed Thailand to conduct phase I/II trials of six different preventative or therapeutic candidate vaccines, and the first phase III preventative efficacy trial has been approved. The meeting identified both the needs and the opportunities to intensify international collaboration to accelerate the development of HIV vaccines in Asia.
  12. Singh J, Che'Rus S, Chong S, Chong YK, Crofts N
    AIDS, 1994;8 Suppl 2:S99-103.
    PMID: 7857575
  13. Weniger BG, Takebe Y, Ou CY, Yamazaki S
    AIDS, 1994;8 Suppl 2:S13-28.
    PMID: 7857556
  14. Kaldor JM, Sittitrai W, John TJ, Kitamura T
    AIDS, 1994;8 Suppl 2:S1-2.
    PMID: 7857551
  15. Tan HY, Yong YK, Andrade BB, Shankar EM, Ponnampalavanar S, Omar SF, et al.
    AIDS, 2015 Feb 20;29(4):421-31.
    PMID: 25565499 DOI: 10.1097/QAD.0000000000000557
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS.
  16. 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 

  17. 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 
  18. Bartlett AW, Truong KH, Songtaweesin WN, Chokephaibulkit K, Hansudewechakul R, Ly PS, et al.
    AIDS, 2018 07 31;32(12):1689-1697.
    PMID: 29794827 DOI: 10.1097/QAD.0000000000001883
    OBJECTIVES: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition.

    DESIGN: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia.

    METHODS: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation.

    RESULTS: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART.

    CONCLUSION: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.

  19. Rajasuriar R, Palmer C, Abdel-Mohsen M, Kamaruzzaman SB
    AIDS, 2019 02 01;33(2):345-347.
    PMID: 30562173 DOI: 10.1097/QAD.0000000000002064
  20. Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.
    AIDS, 2018 05 15;32(8):1025-1034.
    PMID: 29547442 DOI: 10.1097/QAD.0000000000001798
    OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.

    DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.

    METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.

    RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).

    CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.

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