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Frontiers in Immunology 2021Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective...
Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective anti-HIV-1 vaccine. The major obstacle to the development of HIV-1 vaccine is the extreme diversity of viral genome sequences. Nonetheless, a number of broadly neutralizing antibodies (bNAbs) against HIV-1 have been made and identified in this area. Novel strategies based on using these bNAbs as an efficacious preventive and/or therapeutic intervention have been applied in clinical. In this review, we summarize the recent development of bNAbs and its application in HIV-1 acquisition prevention as well as discuss the innovative approaches being used to try to convey protection within individuals at risk and being treated for HIV-1 infection.
Topics: AIDS Vaccines; Animals; Antibody Specificity; Broadly Neutralizing Antibodies; Gene Transfer Techniques; Genes, env; Genetic Therapy; Genetic Variation; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunization, Passive; Models, Immunological; Vaccine Development; env Gene Products, Human Immunodeficiency Virus
PubMed: 34354709
DOI: 10.3389/fimmu.2021.697683 -
The Lancet. HIV Sep 2021Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts....
Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.
BACKGROUND
Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality.
METHODS
We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models.
FINDINGS
The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p=0·0076); the prevalence plateaued thereafter (p=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age.
INTERPRETATION
High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.
FUNDING
International Agency for Research on Cancer.
Topics: Age Factors; Anal Canal; HIV Infections; Humans; Male; Papillomaviridae; Papillomavirus Infections; Prevalence; Risk Factors; Sexuality; Squamous Intraepithelial Lesions
PubMed: 34339628
DOI: 10.1016/S2352-3018(21)00108-9 -
EClinicalMedicine May 2021Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This...
BACKGROUND
Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This study aimed to characterize HSV-2 epidemiology in this region.
METHODS
Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings up to August 23, 2020. Meta-analyses and meta-regressions were conducted.
FINDINGS
From 218 relevant publications, 451 overall outcome measures and 869 stratified measures were extracted. Pooled incidence rates ranged between 2.4-19.4 per 100 person-years across populations. Pooled seroprevalence was lowest at 37.3% (95% confidence interval (CI): 34.9-39.7%) in general populations and high in female sex workers and HIV-positive individuals at 62.5% (95% CI: 54.8-70.0%) and 71.3% (95% CI: 66.5-75.9%), respectively. In general populations, pooled seroprevalence increased steadily with age. Compared to women, men had a lower seroprevalence with an adjusted risk ratio (ARR) of 0.61 (95% CI: 0.56-0.67). Seroprevalence has decreased in recent decades with an ARR of 0.98 (95% CI: 0.97-0.99) per year. Seroprevalence was highest in Eastern and Southern Africa. Pooled HSV-2 proportion in genital ulcer disease was 50.7% (95% CI: 44.7-56.8%) and in genital herpes it was 97.3% (95% CI: 84.4-100%).
INTERPRETATION
Seroprevalence is declining by 2% per year, but a third of the population is infected. Age and geography play profound roles in HSV-2 epidemiology. Temporal declines and geographic distribution of HSV-2 seroprevalence mirror that of HIV prevalence, suggesting sexual risk behavior has been declining for three decades. HSV-2 is the etiological cause of half of genital ulcer disease and nearly all genital herpes cases with limited role for HSV-1.
FUNDING
This work was supported by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar and by the Qatar National Research Fund [NPRP 9-040-3-008].
PubMed: 34027335
DOI: 10.1016/j.eclinm.2021.100876 -
Southern African Journal of HIV Medicine 2021Persons living with human immunodeficiency virus (PLWH) constitute a vulnerable population in view of their impaired immune status. At this time, the full interaction... (Review)
Review
BACKGROUND
Persons living with human immunodeficiency virus (PLWH) constitute a vulnerable population in view of their impaired immune status. At this time, the full interaction between HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been incompletely described.
OBJECTIVE
The purpose of this study was to explore the impact of HIV and SARS-CoV-2 co-infection on mortality.
METHOD
We systematically searched PubMed and the Europe PMC databases up to 19 January 2021, using specific keywords related to our aims. All published articles on coronavirus disease 2019 (COVID-19) and HIV were retrieved. The quality of the studies was evaluated using the Newcastle-Ottawa Scale for observational studies. Statistical analysis was performed with Review Manager version 5.4 and Comprehensive Meta-Analysis version 3 software.
RESULTS
A total of 28 studies including 18 255 040 COVID-19 patients were assessed in this meta-analysis. Overall, HIV was associated with a higher mortality from COVID-19 on random-effects modelling {odds ratio [OR] = 1.19 [95% confidence interval (CI) = 1.01-1.39], = 0.03; = 72%}. Meta-regression confirmed that this association was not influenced by age ( = 0.208), CD4 cell count ( = 0.353) or the presence of antiretroviral therapy (ART) ( = 0.647). Further subgroup analysis indicated that the association was only statistically significant in studies from Africa (OR = 1.13, = 0.004) and the United States (OR = 1.30, = 0.006).
CONCLUSION
Whilst all persons ought to receive a SARS-CoV-2 vaccine, PLWH should be prioritised to minimise the risk of death because of COVID-19. The presence of HIV should be regarded as an important risk factor for future risk stratification of COVID-19.
PubMed: 33936793
DOI: 10.4102/sajhivmed.v22i1.1220 -
Frontiers in Pharmacology 2021: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors. : We searched studies...
