-
PloS One 2014Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and therefore we evaluated this in comparison with the risk before HAART.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched Medline, Embase and ISI science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focussing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random effects model.
RESULTS
From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and 8 for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97-1.64) and 1.50 (95% CI 1.12-2.01) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0.004, I2 = 55.5). Pre-HAART pRRs were 1.26 (95% CI 1.11-1.43; P het = 0.82) and 1.28 (95% CI 1.10-1.49) among studies adjusted for ethnicity.
CONCLUSIONS
People with HIV/AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White skinned people with HIV/AIDS should be screened regularly and counselled against excessive sun exposure.
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antiretroviral Therapy, Highly Active; Black People; Female; HIV-1; Humans; Male; Melanoma; Middle Aged; Proportional Hazards Models; Risk; Skin Neoplasms; White People
PubMed: 24740329
DOI: 10.1371/journal.pone.0095096 -
PLoS Medicine Nov 2016Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.
METHODS AND FINDINGS
We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.
CONCLUSIONS
Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.
Topics: Anti-HIV Agents; Developed Countries; Developing Countries; HIV Infections; HIV-1; Humans; Medication Adherence
PubMed: 27898679
DOI: 10.1371/journal.pmed.1002183 -
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 -
Epidemiology (Cambridge, Mass.) Jan 2013Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings.
METHODS
We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses.
RESULTS
Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man).
CONCLUSIONS
ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.
Topics: Anti-HIV Agents; Developed Countries; Developing Countries; Female; HIV Infections; HIV-1; Heterosexuality; Humans; Male; Models, Statistical; Poisson Distribution; Regression Analysis
PubMed: 23222513
DOI: 10.1097/EDE.0b013e318276cad7 -
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 -
International Journal of Epidemiology Dec 2008The objective was to assess the risk of HIV transmission from orogenital intercourse (OI). (Review)
Review
BACKGROUND
The objective was to assess the risk of HIV transmission from orogenital intercourse (OI).
METHODS
Systematic review of the literature on HIV-1 infectiousness through OI conducted according to MOOSE guidelines for reviews of observational studies. The PubMed database and bibliographies of relevant articles were searched to July 2007.
RESULTS
Of the titles, 56 214 were searched from which 10 potentially appropriate studies were identified; two additional studies were identified through bibliographies and one through discussion with experts. There were 10 included studies, providing estimates of transmission probabilities per-partner (n = 5), incidence per-partner (n = 3), per-study participant (n = 3, following initially seronegative individuals whose partners are of unknown serostatus) and per-act (n = 3). Only four of 10 studies reported non-zero estimates: two per-partner estimates (20%, 95% CI: 6-51, n = 10 and a model-based estimate, 1%, range 0.85-2.3%), one per-study participant estimate (0.37%, 95% CI: 0.10-1.34%) and one per-act estimate (0.04%, 95% CI: 0.01-0.17%). Upper bounds for the 95% CI for zero estimates tended to be relatively large due to the small study sample sizes: 9.0, 12.1 and 2.8% for per-partner; 4.7, 9.6 and 1.8 per 100 person-years for incidence per-partner; 4.4% per-study participant and 0.45 and 0.02% for per-act. Given the small number of studies, a meta-analysis was not considered appropriate.
CONCLUSIONS
There are currently insufficient data to estimate precisely the risk from OI exposure. The low risk of transmission evident from identified studies means that more and larger studies would be required to provide sufficient evidence to derive more precise estimates.
Topics: Female; HIV Infections; HIV-1; Humans; Male; Probability; Sexual Behavior; Unsafe Sex
PubMed: 18664564
DOI: 10.1093/ije/dyn151 -
A systematic review of antiretroviral adherence interventions for HIV-infected people who use drugs.Current HIV/AIDS Reports Dec 2012HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of... (Review)
Review
HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provided significant improved short-term adherence and virologic outcomes, but these effects were not sustained after intervention cessation. Cohort and prospective studies suggested short-term increased cART adherence with MAT. More conclusive data regarding the efficacy on cART adherence and HIV treatment outcomes using cognitive behavioral therapy, motivational interviewing, peer-driven interventions and the integration of MAT into HIV clinical care are warranted. Of great concern was the virtual lack of interventions with sustained post-intervention adherence and virologic benefits. Future research directions, including the development of interventions that promote long-term improvements in adherence and virologic outcomes, are discussed.
Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Checklist; Drug Users; Female; HIV Seropositivity; HIV-1; Humans; Male; Medication Adherence; Patient Education as Topic; Randomized Controlled Trials as Topic; United States; Viral Load
PubMed: 22936463
DOI: 10.1007/s11904-012-0134-8 -
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 -
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