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The Cochrane Database of Systematic... May 2017Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010.
OBJECTIVES
To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women).
SEARCH METHODS
We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials.
SELECTION CRITERIA
We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrientsWe conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI -22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD -0.1 logviral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium.In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrientsNone of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient.
AUTHORS' CONCLUSIONS
The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects.These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals.
Topics: Adult; CD4 Lymphocyte Count; Cause of Death; Child; Dietary Supplements; Female; HIV Infections; HIV-1; HIV-2; Hospitalization; Humans; Micronutrients; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Selenium; Viral Load; Vitamin A; Vitamin D; Vitamins; Zinc; beta Carotene
PubMed: 28518221
DOI: 10.1002/14651858.CD003650.pub4 -
Clinical Microbiology and Infection :... Jun 2021People living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
People living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR).
METHODS
We searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance.
RESULTS
In total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcusaureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36-3.30) higher odds for colonization and 1.90 (95%CI 1.45-2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75-2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae.
CONCLUSION
This review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; HIV Infections; HIV-1; Humans
PubMed: 33813126
DOI: 10.1016/j.cmi.2021.03.026 -
The Cochrane Database of Systematic... Jul 2014PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5 antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV). This may be an effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5 antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV). This may be an effective new treatment with the potential to address the limitations of currently available therapies for HIV-infected patients.
OBJECTIVES
We aimed to assess the efficacy, safety, clinical disease progression and immunologic (CD4 count/percentage) and virologic (plasma HIV RNA viral load) markers of PRO 140 for HIV-infected patients in randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs).
SEARCH METHODS
We searched databases including The Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 4), MEDLINE (PubMed, January 1966 to April 2014), EMBASE (January 1978 to April 2014) and ISI Web of Knowledge (January 1966 to April 2014), online trials registries and other sources. We also screened the reference lists of related literature and eligible studies, and presentations from major HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) conferences.
SELECTION CRITERIA
We included RCTs and quasi-RCTs comparing PRO 140 with placebo or other antiretroviral drugs, or different doses of PRO 140 for individuals infected with HIV.
DATA COLLECTION AND ANALYSIS
Two reviewers (L Li and JH Tian) independently screened all retrieved citations and selected eligible studies. Two authors (P Zhang and WQ Jia) independently extracted data. Any disagreements when selecting studies and extracting data were adjudicated by the review mentor (KH Yang). We used Review Manager (RevMan) software for statistical analysis based on an intention-to-treat analysis. We examined heterogeneity using the Chi(2) statistic. We regarded I(2) estimates greater than 50% as moderate or high levels of heterogeneity. According to the level of heterogeneity, we used either a fixed or random-effects model.If significant heterogeneity existed and the reasons could not be found, we reported the results qualitatively.
MAIN RESULTS
We included three trials comparing PRO 140 with placebo in adult patients with HIV infection. Our review indicates that PRO 140 may offer significant dose-dependent HIV-1 RNA suppression with tolerable side effects. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly showed statistically significant differences in the changes of HIV-1 RNA levels. HIV-1 RNA levels were reduced by intravenous (IV) infusion of PRO 140 2 mg/kg or 5 mg/kg on day 10, 5 mg/kg or 10 mg/kg on day 12, 162 mg weekly, 324 mg biweekly, or 324 mg weekly on day 22. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly demonstrated greater antiviral response. PRO 140 324 mg weekly, 5 mg/kg, and 10 mg/kg showed more patients with ≦ 400 copies/mL HIV-1 RNA. Only PRO 140 5 mg/kg showed greater change in CD4(+) cell count on day eight. Headache, lymphadenopathy, diarrhoea, fatigue, hypertension, nasal congestion and pruritus were reported to be the most frequent adverse events.
AUTHORS' CONCLUSIONS
Limited evidence from three small trials suggests that PRO 140 might demonstrate potent, short-term, dose-dependent, highly significant antiviral activity. However, as the evidence is insufficient, recommendations cannot yet be made. Larger, longer-term, double-blind RCTs are required to provide conclusive evidence.
Topics: Adult; Anti-HIV Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CCR5 Receptor Antagonists; Drug Administration Schedule; HIV Antibodies; HIV Infections; HIV-1; Humans; RNA, Viral; Randomized Controlled Trials as Topic
PubMed: 25063928
DOI: 10.1002/14651858.CD008439.pub3 -
PloS One 2014HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including... (Review)
Review
BACKGROUND
HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including storage and transport limitations for whole blood and plasma. Data from various studies indicate that HIV RNA is stable beyond current recommendations. We conducted a systematic review to assess stability data of HIV RNA in whole blood and plasma across times and temperatures.
