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International Journal of Infectious... May 2016People who inject drugs are at high risk of HIV infection but often face barriers in accessing medical care including access to antiretroviral therapy (ART). Evidence is... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
People who inject drugs are at high risk of HIV infection but often face barriers in accessing medical care including access to antiretroviral therapy (ART). Evidence is available about the effectiveness of opioid agonist therapy on drug dependency and risk behaviors. However, it remains scattered regarding access to ART among HIV-positive people who inject drugs. We conducted a systematic review to examine the association of opioid agonist therapy with ART initiation among HIV-positive people who inject drugs.
METHODS
We searched the literature for evidence from seven databases. We conducted a narrative synthesis and meta-analysis to examine the association of opioid agonist therapy with ART initiation.
RESULTS
Five out of 2,901 identified studies met the inclusion criteria. Three out of five studies reported that, HIV-positive people receiving opioid agonist therapy initiated ART more than those not receiving opioid agonist therapy. In meta-analysis, opioid agonist therapy was associated with ART initiation among HIV positive people who inject drugs (pooled odds ratio: 1.68; 95% confidence interval: 1.03-2.73).
CONCLUSIONS
Opioid agonist therapy is positively associated with ART initiation among HIV-positive people who inject drugs. It is important to scale up opioid agonist therapy among people who inject drugs to improve their ART initiation.
Topics: Analgesics, Opioid; Anti-Retroviral Agents; Drug Users; HIV Infections; HIV Seropositivity; Humans; Medication Adherence; Opioid-Related Disorders; Substance Abuse, Intravenous
PubMed: 27044520
DOI: 10.1016/j.ijid.2016.03.022 -
Tropical Medicine & International... Feb 2015To assess whether pregnancy accelerates HIV disease progression. (Review)
Review
OBJECTIVE
To assess whether pregnancy accelerates HIV disease progression.
METHODS
Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability.
RESULTS
15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95% CI: 0.74-1.25) or mortality (summary RR: 0.97, 95% CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95% CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95% CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions.
CONCLUSIONS
In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so.
Topics: Adolescent; Adult; Anti-HIV Agents; Disease Progression; Female; HIV Infections; Humans; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Young Adult
PubMed: 25358498
DOI: 10.1111/tmi.12412 -
Journal of Medical Virology Oct 2022Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside... (Meta-Analysis)
Meta-Analysis Review
Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ test) and I statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4 counts < 350 cell/mm , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.
Topics: Adult; Anti-HIV Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV Infections; HIV Protease Inhibitors; Humans; Interleukin-6; Protease Inhibitors; Ritonavir; Viral Load
PubMed: 35665943
DOI: 10.1002/jmv.27912 -
Journal of the International AIDS... Jul 2021HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis.
METHODS
We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS-defining events. We pooled effect estimates using random effects meta-analysis.
RESULTS AND DISCUSSION
We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] -2% to +1%). Among people with CD4 count ≤50 cells/mm , earlier ART (≤4 weeks) reduced risk of death (RD -6%, -10% to -1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS-defining events (RD -2%, 95% CI -4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens.
DISCUSSION
Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART.
Topics: Anti-HIV Agents; CD4 Lymphocyte Count; Coinfection; Female; HIV Infections; Humans; Pregnancy; Tuberculosis
PubMed: 34289243
DOI: 10.1002/jia2.25772 -
Journal of the International AIDS... 2015The effectiveness of antiretroviral therapy (ART) is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effectiveness of antiretroviral therapy (ART) is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4 cell count measures in patients who are virologically suppressed.
METHODS
We systematically searched three databases and two conference sites up to 31 October 2014 for studies reporting CD4 changes among patients who were on ART and virologically suppressed. No geographic, language or age restrictions were applied.
