•HIV and malaria remain important concerns with major global health implications.•Co-infection can cause hematologic abnormalities and greater morbidity in Africa.•The prevalence of asymptomatic ...malaria was highest in Uganda and Western Kenya.•Asymptomatic malaria was common and impacted hematologic parameters.•Anemia was more likely among people living with HIV.
HIV and malaria coinfection impacts disease management and clinical outcomes. This study investigated hematologic abnormalities in malaria-asymptomatic people living with HIV (PLHIV) in regions with differing malaria transmission.
Study participants were enrolled in the African Cohort Study: two sites in Kenya, one in Uganda, and one in Nigeria. Data was collected at enrollment and every 6 months. Logistic regression estimated odds ratios for associations between HIV/malaria status and anemia, thrombocytopenia, and leucopenia.
Samples from 1587 participants with one or more visits comprising 1471 (92.7%) from PLHIV and 116 (7.3%) without HIV were analyzed. Parasite point prevalence significantly differed across the study sites (P <0.001). PLHIV had higher odds of anemia, with males at lower odds compared to females; the odds of anemia decreased with age, reaching significance in those ≥50 years old. Participants in Kisumu, Kenya had higher odds of anemia compared to other sites. PLHIV had higher odds of leucopenia, but malaria co-infection was not associated with worsened leucopenia. The odds of thrombocytopenia were decreased in HIV/malaria co-infection compared to the uninfected group.
Hematological parameters are important indicators of health and disease. In PLHIV with asymptomatic malaria co-infection enrolled across four geographic sites in three African countries, abnormalities in hematologic parameters differ in different malaria transmission settings and are region-specific.
Men who have sex with men (MSM) living with HIV are at increased risk for anal cancer. We evaluated satisfaction with first-time anal cancer screening using high resolution anoscopy (HRA) as a cross ...sectional survey among men who have sex with men (MSM) attending a community-engaged clinic in Abuja, Nigeria.
Between March and August 2017, 342 MSM underwent screening and 307 (89%) completed a satisfaction survey that evaluated 8 domains related to expectations, convenience, staff interpersonal skills, physical surroundings, technical competence, pain/discomfort, general satisfaction, and intention to re-screen if symptomatic. The 22-item questionnaire used 5-point Likert scales ranging from 1 (strongly disagree) to 5 (strongly agree). For each domain, responses to specific items were averaged, aggregated, and converted to a 100-point scaled score (SS) with 25 and 75 corresponding to disagree and agree, respectively.
Median age was 24 years (interquartile range IQR: 22-28), median years since anal coital debut was 7 (IQR: 4-12), and 58% (95% confidence interval CI: 52-64%) were living with HIV. Despite respondents reporting pre-procedure anxiety (SS:73), most were comfortable with the setting and procedure and reported overall satisfaction (SS:74-76). Willingness to undergo future screening had the lowest score (SS:69) within the general satisfaction domain. The lowest scoring domains were pain/discomfort (SS:57) and agreement to re-screen if symptomatic (SS:59), which correlated with lower overall satisfaction (p < 0.001). Domain responses did not differ by HIV infection after adjusting for multiple comparisons (p > 0.006) or number of anal biopsies (all p > 0.05).
Overall, HRA was satisfactory for those naïve to screening but moving forward necessitates monitoring levels of discomfort with pain scales and normalizing dialogue around clinical symptoms of anal cancer and overall anal health to sustain future screening.
