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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 -
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 -
Annals of Behavioral Medicine : a... Jan 2023People with human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease (CVD) not fully accounted for by traditional or HIV-specific risk...
BACKGROUND
People with human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease (CVD) not fully accounted for by traditional or HIV-specific risk factors. Successful management of HIV does not eliminate this excess risk. Thus, there is a need to identify novel risk factors for CVD among people with HIV (PWH).
PURPOSE
Our objective was to systematically review the literature on one such candidate CVD risk factor in PWH-depression.
METHODS
A systematic literature search of PubMed, PsycINFO, EMBASE, Web of Science, and CINAHL was performed to identify published English-language studies examining associations of depression with clinical CVD, subclinical CVD, and biological mechanisms (immune activation, systemic inflammation, altered coagulation) among PWH between the earliest date and June 22, 2021.
RESULTS
Thirty-five articles were included. For clinical CVD (k = 8), findings suggests that depression is consistently associated with an increased risk of incident CVD. For subclinical CVD (k = 5), one longitudinal analysis reported a positive association, and four cross-sectional analyses reported null associations. For immune activation (k = 13), systemic inflammation (k = 17), and altered coagulation (k = 5), findings were mixed, and there was considerable heterogeneity in sample characteristics and methodological quality across studies.
CONCLUSIONS
Depression may be an independent risk factor for CVD among PWH. Additional research is needed to confirm depression's association with clinical CVD and to determine whether depression is consistently and meaningfully associated with subclinical CVD and biological mechanisms of CVD in HIV. We propose a research agenda for this emerging area.
Topics: Humans; HIV; Cardiovascular Diseases; HIV Infections; Cross-Sectional Studies; Depression; Risk Factors; Inflammation
PubMed: 35481701
DOI: 10.1093/abm/kaab119 -
Frontiers in Immunology 2022We aimed to analyze HIV-1 seroreversion caused by combination antiretroviral therapy (cART) and to explore antibody levels of anti-HIV-1 as an alternative biomarker of... (Meta-Analysis)
Meta-Analysis
We aimed to analyze HIV-1 seroreversion caused by combination antiretroviral therapy (cART) and to explore antibody levels of anti-HIV-1 as an alternative biomarker of HIV-1 reservoir. We searched PubMed, Embase, the Cochrane Library, and Web of Science up to August 2021 for publications about the performance of HIV-1 serological assays or the association between antibody responses against HIV-1 and HIV-1 reservoirs. Potential sources of heterogeneity were explored by meta-regression analysis, including the year of publication, country, pretreatment viral load, sample size, the timing of treatment, time on cART, and principle or type of serological assay. Twenty-eight eligible studies with a total population of 1,883 were included in the meta-analysis. The pooled frequency of HIV-1 seronegativity is 38.0% (95% CI: 28.0%-49.0%) among children with vertical HIV-1 infection and cART initiation at the age of less than 6 months, while the percentage of HIV-1 seronegativity declined to 1.0% (95% CI: 0%-3.0%) when cART was initiated at the age of >6 months. For adult patients, 16.0% (95% CI: 9.0%-24.0%) of them were serologically negative when cART was initiated at acute/early infection of HIV-1, but the seronegative reaction was rarely detected when cART was started at chronic HIV-1 infection. Substantial heterogeneity was observed among the studies to estimate the frequency of HIV-1 seronegativity in the early-cART population ( ≥ 70%, < 0.05 and all), while mild heterogeneity existed for the deferred-cART subjects. Moreover, anti-HIV-1 antibody response positively correlates with HIV-1 reservoir size with a pooled rho of 0.43 (95% CI: 0.28-0.55), suggesting that anti-HIV antibody level may be a feasible biomarker of HIV-1 reservoir size.
Topics: Adult; Antiretroviral Therapy, Highly Active; Child; HIV Infections; HIV Seropositivity; HIV-1; Humans; Infant; Viral Load
PubMed: 35432309
DOI: 10.3389/fimmu.2022.844023 -
Frontiers in Public Health 2022To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995.
AIM
To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995.
DESIGN
This Systematic Review used PECO criteria follow by PRISMA reporting guidelines and registered as CRD42021279062 (Prospero database). The Newcastle-Ottawa Scale assessed the methodological quality of included studies.
