-
PloS One 2015Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral... (Review)
Review
BACKGROUND
Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration.
METHODS AND FINDINGS
Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained.
CONCLUSIONS
A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
Topics: Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV Infections; HIV-1; Humans; MEDLINE; Sensitivity and Specificity
PubMed: 25790185
DOI: 10.1371/journal.pone.0115019 -
Journal of the International AIDS... Jun 2018Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of... (Meta-Analysis)
Meta-Analysis
Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status.
INTRODUCTION
Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.
METHODS
We performed meta-analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random-effect models. I statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.
RESULTS AND DISCUSSION
In review 1, 37 publications (25 independent studies) were included in the meta-analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high-risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta-analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.
CONCLUSIONS
These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.
Topics: Female; HIV Infections; Humans; Incidence; Longitudinal Studies; Male; Papillomavirus Infections; Papillomavirus Vaccines; Pregnancy; Vaccination
PubMed: 29873885
DOI: 10.1002/jia2.25110 -
International Journal of Medical... Jan 2021Orientia tsutsugamushi (OT), the causative agent of the vector-borne Scrub typhus zoonotic disease in humans, is a unique microorganism that exists in the Asia-Pacific...
Orientia tsutsugamushi (OT), the causative agent of the vector-borne Scrub typhus zoonotic disease in humans, is a unique microorganism that exists in the Asia-Pacific region since a long time. In spite of its occurrence, the organism had been neglected until recent years. Humans are the accidental dead-end hosts of O. tsutsugamushi and display manifestations which are both severe and misleading. The vast antigenic diversity of OT and non-pathognomic symptoms of Scrub typhus, create hurdles in the clinical management of the disease and impede the OT-research. Many countries in the Asia-Pacific region have reported the resurgence of OT- infections and have raised concerns for its expanding distribution. This has triggered the development of advanced techniques for diagnosis and research on exploring a successful vaccine candidate to reduce the burden of the disease. Thus, the aim of this systematic review is to provide an update on the recent advances in the OT-research and highlight the key areas that have remained obscure and demand attention.
Topics: Antigenic Variation; Asia; Humans; Orientia tsutsugamushi; Scrub Typhus
PubMed: 33338890
DOI: 10.1016/j.ijmm.2020.151467 -
PloS One 2019Point of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically...
BACKGROUND
Point of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS.
METHODS
Studies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective.
RESULTS
197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV-1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV-1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV-1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing.
CONCLUSIONS
Performance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed.
Topics: Age Factors; HIV Infections; HIV-1; Humans; Point-of-Care Systems; Point-of-Care Testing; Polymerase Chain Reaction; RNA, Viral; Reproducibility of Results; Sensitivity and Specificity; Viral Load
PubMed: 31246963
DOI: 10.1371/journal.pone.0218369 -
Journal of the International AIDS... Oct 2020Screening for acute and early HIV infections (AEHI) among men who have sex with men (MSM) remains uncommon in sub-Saharan Africa (SSA). Yet, undiagnosed AEHI among MSM...
INTRODUCTION
Screening for acute and early HIV infections (AEHI) among men who have sex with men (MSM) remains uncommon in sub-Saharan Africa (SSA). Yet, undiagnosed AEHI among MSM and subsequent failure to link to care are important drivers of the HIV epidemic. We conducted a systematic review and meta-analysis of AEHI yield among MSM mobilized for AEHI testing; and assessed which risk factors and/or symptoms could increase AEHI yield in MSM.
METHODS
We systematically searched four databases from their inception through May 2020 for studies reporting strategies of mobilizing MSM for testing and their AEHI yield, or risk and/or symptom scores targeting AEHI screening. AEHI yield was defined as the proportion of AEHI cases among the total number of visits. Study estimates for AEHI yield were pooled using random effects models. Predictive ability of risk and/or symptom scores was expressed as the area under the receiver operator curve (AUC).