: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors. : We searched studies written in English in PubMed, EMBASE, and Web of Science with no geographical or time restrictions. We evaluated the quality of the included literature. We calculated the pooled acceptability and performed meta-analysis of selected studies, including factors associated with the acceptability among MSM, using Review Manager (v5.3). : The acceptability among the 15 studies ( = 8,658) was 50% (95% CI: 0.27-0.72). The meta-analysis of seven articles ( = 4,200) indicated that having a college or higher degree (OR = 1.62, 95% CI: 1.35-1.95), disclosure of sexual orientation to healthcare professionals (HCPs; OR = 2.38, 95% CI: 1.47-3.86), vaccination with at least one dose for hepatitis A or B (OR = 2.10, 95% CI: 1.42-3.10), awareness of HPV (OR = 1.85, 95% CI: 1.21-2.83), knowledge of HPV (SMD = 0.28, 95% CI: 0.16-0.39), perceived susceptibility to HPV infection (SMD = 0.31, 95% CI: 0.11-0.50), and perceived severity of HPV-related disease (SMD = 0.40, 95% CI: 0.28-0.51) can promote acceptance of HPV vaccines. Meanwhile, people who have had unprotected anal sex or have more sex partners tend to have low acceptance of HPV vaccines. : HPV education should be actively promoted according to the factors that influence the acceptability of HPV vaccines among the MSM population. HPV education should be especially aimed at people with low academic qualifications and people with risky sexual behaviors, and should emphasize the aspects of susceptibility to and severity of HPV-related disease. More intervention trials should be conducted to increase the credibility of the results.
PubMed: 33867977
DOI: 10.3389/fphar.2021.600273 -
Scientific Reports Mar 2021Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis
Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05-1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21-2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.
Topics: COVID-19; Disease Susceptibility; HIV Infections; Humans; SARS-CoV-2
PubMed: 33737527
DOI: 10.1038/s41598-021-85359-3 -
Current HIV/AIDS Reports Apr 2021The relationship between antiretroviral therapy (ART) and cancer treatment outcomes among people living with HIV (PLWH) in low- and middle-income countries (LMICs) is... (Review)
Review
PURPOSE OF REVIEW
The relationship between antiretroviral therapy (ART) and cancer treatment outcomes among people living with HIV (PLWH) in low- and middle-income countries (LMICs) is complex and poorly understood for many cancers. We aimed to summarize existing evidence from LMICs regarding the benefit of ART on cancer treatment-related outcomes.
RECENT FINDINGS
We included twelve observational studies that reported associations between ART status and cancer treatment outcomes among HIV-positive patients in LMICs. Most confirmed ART was associated with improved cancer treatment outcomes. Heterogeneity in cancers under study, outcome measurement, categorization of ART status, and reporting of HIV-related immune function made formal comparison between studies untenable. Where evaluated, ART generally has a positive effect on cancer outcomes in people with HIV in LMICs. However, there remains a substantial gap in the literature regarding the impact of ART on treatment outcomes for most cancer types. Future research should focus on the optimal timing and integration of ART and cancer treatment for PLWH with strategies applicable to constrained-resource settings.
Topics: Anti-HIV Agents; Developing Countries; HIV Infections; Humans; Neoplasms; Poverty; Treatment Outcome
PubMed: 33528741
DOI: 10.1007/s11904-021-00542-5 -
Clinical Microbiology and Infection :... Apr 2021While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates...
BACKGROUND
While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.
OBJECTIVES
To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19.
DATA SOURCES
PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv.
STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS
All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.
INTERVENTIONS
PrEP and PEP candidate for COVID-19.
METHODS
Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion.
RESULTS
We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements.
CONCLUSIONS
The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antimalarials; Antiviral Agents; COVID-19; Humans; Hydroxychloroquine; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; SARS-CoV-2; Vaccines
PubMed: 33476807
DOI: 10.1016/j.cmi.2021.01.013 -
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 -
AIDS Reviews Oct 2020Antiretroviral therapy (ART) inhibits HIV replication but does not eradicate the latent reservoir. The previous research suggests that earlier ART initiation provides...
Antiretroviral therapy (ART) inhibits HIV replication but does not eradicate the latent reservoir. The previous research suggests that earlier ART initiation provides benefit on limiting reservoir size, but timing and extent of this effect remain unclear. Analytic treatment interruption (ATI) may be used to demonstrate HIV remission, but whether early ART also improves likelihood or duration of even temporary virologic remission is unclear. This review seeks to answer both questions. We performed a systematic review and analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and included 21 interventional or observational studies with sufficient HIV reservoir outcomes. We also aggregated reservoir outcomes and transformed data into approximate measurements of total HIV DNA per million peripheral blood mononuclear cells and analyzed the correlation between timing of ART initiation and reservoir size. People living with HIV who initiate ART in primary infection maintain smaller reservoirs on suppressive ART than those who initiate treatment during chronic infection. The reduction of reservoir is most pronounced when ART is started within 2 weeks of HIV acquisition. Across studies, we found a moderately strong association between longer time to ART initiation and reservoir size, which was strongest when measured after 1 year on ART (Pearson's r = 0.69, p = 0.0003). After ATI, larger pre-ATI reservoir size predicts shorter time to viral rebound. Early ART may also facilitate long-term control of viremia. Although achieving sustained HIV remission will require further interventions, initiating ART very early in infection could limit the extent of the reservoir and also lead to post-ATI control in rare cases.
Topics: Anti-Retroviral Agents; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Viral Load; Virus Latency
PubMed: 33105471
DOI: 10.24875/AIDSRev.20000001