INTRODUCTION:COVID-19 vaccination significantly reduces COVID-19-related hospitalization and mortality and is important for those who may be at increased risk of SARS-CoV-2 infection, including people living with HIV. Using a population-based approach, we examined COVID-19 vaccine uptake among people living with and without HIV in Ontario, Canada. METHODS:A retrospective population-based matched cohort study was conducted using provincial clinical and health administrative data from December 14, 2020 to August 31, 2022. Community-dwelling adults living with HIV aged ≥19 years were matched one-to-one with a person without a diagnosis of HIV based on age, sex, geography, and immigration status. To identify predictors of vaccine uptake, modified Poisson regression with robust standard errors accounting for geographical clustering was used. To estimate vaccine uptake comparing the HIV and non-HIV cohorts, conditional Poisson regression with robust error variance was used to estimate crude and adjusted risk ratios with 95 % confidence intervals (CI). RESULTS:Among 20,903 people living with HIV, most (85.4%) had received ≥2 COVID-19 vaccine doses, with 64.7% receiving a third dose and 24.3% receiving a fourth dose. Disparities in uptake of ≥3 doses by sex were observed (males vs females: 68.5% vs 50.9%). Predictors of receiving ≥3 doses among people living with HIV included older age, male sex, and receipt of a recent influenza vaccine. Men living with HIV were more likely to receive ≥3 doses compared with men living without HIV, whereas women living with HIV were less likely than women living without HIV to receive ≥3 doses. CONCLUSIONS:Uptake of the first two doses of COVID-19 vaccine was high among people living with HIV in Ontario, Canada, however, disparities in uptake of ≥3 doses remain, especially by sex. Continued monitoring of COVID-19 vaccine uptake is crucial to informing immunization programs, policies and guidelines for people living with HIV in Canada.

We found that risk of SARS-CoV-2 breakthrough infection did not meaningfully differ between a population-based cohort of vaccinated people with HIV and a matched cohort of people without HIV after accounting for sociodemographic factors, previous SARS-CoV-2 infection, SARS-CoV-2 testing patterns and COVID-19 vaccine doses (14 December 2020 to 5 May 2024). However, rates of breakthrough infection were higher among men with HIV compared to without HIV during the pre-Omicron era.

We found that rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and reverse transcriptase (RT)-PCR-confirmed infection were approximately 50% higher in a population-based cohort of people with HIV compared with a matched cohort of people without HIV during the Omicron era (2 January 2022 to 31 March 2023) in Ontario, Canada, after controlling for age, sex, residential census tract, and country of birth. Rates of coronavirus disease 2019 (COVID-19)-related hospitalization and/or death were more than double. Differences persisted independent of vaccination, healthcare access, and COVID-19 diagnosis.

The original ‘BETTER’ (Building on Existing Tools To Improve Chronic Disease Prevention and Screening in Primary Care) approach consisted of a prevention-focused visit between participants aged 40–65 years and a “Prevention Practitioner” (PP), who empowered the participant to set achievable prevention and screening goals for cancers and chronic diseases. BETTER was successfully adapted for economically deprived communities (BETTER HEALTH) in Canada. Our objective was to conduct a review of guidelines in preparation for adapting the ‘BETTER HEALTH’ approach for younger adults aged 18–39 years living with lower income, a group known to have earlier mortality due to a higher prevalence of preventable chronic diseases than their peers with higher income. We searched multiple electronic databases and grey literature for clinical practice guidelines on prevention/screening and included those that met the following criteria: published in English from 2008–2020 in Canada or any of the following countries (Australia, Ireland, New Zealand, Scotland, United States and England); and addressed prevention or screening. We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and extracted data (publication details, recommendations, and Quality/Level of evidence as reported by authors) from sources with overall scores of 5 or higher. Final recommendations were compiled after harmonization with input from diverse stakeholders (co-investigators, PPs, and the Community Advisory Committee). We included a total of 85 guidelines, and developed a final list of 42 recommendations for 18–39 year-olds across 21 topics. Specific recommendations fell under the following topics: cancers, cardiovascular disease, diabetes, obesity, lifestyle (alcohol; healthy nutrition/physical activity); healthy relationships and healthy sexuality, immunization, oral health, social determinants of health, and substance use. We identified evidence-based guidelines on individual-level prevention/screening actions for adults 18–39 years old and relevant for those living with lower income which will directly inform development and implementation of the BETTER LIFE intervention.