RESULTS
Twenty-two studies were identified and included a variety of mobilization strategies (eight studies) and risk and/or symptom scores (fourteen studies). The overall pooled AEHI yield was 6.3% (95% CI, 2.1 to 12.4; I = 94.9%; five studies); yield varied between studies using targeted strategies (11.1%; 95% CI, 5.9 to 17.6; I = 83.8%; three studies) versus universal testing (1.6%; 95% CI, 0.8 to 2.4; two studies). The AUC of risk and/or symptom scores ranged from 0.69 to 0.89 in development study samples, and from 0.51 to 0.88 in validation study samples. AUC was the highest for scores including symptoms, such as diarrhoea, fever and fatigue. Key risk score variables were age, number of sexual partners, condomless receptive anal intercourse, sexual intercourse with a person living with HIV, a sexually transmitted infection, and illicit drug use. No studies were identified that assessed AEHI yield among MSM in SSA and risk and/or symptom scores developed among MSM in SSA lacked validation.
CONCLUSIONS
Strategies mobilizing MSM for targeted AEHI testing resulted in substantially higher AEHI yields than universal AEHI testing. Targeted AEHI testing may be optimized using risk and/or symptom scores, especially if scores include symptoms. Studies assessing AEHI yield and validation of risk and/or symptom scores among MSM in SSA are urgently needed.
Topics: Africa South of the Sahara; Coitus; HIV Infections; Homosexuality, Male; Humans; Male; Mass Screening; Risk Factors; Sexual and Gender Minorities
PubMed: 33000916
DOI: 10.1002/jia2.25590 -
PloS One 2019Adolescents aged 10-19 represent one sixth of the world's population and have a high burden of morbidity, particularly in low-resource settings. We know little about the...
BACKGROUND
Adolescents aged 10-19 represent one sixth of the world's population and have a high burden of morbidity, particularly in low-resource settings. We know little about the potential of community-based peer facilitators to improve adolescent health in such contexts.
METHODS
We did a systematic review of peer-facilitated community-based interventions for adolescent health in low- and middle-income countries (LMICs). We searched databases for randomised controlled trials of interventions featuring peer education, counselling, activism, and/or outreach facilitated by young people aged 10-24. We included trials with outcomes across key areas of adolescent health: infectious and vaccine preventable diseases, undernutrition, HIV/AIDS, sexual and reproductive health, unintentional injuries, violence, physical disorders, mental disorders and substance use. We summarised evidence from these trials narratively. PROSPERO registration: CRD42016039190.
RESULTS
We found 20 studies (61,014 adolescents). Fourteen studies tested interventions linked to schools or colleges, and 12 had non-peer-facilitated components, e.g. health worker training. Four studies had HIV-related outcomes, but none reported reductions in HIV prevalence or incidence. Nine studies had clinical sexual and reproductive health outcomes, but only one reported a positive effect: a reduction in Herpes Simplex Virus-2 incidence. Three studies had violence-related outcomes, two of which reported reductions in physical violence by school staff and perpetration of physical violence by adolescents. Seven studies had mental health outcomes, four of which reported reductions in depressive symptoms. Finally, we found eight studies on substance use, four of which reported reductions in alcohol consumption and smoking or tobacco use. There were no studies on infectious and vaccine preventable diseases, undernutrition, or injuries.
CONCLUSIONS
There are few trials on the effects of peer-facilitated community-based interventions for adolescent health in LMICs. Existing trials have mixed results, with the most promising evidence supporting work with peer facilitators to improve adolescent mental health and reduce substance use and violence.
Topics: Adolescent; Adolescent Health; Bias; Community Health Services; Developing Countries; Health Services Needs and Demand; Humans; Income; Outcome Assessment, Health Care; Peer Group
PubMed: 30673732
DOI: 10.1371/journal.pone.0210468 -
Human Vaccines & Immunotherapeutics Nov 2022COVID-19 vaccines emerged as a worldwide hope to contain the pandemic. However, many people are still hesitant to receive these vaccines. We aimed to systematically...
INTRODUCTION
COVID-19 vaccines emerged as a worldwide hope to contain the pandemic. However, many people are still hesitant to receive these vaccines. We aimed to systematically review the public knowledge, perception, and acceptability of COVID-19 vaccines in the Middle East and North Africa (MENA) countries and the predictors of vaccine acceptability in this region.
METHODS
We systematically searched databases of PubMed, Scopus, Web of Science, and Cochrane and retrieved all relevant studies by 5 August 2021.
