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The Lancet. Infectious Diseases Jul 2011Despite recent changes in the epidemiology of HIV infection and malaria and major improvements in their control, these diseases remain two of the most important... (Review)
Review
Despite recent changes in the epidemiology of HIV infection and malaria and major improvements in their control, these diseases remain two of the most important infectious diseases and global health priorities. As they have overlapping distribution in tropical areas, particularly sub-Saharan Africa, any of their clinical, diagnostic, and therapeutic interactions might have important effects on patient care and public health policy. The biological basis of these interactions is well established. HIV infection induces cellular depletion and early abnormalities of CD4+ T cells, decreases CD8+ T-cell counts and function (cellular immunity), causes deterioration of specific antigen responses (humoral immunity), and leads to alteration of innate immunity through impairment of cytolytic activity and cytokine production by natural killer cells. Therefore, HIV infection affects the immune response to malaria, particularly premunition in adolescents and adults, and pregnancy-specific immunity, leading to different patterns of disease in HIV-infected patients compared with HIV-uninfected patients. In this systematic review, we collate data on the effects of HIV on malaria and discuss their therapeutic consequences. HIV infection is associated with increased prevalence and severity of clinical malaria and impaired response to antimalarial treatment, depending on age, immunodepression, and previous immunity to malaria. HIV also affects pregnancy-specific immunity to malaria and response to intermittent preventive treatment. Co-trimoxazole (trimethoprim-sulfamethoxazole) prophylaxis and antiretroviral treatment reduce occurrence of clinical malaria; however, these therapies interact with antimalarial drugs, and new therapeutic guidelines are needed for concomitant use.
Topics: Adolescent; Adult; Africa South of the Sahara; Anti-HIV Agents; Antimalarials; Female; HIV; HIV Infections; Humans; Malaria; Male; Plasmodium; Pregnancy
PubMed: 21700241
DOI: 10.1016/S1473-3099(11)70031-7 -
Survey of Ophthalmology 2022Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.
Topics: Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Ganciclovir; Glaucoma; Humans; Inflammation; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 34954093
DOI: 10.1016/j.survophthal.2021.12.006 -
AIDS (London, England) Jan 2014To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to cART.
METHODS
Systematic review and meta-analysis of studies reporting HIV RNA and CD4 cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible.
RESULTS
Twenty-five eligible cohort studies reported data on 49 578 (range 42-15 646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4 cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86-1.29) at 1-4 months, 0.91 (0.83-1.00) at 6 months, 0.99 (0.94-1.05) at 11-12 months, and 0.99 (0.77-1.28) at 18-48 months. The overall RRRE at 1-48 months was 0.97 (95% confidence interval 0.92-1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 cell count gain between those receiving vs. not receiving TB treatment ranged from -10 to 60 cells/μl (median 27) by 6 months (seven estimates) and -10 to 29 (median 6) by 11-12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis.
CONCLUSION
Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Plasma; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24072197
DOI: 10.1097/01.aids.0000434936.57880.cd -
Seminars in Liver Disease May 2022Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination... (Review)
Review
Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had "low" microelimination scores, 11 had "high" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Sustained Virologic Response
PubMed: 35189667
DOI: 10.1055/a-1777-6112 -
Clinical Infectious Diseases : An... Mar 2016Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR.
METHODS
A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected "low-risk" patients; (2) Mono-HCV infected "high-risk" patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.
RESULTS
In the 43 studies of HCV mono-infected "low-risk" patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71-3.35; I(2) = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%-1.69%). For the 14 studies of HCV monoinfected "high-risk" patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07-33.46; I(2) = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%-15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00-123.49; I(2) = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%-48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.
CONCLUSIONS
SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.
Topics: Adolescent; Adult; Antiviral Agents; Coinfection; Drug Users; Female; Follow-Up Studies; HIV Infections; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Male; RNA, Viral; Recurrence; Ribavirin; Risk Factors; Sustained Virologic Response; Viral Load; Young Adult
PubMed: 26787172
DOI: 10.1093/cid/civ948 -
Alimentary Pharmacology & Therapeutics Mar 2018Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust... (Meta-Analysis)
Meta-Analysis
Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia.
BACKGROUND
Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real-world evidence of interferon (IFN)-free DAA treatment for HCV GT1-infected patients in Asia is still lacking.
AIM
To systematically review and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for HCV GT1 infection in Asia.
