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The Journal of Infectious Diseases Nov 2023HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes... (Meta-Analysis)
Meta-Analysis
Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-analysis (2010-2021).
BACKGROUND
HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes (clades) across regions and populations is crucial. In this study, a systematic review of the past decade was conducted to characterize HIV-1/HIV-2 subtypes.
METHODS
A comprehensive search was performed in PubMed, EMBASE, and CABI Global Health, yielding 454 studies from 91 countries.
RESULTS
Globally, circulating recombinant forms (CRFs)/unique recombinant forms (URFs) accounted for 29% of HIV-1 strains, followed by subtype C (23%) and subtype A (17%). Among studies reporting subtype breakdowns in key populations, 62% of HIV infections among men who have sex with men (MSM) and 38% among people who inject drugs (PWIDs) were CRF/URFs. Latin America and the Caribbean exhibited a 25% increase in other CRFs (excluding CRF01_AE or CRF02_AG) prevalence between 2010-2015 and 2016-2021.
CONCLUSIONS
This review underscores the global distribution of HIV subtypes, with an increasing prevalence of CRFs and a lower prevalence of subtype C. Data on HIV-2 were limited. Understanding subtype diversity is crucial for vaccine development, which need to elicit immune responses capable of targeting various subtypes. Further research is needed to enhance our knowledge and address the challenges posed by HIV subtype diversity.
Topics: Male; Humans; HIV Infections; Homosexuality, Male; HIV-1; HIV-2; Genetic Variation; Phylogeny; Sexual and Gender Minorities; Prevalence; Genotype
PubMed: 37592824
DOI: 10.1093/infdis/jiad327 -
PloS One 2013Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting. (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting.
METHODS
We searched two databases up to June 30 2013 to identify randomized and quasi-randomized trials in which lamivudine and emtricitabine were used as part of combination antiretroviral therapy for treatment-naïve or experienced HIV-positive adult patients. We only included trials where partner drugs in the regimen were identical or could be considered to be comparable. We allowed for comparisons between tenofovir and abacavir provided the study population did not begin treatment with a viral load >100,000 copies/ml.
RESULTS
12 trials contributed 15 different randomized comparisons providing data on 2251 patients receiving lamivudine and 2662 patients receiving emtricitabine. Treatment success was not significantly different in any of the 12 trials. In the three trials that directly compared lamivudine and emtricitabine, the relative risk for achieving treatment success was non-significant (RR 1.03 95%CI 0.96-1.10). For all trials combined, the pooled relative risk for treatment success was not significantly different (RR 1.00, 95%CI 0.97-1.02). No heterogeneity was observed (I (2) = 0). Similarly, there was no difference in the pooled relative risk for treatment failure (RR 1.08, 95%CI 0.94-1.22, I (2) = 3.4%).
CONCLUSIONS
The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.
Topics: Adult; Anti-HIV Agents; Databases, Bibliographic; Deoxycytidine; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Lamivudine; Male; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Therapeutic Equivalency; Treatment Outcome; Viral Load
PubMed: 24244586
DOI: 10.1371/journal.pone.0079981 -
Journal of Infection and Public Health Jul 2020HIV/AIDS prevention has been widely adopted worldwide, but little is known about HIV/AIDS knowledge and attitudes in the Arabian Peninsula. (Meta-Analysis)
Meta-Analysis
BACKGROUND
HIV/AIDS prevention has been widely adopted worldwide, but little is known about HIV/AIDS knowledge and attitudes in the Arabian Peninsula.
AIM
To summarize the level of knowledge and attitude about HIV/AIDS in seven Arabian Peninsula countries (Saudi Arabia, Oman, Kuwait, Qatar, Bahrain, Yemen, and the United Arab Emirates (UAE)).
METHODS
A systematic literature search was performed using combined keywords in four scientific databases of peer-reviewed publications from January 2010 to June 2019. Twenty-five articles were included in the systematic review, and twenty studies in the meta-analysis. The data was analyzed using a random-effect model due to the heterogeneity between the studies.