RESULTS
There was a considerable variation in the COVID-19 vaccine acceptance rates, from 12% in a study from Israel to 83.3% in Kuwait, although two other studies from Israel mentioned 75% and 82.2% acceptability rates. Concerns about the side effects and safety of the vaccine were the main reasons for the lack of acceptability of taking the vaccine, which was reported in 19 studies. .
CONCLUSION
Several factors, such as age, gender, education level, and comorbidities, are worthy of attention as they could expand vaccine coverage in the target population..
Topics: Africa, Northern; COVID-19; COVID-19 Vaccines; Humans; Middle East; Pandemics
PubMed: 35318872
DOI: 10.1080/21645515.2022.2043719 -
The Lancet Regional Health. Europe Feb 2023Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe...
BACKGROUND
Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2's contribution to HIV transmission were also reviewed.
METHODS
Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted.
FINDINGS
211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI: 11.5-13.3%) among general populations, 27.8% (95% CI: 17.5-39.4%) among men who have sex with men, 46.0% (95% CI: 40.1-51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI: 55.5-70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI: 0.58-0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI: 15.3-29.6%) and 66.0% (95% CI: 62.9-69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI: 1.10-1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend.
INTERPRETATION
Although seroprevalence is declining, a significant proportion of Europe's population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services.
FUNDING
Qatar National Research Fund [NPRP 9-040-3-008] and pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar supported this study.
PubMed: 36818238
DOI: 10.1016/j.lanepe.2022.100558 -
Journal of the International AIDS... Jan 2017HIV is transmitted more effectively during anal intercourse (AI) than vaginal intercourse (VI). However, patterns of heterosexual AI practice and its contribution to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HIV is transmitted more effectively during anal intercourse (AI) than vaginal intercourse (VI). However, patterns of heterosexual AI practice and its contribution to South Africa's generalized epidemic remain unclear. We aimed to determine how common and frequent heterosexual AI is in South Africa.
METHODS
We searched for studies reporting the proportion practising heterosexual AI (prevalence) and/or the number of AI and unprotected AI (UAI) acts (frequency) in South Africa from 1990 to 2015. Stratified random-effects meta-analysis by sub-groups was used to produce pooled estimates and assess the influence of participant and study characteristics on AI prevalence. We also estimated the fraction of all sex acts which were AI or UAI and compared condom use during VI and AI.
RESULTS
Of 41 included studies, 31 reported on AI prevalence and 14 on frequency, over various recall periods. AI prevalence was high across different recall periods for sexually active general-risk populations (e.g. lifetime = 18.4% [95%CI:9.4-27.5%], three-month = 20.3% [6.1-34.7%]), but tended to be even higher in higher-risk populations such as STI patients and female sex workers (e.g. lifetime = 23.2% [0.0-47.4%], recall period not stated = 40.1% [36.2-44.0%]). Prevalence was higher in studies using more confidential interview methods. Among general and higher-risk populations, 1.2-40.0% and 0.7-21.0% of all unprotected sex acts were UAI, respectively. AI acts were as likely to be condom protected as vaginal acts.
CONCLUSION
Reported heterosexual AI is common but variable among South Africans. Nationally and regionally representative sexual behaviour studies that use standardized recall periods and confidential interview methods, to aid comparison across studies and minimize reporting bias, are needed. Such data could be used to estimate the extent to which AI contributes to South Africa's HIV epidemic.
Topics: Adult; Anal Canal; Black People; Condoms; Female; HIV Infections; Heterosexuality; Humans; Male; Prevalence; Safe Sex; Sex Workers; Sexual Behavior; South Africa; Unsafe Sex
PubMed: 28364565
DOI: 10.7448/IAS.20.1.21162 -
Open Forum Infectious Diseases Jun 2019Registration of interventional trials of Food and Drug Administration-regulated drug and biological products and devices became a legal requirement in 2007; the vast...
BACKGROUND
Registration of interventional trials of Food and Drug Administration-regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research.
METHODS
Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007-2017, ID trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials.
RESULTS
ID-related trials represented 6.9%-9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak.
CONCLUSIONS
This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.
PubMed: 31276007
DOI: 10.1093/ofid/ofz189