RESULTS AND DISCUSSION
We identified 12 published and 1 unpublished study reporting CD4 changes among 20,297 virologically suppressed patients. The pooled proportion of patients who experienced an unexplained, confirmed CD4 decline was 0.4% (95% CI 0.2-0.6%). Results were not influenced by duration of follow-up, age, study design or region of economic development. No studies described clinical adverse events among virologically suppressed patients who experienced CD4 declines.
CONCLUSIONS
The findings of this review support reducing or stopping routine CD4 monitoring for patients who are immunologically stable on ART in settings where routine viral load monitoring is provided.
Topics: Anti-HIV Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Male; Viral Load
PubMed: 26257204
DOI: 10.7448/IAS.18.1.20061 -
The Journal of Antimicrobial... Dec 2014The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness and safety of abacavir/lamivudine and tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have reviewed the available evidence.
DESIGN
Systematic review and meta-analysis of RCTs using standard Cochrane Collaboration methodologies.
METHODS
We calculated risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks. Where available, results were analysed according to VL screening levels (<100,000 or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and meta-regression.
RESULTS
Meta-analytical pooling of RCTs with a direct comparison of abacavir/lamivudine and tenofovir/emtricitabine according to baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions of subjects with VL <50 copies/mL were similar in the overall comparison (RR 0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99-1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta-regression analysis at 48 weeks confirms the results of subgroup analysis. Similar virological results were found at 96 weeks (four trials, 2003 patients). Differences in the occurrence of adverse events requiring discontinuation of treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this difference, mostly related to suspected abacavir hypersensitivity reaction, was not statistically significant.
CONCLUSIONS
Our cumulative, cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL.
Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Dideoxynucleosides; Emtricitabine; HIV Infections; Humans; Lamivudine; Organophosphonates; Randomized Controlled Trials as Topic; Tenofovir; Treatment Outcome
PubMed: 25074854
DOI: 10.1093/jac/dku279 -
Clinical Infectious Diseases : An... Jun 2015This systematic review aimed to assess the safety and efficacy of antiretroviral options for postexposure prophylaxis (PEP). Recognizing the limited data on the safety... (Review)
Review
BACKGROUND
This systematic review aimed to assess the safety and efficacy of antiretroviral options for postexposure prophylaxis (PEP). Recognizing the limited data on the safety and efficacy of antiretroviral drugs for PEP in children, this review was extended to include consideration of data on the use of antiretroviral drugs for treatment of infants and children living with human immunodeficiency virus.
METHODS
The PEP literature was assessed to identify studies reporting safety and completion rates for children given PEP, and this information was complemented by safety and efficacy data for drugs used in antiretroviral therapy. The proportion of patients experiencing each outcome was calculated and data were pooled using random-effects meta-analysis.
RESULTS
Three prospective cohort studies reported outcomes of children given zidovudine (ZDV) plus lamivudine (3TC) as a 2-drug PEP regimen. The proportion of children completing the full 28-day course of PEP was 64.0% (95% confidence interval [CI], 41.2%-86.8%), whereas the proportion discontinuing due to adverse events was 4.5% (95% CI, .4%-8.6%). One randomized trial compared abacavir (ABC) plus lamivudine (3TC) and ZDV+3TC as part of a dual or triple first-line antiretroviral therapy regimen; this study showed better efficacy in the ABC-containing combinations and no difference in the time to first serious adverse event. Three randomized trials compared lopinavir/ritonavir (LPV/r) to nevirapine (NVP) for antiretroviral therapy and showed a lower risk of treatment discontinuations associated with LPV/r vs NVP (hazard ratio, 0.56 [95% CI, .41-.75]) but no difference in drug-related adverse events. The overall quality of the evidence was rated as very low.
CONCLUSIONS
This review supports ZDV+3TC+LPV/r as the preferred 3-drug regimen for PEP in children.