RESULTS
Seventeen studies reported on the level of knowledge and overall knowledge about HIV/AIDS in this region: 74.4% (95% confidence interval (CI): 66.8%-82.0%, p<0.001) and the attitude was 52.8% (95% CI: 36.9%-68.6%, p<0.001). A study from Oman reported higher knowledge levels (95.5%, 95% CI: 94.2%-96.8%) while less than a quarter of the Bahrain population had positive attitudes 22.5% (95% CI: 20.5%-24.5%). Medical doctors showed higher knowledge (94.1%, 95% CI: 92.9%-95.3%), but a positive attitude was only observed in 32.5% (95% CI: 28.8%-36.2%) of the dentists toward HIV/AIDS.
CONCLUSION
The overall knowledge about HIV/AIDS was found to be satisfactory (74.4%), but about half (52.8%) of those displayed negative attitudes toward HIV/AIDS. Regular training courses as well as reviewing and reinforcing HIV/AIDS prevention guidelines can be useful to update knowledge and improve attitudes in this region.
Topics: Acquired Immunodeficiency Syndrome; Attitude; Female; HIV; HIV Infections; Health Knowledge, Attitudes, Practice; Humans; Male; Middle East; Physicians; Prisoners; Students; Surveys and Questionnaires
PubMed: 32359925
DOI: 10.1016/j.jiph.2020.04.002 -
American Journal of Public Health Jun 2013Despite the HIV "test-and-treat" strategy's promise, questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous... (Review)
Review
Despite the HIV "test-and-treat" strategy's promise, questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous debate in the global HIV community. We performed a systematic review of the literature published between January 2009 and May 2012 using PubMed, SCOPUS, Global Health, Web of Science, BIOSIS, Cochrane CENTRAL, EBSCO Africa-Wide Information, and EBSCO CINAHL Plus databases to summarize clinical uncertainties, health service challenges, and ethical complexities that may affect the test-and-treat strategy's success. A thoughtful approach to research and implementation to address clinical and health service questions and meaningful community engagement regarding ethical complexities may bring us closer to safe, feasible, and effective test-and-treat implementation.
Topics: HIV; HIV Infections; Health Promotion; Humans; Program Evaluation; Uncertainty
PubMed: 23597344
DOI: 10.2105/AJPH.2013.301273 -
Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581 -
Clinical Infectious Diseases : An... May 2023Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.
METHODS
Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).
RESULTS
Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.
CONCLUSIONS
There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
Topics: Adult; Adolescent; Child; Humans; Antitubercular Agents; Pyrazinamide; Ethambutol; Tuberculosis; Rifampin; Isoniazid; HIV; HIV Infections
PubMed: 36609692
DOI: 10.1093/cid/ciac973 -
Artificial Intelligence in Medicine Dec 2022Machine learning algorithms play an essential role in bioinformatics and allow exploring the vast and noisy biological data in unrivaled ways. This paper is a systematic... (Review)
Review
Machine learning algorithms play an essential role in bioinformatics and allow exploring the vast and noisy biological data in unrivaled ways. This paper is a systematic review of the applications of machine learning in the study of HIV neutralizing antibodies. This significant and vast research domain can pave the way to novel treatments and to a vaccine. We selected the relevant papers by investigating the available literature from the Web of Science and PubMed databases in the last decade. The computational methods are applied in neutralization potency prediction, neutralization span prediction against multiple viral strains, antibody-virus binding sites detection, enhanced antibodies design, and the study of the antibody-induced immune response. These methods are viewed from multiple angles spanning data processing, model description, feature selection, evaluation, and sometimes paper comparisons. The algorithms are diverse and include supervised, unsupervised, and generative types. Both classical machine learning and modern deep learning were taken into account. The review ends with our ideas regarding future research directions and challenges.