Background Routine screening for HIV and other sexually transmitted infections (STIs) facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We estimated the ...prevalence of prior HIV/STI testing among men who have sex with men (MSM) and transgender women (TGW) in Bangkok, Thailand, and identified factors associated with prior testing. Methods Cross-sectional analyses were performed using data collected at enrollment into an HIV incidence cohort. From April to October 2017, MSM and TGW were enrolled if they were aged 18-35 years, reported anal intercourse with a male or TGW partner, and reported behavioral vulnerability to HIV. Participants answered questions about demographics, sexual behaviors, and lifetime HIV/STI testing history. Multivariable robust Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for factors potentially associated with prior testing. Results Among 1,014 participants, 348 (34.3%) were TGW and the median age was 21.6 (interquartile range 20.0-24.8) years. Prior testing for HIV was reported by 421 (41.5%) and for other STIs by 268 (26.4%). HIV testing was more common among participants aged greater than or equai to 22 years (RR 1.37 95% CI 1.13-1.67), with college education as compared to secondary or less (RR 1.37 95% CI 1.08-1.72), and who met male sexual partners online (RR 1.52 95% CI 1.24-1.85), but lower among participants attracted to both men and women as compared to men only (RR 0.64 95% CI 0.51-0.81) and who met male sexual partners in bars (RR 0.83 95% CI 0.72-0.97). Similar associations were observed with prior testing for other STIs, including increased testing among participants with college education (RR 1.52 95% CI 1.11-2.09) and who met male sexual partners online (RR 1.73 95% CI 1.30-2.31), but lower among participants attracted to both men and women (RR 0.70 95% CI 0.51-0.96) and who met male sexual partners in bars (RR 0.67 95% CI 0.54-0.83). Conclusions Despite behavioral vulnerability, prior testing for HIV and other STIs was uncommon. Online engagement strategies may be effectively reaching Thai MSM and TGW who meet sexual partners online, but new interventions are needed to encourage testing among younger, less educated, and bisexual MSM and TGW. Keywords: Screening practices, Sexual and gender minorities, Human immunodeficiency virus, Testing practices, Screening practices, Voluntary counseling and testing, Early diagnosis, Healthcare acceptability
Abstract
Overcoming stigma affecting gay, bisexual, and other men who have sex with men (MSM) is a foundational element of an effective response to the human immunodeficiency virus (HIV) pandemic. ...Quantifying the impact of stigma mitigation interventions necessitates improved measurement of stigma for MSM around the world. In this study, we explored the underlying factor structure and psychometric properties of 13 sexual behavior stigma items among 10,396 MSM across 8 sub-Saharan African countries and the United States using cross-sectional data collected between 2012 and 2016. Exploratory factor analyses were used to examine the number and composition of underlying stigma factors. A 3-factor model was found to be an adequate fit in all countries (root mean square error of approximation = 0.02–0.05; comparative fit index/Tucker-Lewis index = 0.97–1.00/0.94–1.00; standardized root mean square residual = 0.04–0.08), consisting of “stigma from family and friends,” “anticipated health-care stigma,” and “general social stigma,” with internal consistency estimates across countries of α = 0.36–0.80, α = 0.72–0.93, and α = 0.51–0.79, respectively. The 3-factor model of sexual behavior stigma cut across social contexts among MSM in the 9 countries. These findings indicate commonalities in sexual behavior stigma affecting MSM across sub-Saharan Africa and the United States, which can facilitate efforts to track progress on global stigma mitigation interventions.
Malaria and schistosomiasis present considerable disease burden in tropical and sub-tropical areas and severity is worsened by co-infections in areas where both diseases are endemic. Although ...pathogenesis of these infections separately is well studied, there is limited information on the pathogenic disease mechanisms and clinical disease outcomes in co-infections. In this study, we investigated the prevalence of malaria and schistosomiasis co-infections, and the hematologic and blood chemistry abnormalities in asymptomatic adults in a rural fishing community in western Kenya. This sub-study used samples and data collected at enrollment from a prospective observational cohort study (RV393) conducted in Kisumu County, Kenya. The presence of malaria parasites was determined using microscopy and real-time-PCR, and schistosomiasis infection by urine antigen analysis (CCA). Hematological analysis and blood chemistries were performed using standard methods. Statistical analyses were performed to compare demographic and infection data distribution, and hematologic and blood chemistry parameters based on different groups of infection categories. Clinically relevant hematologic conditions were analyzed using general linear and multivariable Poisson regression models. From February 2017 to May 2018, we enrolled 671 participants. The prevalence of asymptomatic Plasmodium falciparum was 28.2% (157/556) and schistosomiasis 41.2% (229/562), with 18.0% (100/556) of participants co-infected. When we analyzed hematological parameters using Wilcoxon rank sum test to evaluate median (IQR) distribution based on malarial parasites and/or schistosomiasis infection status, there were significant differences in platelet counts (p = 0.0002), percent neutrophils, monocytes, eosinophils, and basophils (p < 0.0001 each). Amongst clinically relevant hematological abnormalities, eosinophilia was the most prevalent at 20.6% (116/562), whereas thrombocytopenia was the least prevalent at 4.3% (24/562). In univariate model, Chi-Square test performed for independence between participant distribution in different malaria parasitemia/schistosomiasis infection categories within each clinical hematological condition revealed significant differences for thrombocytopenia and eosinophilia (p = 0.006 and p < 0.0001, respectively), which was confirmed in multivariable models. Analysis of the pairwise mean differences of liver enzyme (ALT) and kidney function (Creatinine Clearance) indicated the presence of significant differences in ALT across the infection groups (parasite + /CCA + vs all other groups p < .003), but no differences in mean Creatinine Clearance across the infection groups. Our study demonstrates the high burden of asymptomatic malaria parasitemia and schistosomiasis infection in this rural population in Western Kenya. Asymptomatic infection with malaria or schistosomiasis was associated with laboratory abnormalities including neutropenia, leukopenia and thrombocytopenia. These abnormalities could be erroneously attributed to other diseases processes during evaluation of diseases processes. Therefore, evaluating for co-infections is key when assessing individuals with laboratory abnormalities. Additionally, asymptomatic infection needs to be considered in control and elimination programs given high prevalence documented here.