DATA COLLECTION AND ANALYSIS
A systematical search in PubMed/MEDLINE, Embase, Web of Sciences databases for cross-sectional, case-control, or cohort studies design to identify clinical and laboratorial outcomes related to HIV-1 and HTLV-1/2 coinfection. Search strategy: [("HIV-1" AND "HTLV-1" OR "HTLV-2") AND ("Coinfection") AND (1990/01/01:2021/12/31[Date- Publication])].
RESULTS
A total of 15 articles were included on this systematic review describing data of 2,566 mono and coinfected patients, 58% male, with mean age was 35.7 ± 5.7 years. HIV-1 and HTLV-1 coinfected patients were more likely to had shorter survival and faster progression to death or mortality than monoinfected ones. Coinfected had higher CD4 cell counts and less likelihood of ART use. In addition, higher frequency of diseases like ichthyosis (22.2 vs. 6.8%), scabies (18.6 vs. 0%), candidiasis (42 vs. 12%), Strongyloidiasis (15.4 vs. 2%) and neurological manifestations like encephalopathy, peripheral neuropathy and HAM/TSP were more frequently reported in coinfected patients.
CONCLUSIONS
HIV-1 and HTLV-1 coinfection and HIV-1 and HTLV-1 /2 triple coinfection were related to shorter survival, higher mortality rate, and faster progression to death, while coinfection by HIV-1/HTLV-2 seems to have neutral association with longer survival, slower AIDS progression, and lower mortality rate. The available evidence indicates an urgent need for prevention and control measures, including screening, diagnosis, and treatment of HIV-1 and HTLV-1/2 coinfected patients. Test-and-treat strategy for patients living with HIV in areas endemic for HTLV infection is mandatory, to avoid the risks of delayed therapy and death for coinfected patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021279062.
Topics: Adult; Coinfection; Cross-Sectional Studies; Female; HIV Infections; HIV-1; HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Male
PubMed: 35359787
DOI: 10.3389/fpubh.2022.820727 -
Japanese Journal of Infectious Diseases Sep 2022To maintain the performance quality, human immunodeficiency virus (HIV) in vitro diagnostic (IVD) kits are required to be evaluated by unbiased health regulatory... (Meta-Analysis)
Meta-Analysis
Diagnostic Accuracy of Human Immunodeficiency Virus In Vitro Assays Evaluated by the World Health Organization Prequalification Evaluation Laboratories: Systematic Review and Meta-Analysis.
To maintain the performance quality, human immunodeficiency virus (HIV) in vitro diagnostic (IVD) kits are required to be evaluated by unbiased health regulatory organizations following predefined guidelines. The World Health Organization (WHO) prequalification is one such program for the evaluation of IVD assays. In the present systematic review and meta-analysis, we analyzed and compared the 17 WHO prequalified public reports of HIV IVDs to yield summarized information for performance parameters. Pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were used as overall performance evaluation parameters. High (≥98%) and comparable levels of sensitivity and specificity were observed for most of the assays. In addition, the overall diagnostic efficiency was observed to attain high precision, as evident by the value of the area under the curve (AUC) for the hierarchical summary receiver operating characteristic curve (AUC ≥ 0.98).
Topics: HIV; HIV Infections; Humans; Laboratories; ROC Curve; Sensitivity and Specificity; World Health Organization
PubMed: 35354705
DOI: 10.7883/yoken.JJID.2021.720 -
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 -
Nature Communications Mar 2022Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but... (Meta-Analysis)
Meta-Analysis
Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but lack of centralized databases is hampering an overall outcomes assessment. Here we aim to provide a comprehensive assessment of the short and long term safety of HSPC-GT from trials using different vector platforms. We review systematically the literature on HSPC-GT to describe survival, genotoxicity and engraftment of gene corrected cells. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death is 0.9 per 100 person-years of observation (PYO) (95% CI = 0.37-2.17). There are 21 genotoxic events out of 1504.02 PYO, which occurred in γRV trials (0.99 events per 100 PYO, 95% CI = 0.18-5.43) for primary immunodeficiencies. Pooled rate of engraftment is 86.7% (95% CI = 67.1-95.5%) for γRV and 98.7% (95% CI = 94.5-99.7%) for LV HSPC-GT (p = 0.005). Our analyses show stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPCs.