METHODS AND FINDINGS
Using a pre-defined protocol, five databases were searched for studies where blood samples from HIV patients were stored at time and temperature points that exceeded manufacturer recommendations. RNA stability, the primary outcome, was measured by the difference in means compared to samples stored within established thresholds. RNA stability was defined as ≤0.5 log degradation. The search identified 10,716 titles, of which nine full-text articles were included for review. HIV RNA maintained stability in EDTA whole blood and plasma at all measured time points up to 168 hours when stored at 4°C, while stability was detected at 72 hours (95% confidence) in whole blood at 25°C, with data points before and beyond 72 hours suggesting stability but not reaching statistical significance. For EDTA plasma stored at 30°C, stability was maintained up to 48 hours (95% confidence), with OLS linear regression estimates up to 127 hours, suggesting stability. Overall, quality of studies was moderate. Limitations included small sample sizes, few studies meeting inclusion criteria, and no studies examining RNA stability in low viremia (<3,000 copies/mL) environments.
CONCLUSIONS
Whole blood and plasma samples in EDTA may remain stable under conditions exceeding current manufacturer recommendations for HIV VL testing. However, given the limited number of studies addressing this question, especially at low levels of viremia, additional evaluations on HIV RNA stability in EDTA tubes and PPT in field conditions are needed.
Topics: Edetic Acid; HIV Infections; HIV-1; Humans; RNA Stability; RNA, Viral; Specimen Handling; Temperature; Viral Load
PubMed: 25437009
DOI: 10.1371/journal.pone.0113813 -
PloS One 2023Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing,... (Meta-Analysis)
Meta-Analysis
Barriers and facilitators to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review and meta-analysis.
BACKGROUND
Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing, treatment, and retention to care are low among adolescents. We conducted a mixed-method systematic review to assess anti-retroviral therapy (ART) adherence; barriers and facilitators to ART adherence and ART outcomes among adolescents living with HIV and on ART in sub-Saharan Africa.
METHODS
We conducted searches in four scientific databases for studies conducted between 2010 and March 2022 to identify relevant primary studies. Studies were screened against inclusion criteria and assessed for quality, and data was extracted. Meta-analysis of rates and odd ratios was used to plot the quantitative studies and meta-synthesis summarized the evidence from qualitative studies.
RESULTS
A total of 10 431 studies were identified and screened against the inclusion/ exclusion criteria. Sixty-six studies met the inclusion criteria (41 quantitative, 16 qualitative, and 9 mixed-methods study designs). Fifty-three thousand two hundred and seventeen (53 217) adolescents (52 319 in quantitative studies and 899 in qualitative studies) were included in the review. Thirteen support focused interventions for improved ART adherence were identified from quantitative studies. The plotted results from the meta-analysis found an ART adherence rate of 65% (95%CI 56-74), viral load suppression was 55% (95%CI 46-64), un-suppressed viral load rate of 41% (95%CI 32-50), and loss to follow up of 17% (95%CI 10-24) among adolescents. Meta-synthesis found six themes of barriers to ART (social, patient-based, economic, health system-based, therapy-based, and cultural barriers) in both the qualitative and quantitative studies, and three themes of facilitators to ART were also identified (social support, counselling, and ART education and secrecy or confidentiality) from qualitative studies.
CONCLUSION
ART adherence remains low among adolescents in SSA despite multiple interventions implemented to improve ART adherence. The low adherence rate may hinder the attainment of the UNAIDS 2030 targets. Additionally, various barriers to ART adherence due to lack of support have been reported among this age group. However, interventions aimed at improving social support, educating, and counselling adolescents may improve and sustain ART adherence.
TRIAL REGISTRATION
Systematic review registration: PROSPERO CRD42021284891.
Topics: Humans; Adolescent; HIV; Medication Adherence; HIV Infections; Anti-HIV Agents; Africa South of the Sahara; Anti-Retroviral Agents
PubMed: 37200399
DOI: 10.1371/journal.pone.0276411 -
PloS One 2023Nine in ten of the world's 1.74 million adolescents living with human immunodeficiency virus (ALHIV) live in Sub-Saharan Africa. Suboptimal adherence to antiretroviral... (Meta-Analysis)
Meta-Analysis
The association between HIV diagnosis disclosure and adherence to anti-retroviral therapy among adolescents living with HIV in Sub-Saharan Africa: A systematic review and meta-analysis.
INTRODUCTION
Nine in ten of the world's 1.74 million adolescents living with human immunodeficiency virus (ALHIV) live in Sub-Saharan Africa. Suboptimal adherence to antiretroviral therapy (ART) and poor viral suppression are important problems among adolescents. To guide intervention efforts in this regard, this review presented pooled estimates on the prevalence of adherence and how it is affected by disclosure of HIV status among ALHIV in Sub-Saharan Africa.