Topics: Humans; HIV Antibodies; Machine Learning; HIV-1; Antibodies, Neutralizing; HIV Infections
PubMed: 36462896
DOI: 10.1016/j.artmed.2022.102429 -
Clinical Therapeutics Jun 2022Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor...
PURPOSE
Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics.
METHODS
A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared.
FINDINGS
Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4 cell count of approximately 65 cells/mm from baseline through week 24 (mean difference = 7.05 cells/mm; 95% CI, -60.88 to 74.98 cells/mm; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4 cell count (135.78 cells/mm; 95% CI, 91.93-179.63 cells/mm; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4 cell count increase (26.86 cells/mm; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies.
IMPLICATIONS
Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1.
Topics: Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Viral Load
PubMed: 35610081
DOI: 10.1016/j.clinthera.2022.04.007 -
PLoS Medicine Apr 2017In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) issued treatment goals for human immunodeficiency virus (HIV). The 90-90-90 target specifies that by 2020,... (Review)
Review
BACKGROUND
In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) issued treatment goals for human immunodeficiency virus (HIV). The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART), and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target.
METHODS AND FINDINGS
For the period 2010-2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO), UNAIDS reports, national surveillance and program reports, United States President's Emergency Plan for AIDS Relief (PEPFAR) Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV) who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010-2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54%) of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden) were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia) were within 12% and 10% of achieving the 90-90-90 target for "on ART" and for "viral suppression," respectively. The limitations to consider when interpreting the results include significant variation in methods used to determine national continua and the possibility that complete continua were not available through our comprehensive search of the public domain.
CONCLUSIONS
Relatively few complete national continua of care are available in the public domain, and there is considerable variation in the methods for determining progress towards the 90-90-90 target. Despite bearing the highest HIV burden, national care continua from sub-Saharan Africa were less likely to be in the public domain. A standardized monitoring and evaluation approach could improve the use of scarce resources to achieve 90-90-90 through improved transparency, accountability, and efficiency.
Topics: Anti-HIV Agents; Databases, Factual; Disease Eradication; HIV Infections; HIV-1; Humans; Patient Care Planning; Public Health Surveillance; Public Sector; United Nations; World Health Organization
PubMed: 28376085
DOI: 10.1371/journal.pmed.1002253 -
The Lancet. Microbe May 2022HIV-1 pol sequences from antiretroviral therapy (ART)-naive and ART-experienced people living with HIV-1 are fundamental to understanding the genetic correlates and... (Review)
Review
HIV-1 pol sequences from antiretroviral therapy (ART)-naive and ART-experienced people living with HIV-1 are fundamental to understanding the genetic correlates and epidemiology of HIV-1 drug resistance (HIVDR). To assess the public availability of HIV-1 pol sequences and ART histories of the individuals from whom sequenced viruses were obtained, we performed a systematic review of PubMed and GenBank for HIVDR studies published between 2010 and 2019 that reported HIV-1 pol sequences. 934 studies met inclusion criteria, including 461 studies of ART-naive adults, 407 of ART-experienced adults, and 66 of ART-naive and ART-experienced children. Sequences were available for 317 (68·8%) studies of ART-naive individuals, 190 (46·7%) of ART-experienced individuals, and 45 (68·2%) of children. Among ART-experienced individuals, sequences plus linked ART histories were available for 82 (20·1%) studies. Sequences were available for 21 (29·2%) of 72 clinical trials. Among journals publishing more than ten studies, the proportion with available sequences ranged from 8·3% to 86·9%. Strengthened implementation of data sharing policies is required to increase the number of studies with available HIVDR data to support the enterprise of global ART in the face of emerging HIVDR.
Topics: Adult; Anti-HIV Agents; Child; Drug Resistance, Viral; HIV Infections; HIV Seropositivity; HIV-1; Humans; Mutation; Viral Load
PubMed: 35544100
DOI: 10.1016/S2666-5247(21)00250-0