Topics: Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lentivirus
PubMed: 35288539
DOI: 10.1038/s41467-022-28762-2 -
PloS One 2022Early infant diagnosis (EID) of HIV infection increases antiretroviral therapy initiation, which reduces pediatric HIV-related morbidity and mortality. This review aims... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Early infant diagnosis (EID) of HIV infection increases antiretroviral therapy initiation, which reduces pediatric HIV-related morbidity and mortality. This review aims to critically appraise the effects of interventions to increase uptake of early infant diagnosis.
DESIGN
This is a systematic review and meta-analysis of interventions to increase the EID of HIV infection. We searched PubMed, EMBASE, CINAHL, and PsycINFO to identify eligible studies from inception of these databases to June 18, 2020. EID Uptake at 4-8 weeks of age was primary outcome assessed by the review. We conducted meta-analysis, using data from reports of included studies. The measure of the effect of dichotomous data was odds ratios (OR), with a 95% confidence interval. The grading of recommendations assessment, development, and evaluation (GRADE) approach was used to assess quality of evidence.
SETTINGS
The review was not limited by time of publication or setting in which the studies conducted.
PARTICIPANTS
HIV-exposed infants were participants.
RESULTS
Database search and review of reference lists yielded 923 unique titles, out of which 16 studies involving 13,822 HIV exposed infants (HEI) were eligible for inclusion in the review. Included studies were published between 2014 and 2019 from Kenya, Nigeria, Uganda, South Africa, Zambia, and India. Of the 16 included studies, nine (experimental) and seven (observational) studies included had low to moderate risk of bias. The studies evaluated eHealth services (n = 6), service improvement (n = 4), service integration (n = 2), behavioral interventions (n = 3), and male partner involvement (n = 1). Overall, there was no evidence that any of the evaluated interventions, including eHealth, health systems improvements, integration of EID, conditional cash transfer, mother-to-mother support, or partner (male) involvement, was effective in increasing uptake of EID at 4-8 weeks of age. There was also no evidence that any intervention was effective in increasing HIV-infected infants' identification at 4-8 weeks of age.
CONCLUSIONS
There is limited evidence to support the hypothesis that interventions implemented to increase uptake of EID were effective at 4-8 weeks of life. Further research is required to identify effective interventions that increase early infant diagnosis of HIV at 4-8 weeks of age.
PROSPERO NUMBER
(CRD42020191738).
Topics: Early Diagnosis; Female; HIV; HIV Infections; Humans; India; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Kenya; Male; Mothers; Nigeria; South Africa; Uganda; Zambia
PubMed: 35213579
DOI: 10.1371/journal.pone.0258863 -
Journal of Clinical Epidemiology Aug 2022To estimate the prevalence of NRTI and NNRTI drug resistance mutations in patients failing NNRTI-based ART in Southern Africa. (Review)
Review
OBJECTIVE
To estimate the prevalence of NRTI and NNRTI drug resistance mutations in patients failing NNRTI-based ART in Southern Africa.
STUDY DESIGN
We conducted a systematic review to identify studies reporting drug resistance mutations among adult people living with HIV (PLWH) who experienced virological failure on first-line NNRTI-based ART in Southern Africa. We used a Bayesian hierarchical meta-regression model to synthesize the evidence on the frequency of eight NRTI- and seven NNRTI-DRMs across different ART regimens, accounting for ART duration and study characteristics.
RESULTS
We included 19 study populations, including 2,690 PLWH. Patients failing first-line ART including emtricitabine or lamivudine showed high levels of the M184V/I mutation after 2 years: 75.7% (95% Credibility Interval [CrI] 61.9%-88.9%) if combined with tenofovir, and 72.1% (95% CrI 56.8%-85.9%) with zidovudine. With tenofovir disoproxil fumarate, the prevalence of the K65R mutation was 52.0% (95% CrI 32.5%-76.8%) at 2 years. On efavirenz, K103 was the most prevalent NNRTI resistance mutation (57.2%, 95% CrI 40.9%-80.1%), followed by V106 (46.8%, 95% CrI 31.3%-70.4%).
CONCLUSIONS
NRTI/NNRTI drug resistance mutations are common in patients failing first-line ART in Southern Africa. These patients might switch to dolutegravir-based regimen with compromised NRTIs, which could impair the long-term efficacy of ART.
Topics: Adult; Humans; Lamivudine; Zidovudine; Drug Resistance, Viral; HIV-1; Viral Load; Bayes Theorem; HIV Infections; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Mutation
PubMed: 35192922
DOI: 10.1016/j.jclinepi.2022.02.005