Topics: Anti-HIV Agents; Child; Child, Preschool; Cohort Studies; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Lamivudine; Lopinavir; Nevirapine; Post-Exposure Prophylaxis; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Ritonavir; Zidovudine
PubMed: 25972500
DOI: 10.1093/cid/civ110 -
International Journal of Antimicrobial... Nov 2019Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human... (Meta-Analysis)
Meta-Analysis Review
Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. A meta-analysis of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients was performed. Odds ratios (ORs) of efficacy outcome data favouring INSTI use in different clinical settings demonstrated that INSTIs have higher efficacy compared with drugs of other classes. For combination antiretroviral therapy-naïve patients and virologically-suppressed patients who switched to INSTI-based therapy, the OR was 1.484 (95% CI 1.229-1.790) and 1.341 (95% CI 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virological failure than to non-INSTIs (OR = 0.081, 95% CI 0.004-1.849), whereas the opposite was observed for raltegravir (RAL) (OR = 3.137, 95% CI 1.827-5.385) and elvitegravir (EVG) (OR = 1.886, 95% CI 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir was rare, whereas EVG and RAL had low genetic barriers to resistance and the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring the emergence of resistance to INSTIs and the development of drugs with high genetic barriers are clear paths for future research.
Topics: Amides; Drug Resistance, Viral; HIV Infections; HIV Integrase; HIV Integrase Inhibitors; HIV-1; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, 4 or More Rings; Humans; Microbial Sensitivity Tests; Oxazines; Piperazines; Pyridones; Quinolones; Raltegravir Potassium; Virus Replication
PubMed: 31398480
DOI: 10.1016/j.ijantimicag.2019.08.008 -
PloS One 2023HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally.
METHODS
This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran's Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis.
RESULTS
Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7-42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2-46.4%) than female (36.5%, 95% CI: 26.9-50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%).
CONCLUSIONS
Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation.
Topics: Adult; Female; Humans; Male; Anti-HIV Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV Infections; Prevalence
PubMed: 37874794
DOI: 10.1371/journal.pone.0286476 -
Journal of Acquired Immune Deficiency... Aug 2016Youth living with HIV are highly under-represented in the evidence base for adherence interventions, despite their diverse and unique needs and barriers. (Review)
Review
INTRODUCTION
Youth living with HIV are highly under-represented in the evidence base for adherence interventions, despite their diverse and unique needs and barriers.
OBJECTIVE
This systematic review aimed to identify antiretroviral therapy (ART) adherence interventions specifically targeting adolescents and young adults (defined as ages 13-24) with the goal of characterizing the evidence base.
METHODS
Articles were identified using the PubMed database and cover work published through September 14, 2015.
INCLUSION CRITERIA
(1) average age 13 to 24, (2) HIV positive, (3) on or beginning ART, (4) intervention targeted ART adherence in full or in part, (5) reported adherence, viral load, and/or CD4 count outcomes. Strength of evidence was defined as level 1 [randomized controlled trial (RCT) with significance testing on outcomes], 2 (within group studies with statistical testing on outcomes), 3 (RCTs with descriptive results), or 4 (within group studies with descriptive results).
RESULTS
Of 151 articles, 10 met inclusion criteria. Published between 2003 and 2014, these studies evaluated diverse intervention approaches. Most were conducted in the US and were small pilots that have yet to be replicated despite promising results. Only 3 studies met criteria for highest level strength of evidence; 2 supported a phone-based counseling approach with adherence monitors and 1 for weekly individual and family counseling.
CONCLUSIONS
Despite nearly 20 years passing since the wide-scale availability of ART, and clear recognition that adolescents and youth adults fair worse on the cascade of HIV care, the evidence base remains sparse and underdeveloped. Promising approaches need replication and more rigorous studies are desperately needed.
Topics: Adolescent; Adolescent Behavior; Adolescent Health Services; Anti-HIV Agents; CD4 Lymphocyte Count; Evidence-Based Practice; HIV Infections; Health Promotion; Healthcare Disparities; Humans; Medication Adherence; Social Stigma; Viral Load; Young Adult
PubMed: 26959190
DOI: 10.1097/QAI.0000000000000977