METHODS
We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN-free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a random-effects model. Subgroup analysis and meta-regression as previously registered in PROSPERO were performed to determine how pre-planned variables might have affected the pooled estimates.
RESULTS
We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6-91.1, I = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001).
CONCLUSION
All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end-stage renal disease.
Topics: Adult; Antiviral Agents; Asia; Drug Therapy, Combination; General Practice; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Treatment Outcome
PubMed: 29327780
DOI: 10.1111/apt.14507 -
Neurology Jan 2014Interferon-β (IFN-β) has been shown to reduce relapse rates in multiple sclerosis; however, the clinical response appears to vary among individuals. Can early MRI be... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Interferon-β (IFN-β) has been shown to reduce relapse rates in multiple sclerosis; however, the clinical response appears to vary among individuals. Can early MRI be used to identify those patients who have a poor response to treatment?
METHODS
A systematic review of studies examining differential treatment response and clinical endpoints in groups defined as responders or nonresponders to IFN-β was performed. Meta-analytic techniques were used to combine study results where appropriate.
RESULTS
Patients with MRI evidence of poor response to IFN-β treatment as defined by either ≥2 new hyperintense T2 lesions or new gadolinium-enhancing lesions had significantly increased risk of both future relapses and progression as defined by the Expanded Disability Status Scale. There appeared to be an increased risk of poor outcomes 16 years after treatment initiation in those with an initial poor response to treatment. Previous evidence has shown this not to be the case in placebo arms of clinical trials.
CONCLUSIONS
For those patients starting IFN-β, early MRI, within 6 to 24 months after starting treatment, has the potential to provide important information when counseling patients about the likelihood of future treatment failure. This can inform treatment decisions before clinical relapses or disease progression.
Topics: Clinical Trials as Topic; Humans; Interferon-beta; Magnetic Resonance Imaging; Multiple Sclerosis; Predictive Value of Tests; Treatment Failure
PubMed: 24336144
DOI: 10.1212/WNL.0000000000000036 -
AIDS and Behavior Mar 2017Although an increasing number of HIV infected people are accessing antiretroviral treatment, many do not achieve complete HIV viral suppression and remain at risk for... (Comparative Study)
Comparative Study Meta-Analysis Review
Although an increasing number of HIV infected people are accessing antiretroviral treatment, many do not achieve complete HIV viral suppression and remain at risk for AIDS and capable of HIV transmission. Food insecurity has been identified as a potential risk factor for poor virologic response, but the association between these factors has been inconsistently documented in the literature. We systematically searched five electronic databases and bibliographies of relevant studies through April 2015 and retrieved 11 studies that met our inclusion criteria, of which nine studies were conducted in North America and the remaining two studies were in Brazil and Uganda respectively. Meta-analyzed results indicated that experiencing food insecurity resulted in 29% lower odds of achieving complete HIV viral suppression (OR = 0.71, 95% CI 0.61-0.82) and this significant inverse association was consistently found regardless of study design, exposure measurement, and confounder adjustment methods. These findings suggest that food insecurity is a potential risk factor for incomplete HIV viral suppression in people living with HIV.
Topics: Anti-HIV Agents; Brazil; Cross-Cultural Comparison; Food Supply; HIV Infections; HIV-1; Humans; North America; Statistics as Topic; Uganda
PubMed: 27837425
DOI: 10.1007/s10461-016-1605-5 -
Expert Opinion on Pharmacotherapy Mar 2010Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when... (Review)
Review
IMPORTANCE OF THE FIELD
Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation.
AREAS COVERED IN THIS REVIEW
Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted.
WHAT THE READER WILL GAIN
To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials.
TAKE HOME MESSAGE
Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.
Topics: Administration, Oral; Anemia, Hemolytic; Antiviral Agents; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Polyethylene Glycols; RNA, Viral; Recombinant Proteins; Ribavirin; Treatment Outcome; Viral Load
PubMed: 20163278
DOI: 10.1517/14656560903580001 -
Health Technology Assessment... May 2016Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.
OBJECTIVES
To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza.
METHODS
We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.
RESULTS
Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).
CONCLUSIONS
Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002245.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Antiviral Agents; Asthma; Child; Dose-Response Relationship, Drug; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Neuraminidase; Oseltamivir; Randomized Controlled Trials as Topic; Zanamivir
PubMed: 27246259
DOI: 10.3310/hta20420