METHODS
A comprehensive search in major databases (Excerpta Medica database (EMBASE), PubMed, Ovid/MEDLINE, HINARI, and Google Scholar) with additional hand searches for grey literature was conducted to locate observational epidemiologic studies published in English up to November 12, 2022 with the following inclusion criteria: primary studies that reported disclosure of HIV status as an exposure variable, had positive adherence to ART as an outcome, and conducted among adolescents and children. The COVIDENCE software was used for a title/abstract screening, full-text screening, the JBI quality assessment checklist, and data extraction. Random effects model was used to pool estimates. Furthermore, sensitivity analysis and subgroup analysis were also conducted by age groups and type of adherence measures used.
RESULTS
This meta-analysis combines the effect estimates from 12 primary studies with 4422 participants. The prevalence of good adherence to ART was 73% (95% CI (confidence interval): 56 to 87; I2 = 98.63%, P = <0.001), and it was higher among adolescents who were aware of their HIV status, 77% (95% CI: 56 to 92; I2 = 98.34%, P = <0.001). Overall, knowledge of HIV status was associated with increased odds of adherence (odds ratio (OR) = 1.88, 95% CI: 1.21 to 2.94; I2 = 79.8%, P = <0.001). This was further supported in a subgroup analysis by age (seven studies, pooled OR = 1.89, 95% CI: 1.06 to 3.37; I2 = 81.3%, P = <0.0001) and whether primary studies controlled for confounding factors (six studies provided adjusted estimates, pooled OR = 2.61, 95% CI: 1.22 to 5.57; I2 = 88.1%, P = <0.001) confirmed this further.
CONCLUSIONS
Our meta-analysis and systematic review revealed that knowledge of one's HIV status was associated with adherence to ART, particularly among adolescents. The findings underscored the importance of encouraging disclosure in order to enhance adherence among adolescents.
Topics: Child; Humans; Adolescent; HIV; Disclosure; Medication Adherence; HIV Infections; Africa South of the Sahara
PubMed: 37167342
DOI: 10.1371/journal.pone.0285571 -
Microbiology and Molecular Biology... Sep 2016The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host... (Review)
Review
The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.
Topics: Drug Resistance, Viral; Gene Expression Profiling; Genome, Viral; HIV Envelope Protein gp120; HIV Envelope Protein gp41; HIV Infections; HIV Integrase; HIV-1; Humans; Virus Internalization; Virus Replication
PubMed: 27357278
DOI: 10.1128/MMBR.00065-15 -
PloS One 2014A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the... (Meta-Analysis)
Meta-Analysis Review
48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis.
BACKGROUND
A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1-infected patients.
METHODS
A systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.
RESULTS
Thirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.
CONCLUSION
Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1-infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).
Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; HIV Infections; HIV-1; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Lipids; Lopinavir; Nitriles; Organophosphonates; Oxazines; Piperazines; Pyridones; Pyrimidines; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; Rilpivirine; Ritonavir; Tenofovir; Time Factors; Treatment Outcome; Viral Load
PubMed: 25188312
DOI: 10.1371/journal.pone.0105653 -
Frontiers in Immunology 2021HIV infection results in immune homeostasis perturbations, which is characterized by CD4 T-cell depletion, immune activation, and inflammation. Effective antiretroviral... (Meta-Analysis)
Meta-Analysis
HIV infection results in immune homeostasis perturbations, which is characterized by CD4 T-cell depletion, immune activation, and inflammation. Effective antiretroviral therapy (ART) does not fully restore immunologic and clinical health in people living with HIV (PLWH). Various drugs have been used to improve their immune status and CD4 T-cell counts, but no measures have been tested effective. Here we conduct a systematic review and meta-analysis of existing clinical studies on improving CD4 T-cell count while decreasing inflammation and immune activation. We retrieved possible relevant publications from a total of five electronic databases and selected eligible studies, which dealt with outcomes of medical therapy for CD4 T-cell count recovery, inflammation, and immune activation with or without ART. We paid particular attention to immunologic non-responders with a favorable treatment regimen. Thirty-three articles were included in the systematic review and meta-analysis. However, there were no safe and effective medications specific for improving CD4 T-cell reconstitution. The immunological benefits or adverse events mainly depend on the safety, dosage, and duration of the candidate medication use, as well as whether it is combined with ART. Under the "safe, combined, adequate and long (SCAL)" principles, alternative approaches are needed to accelerate the recovery of CD4 T-cells, and to prevent adverse long-term outcomes in PLWH with standard ART treatment.
Topics: CD4-Positive T-Lymphocytes; HIV Infections; HIV Long-Term Survivors; HIV-1; Humans; Immunity; Immunomodulation; Inflammation
PubMed: 33679779
DOI: 10.3389/fimmu.2021.632119 -
Virology Journal Jun 2023ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens.
METHODS
A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses.
RESULTS
We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease.
CONCLUSION
IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.
Topics: Adult; Humans; Zidovudine; Interferon-alpha; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Lymphoma
PubMed: 37287047
DOI: 10.1186/s12985-023-02077-0