Plasmacytoid dendritic cells (pDCs) are robust producers of IFNα and one of the first immune cells to respond to SIV infection. To elucidate responses to early HIV-1 replication, we studied blood ...pDCs in 29 HIV-infected participants who initiated antiretroviral therapy during acute infection and underwent analytic treatment interruption (ATI). We observed an increased frequency of partially activated pDCs in the blood before detection of HIV RNA. Concurrent with peak pDC frequency, we detected a transient decline in the ability of pDCs to produce IFNα in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-κB. The levels of phosphorylated IRF7 and NF-κB inversely correlated with plasma IFNα2 levels, implying that pDCs were refractory to in vitro stimulation after IFNα production in vivo. After ATI, decreased expression of IFN genes in pDCs inversely correlated with the time to viral detection, suggesting that pDC IFN loss is part of an effective early immune response. These data from a limited cohort provide a critical first step in understanding the earliest immune response to HIV-1 and suggest that changes in blood pDC frequency and function can be used as an indicator of viral replication before detectable plasma viremia.
•A majority of participants were willing to participate in future HIV vaccine trials.•Among participants who unwilling to participate, fear of getting HIV was major driver.•More engagement in care ...may reduce hesitancy and increase participation in future trials.•Educating about ongoing vaccine research may reduce fears about participating.
Future efficacy testing of interventions to prevent HIV or other infections will require engagement of vulnerable populations. We characterized willingness to participate in a future HIV vaccine trial and barriers to participation among men who have sex with men in a 12-month German cohort study. Among 1015 participants at enrollment, 604 (60%) reported willingness, 60 (6%) were unwilling, 351 (35%) were unsure or refused to answer. Among those unwilling, the primary reason was fear of getting HIV. Among those willing, reasons included protection against HIV and furthering scientific knowledge. In a multivariable logistic regression model, higher odds of willingness to participate were seen among participants at the 12-month visit (aOR: 1.09, 95% CI: 1.04–1.15) and with prior knowledge of HIV vaccine research (aOR: 1.14, 95% CI: 1.06–1.23). Educating potential participants about vaccine research may facilitate recruitment and participation in future trials of HIV vaccine candidates and other prevention interventions.
We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a ...data-driven approach.
A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables.
Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count.
Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.
Among 413 Nigerian men who have sex with men and transgender women, retrospective testing for Mycoplasma genitalium revealed mostly asymptomatic infections of the anorectum (prevalence, 36.8%; ...incidence, 18.4 cases/100 person-years) and urogenital tract (12.4%, 4.0 cases/100 person-years). Risk factors included HIV and increasing number of sex partners.
To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.
Single-arm trial of ART initiation during AEHI ...at 30 sites in the Americas, Africa, and Asia.
HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines.
From 2017 to 2019, 188 participants initiated ART during Fiebig stages I ( n = 6), II ( n = 43), III ( n = 56), IV ( n = 23), and V ( n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels ( P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4 + or CD8 + T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest.
Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.
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