ObjectivesTo identify COVID-19 infectious disease models that accounted for social determinants of health (SDH).MethodsWe searched MEDLINE, EMBASE, Cochrane Library, medRxiv, and the Web of Science from December 2019 to August 2020. We included mathematical modelling studies focused on humans investigating COVID-19 impact and including at least one SDH. We abstracted study characteristics (e.g., country, model type, social determinants of health) and appraised study quality using best practices guidelines.Results83 studies were included. Most pertained to multiple countries (n = 15), the United States (n = 12), or China (n = 7). Most models were compartmental (n = 45) and agent-based (n = 7). Age was the most incorporated SDH (n = 74), followed by gender (n = 15), race/ethnicity (n = 7) and remote/rural location (n = 6). Most models reflected the dynamic nature of infectious disease spread (n = 51, 61%) but few reported on internal (n = 10, 12%) or external (n = 31, 37%) model validation.ConclusionFew models published early in the pandemic accounted for SDH other than age. Neglect of SDH in mathematical models of disease spread may result in foregone opportunities to understand differential impacts of the pandemic and to assess targeted interventions.Systematic Review Registration:[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020207706], PROSPERO, CRD42020207706.

BACKGROUND:Infectious disease (ID) models have been the backbone of policy decisions during the COVID-19 pandemic. However, models often overlook variation in disease risk, health burden, and policy impact across social groups. Nonetheless, social determinants are becoming increasingly recognized as fundamental to the success of control strategies overall and to the mitigation of disparities. METHODS:To underscore the importance of considering social heterogeneity in epidemiological modeling, we systematically reviewed ID modeling guidelines to identify reasons and recommendations for incorporating social determinants of health into models in relation to the conceptualization, implementation, and interpretations of models. RESULTS:After identifying 1,372 citations, we found 19 guidelines, of which 14 directly referenced at least 1 social determinant. Age (n = 11), sex and gender (n = 5), and socioeconomic status (n = 5) were the most commonly discussed social determinants. Specific recommendations were identified to consider social determinants to 1) improve the predictive accuracy of models, 2) understand heterogeneity of disease burden and policy impact, 3) contextualize decision making, 4) address inequalities, and 5) assess implementation challenges. CONCLUSION:This study can support modelers and policy makers in taking into account social heterogeneity, to consider the distributional impact of infectious disease outbreaks across social groups as well as to tailor approaches to improve equitable access to prevention, diagnostics, and therapeutics. HIGHLIGHTS:Infectious disease (ID) models often overlook the role of social determinants of health (SDH) in understanding variation in disease risk, health burden, and policy impact across social groups.In this study, we systematically review ID guidelines and identify key areas to consider SDH in relation to the conceptualization, implementation, and interpretations of models.We identify specific recommendations to consider SDH to improve model accuracy, understand heterogeneity, estimate policy impact, address inequalities, and assess implementation challenges.

Abstract Background The original ‘BETTER’ (Building on Existing Tools To Improve Chronic Disease Prevention and Screening in Primary Care) approach consisted of a prevention-focused visit between participants aged 40–65 years and a “Prevention Practitioner” (PP), who empowered the participant to set achievable prevention and screening goals for cancers and chronic diseases. BETTER was successfully adapted for economically deprived communities (BETTER HEALTH). We conducted an evidence review of guidelines in preparation for adapting the ‘BETTER HEALTH’ approach for younger adults aged 18–39 years living with lower income, a group known to have earlier mortality due to a higher prevalence of preventable chronic diseases than their peers with higher income. Methods We searched multiple electronic databases and grey literature for clinical practice guidelines on prevention/screening and included those that met the following criteria: published in English from 2008–2020 in Canada or any of the following countries (Australia, Ireland, New Zealand, Scotland, United States and England); and addressed prevention or screening. We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and extracted data from sources with overall scores of 5 or higher. Final recommendations were compiled after harmonization with input from diverse stakeholders (co-investigators, PPs, and the Community Advisory Committee). Results We included a total of 85 guidelines, and developed a final list of 42 recommendations for 18–39 year-olds across 21 topics. Specific recommendations fell under the following topics: cancers, cardiovascular disease, diabetes, obesity, lifestyle (alcohol; healthy nutrition/physical activity); healthy relationships and healthy sexuality, immunization, oral health, social determinants of health, and substance use. Conclusion We identified evidence-based guidelines on prevention/screening actions for adults 18–39 years old and relevant for those living with lower income.

Objectives: HIV pre-exposure prophylaxis (PrEP) may change serosorting patterns. We examined the influence of serosorting on the population-level HIV transmission impact of PrEP, and how impact could change if PrEP users stopped serosorting. Design: We developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among MSM in Canada. Methods: We separately fit the model with serosorting and without serosorting [counterfactual; sero-proportionate mixing (random partner-selection proportional to availability by HIV status)], and reproduced stable HIV epidemics with HIV-prevalence 10.3-24.8%, undiagnosed fraction 4.9-15.8% and treatment coverage 82.5-88.4%. We simulated PrEP-intervention reaching stable pre-specified coverage by year-one and compared absolute difference in relative HIV-incidence reduction 10 years post-intervention (PrEP-impact) between models with serosorting vs. sero-proportionate mixing; and counterfactual scenarios when PrEP users immediately stopped vs. continued serosorting. We examined sensitivity of results to PrEP-effectiveness (44-99%; reflecting varying dosing or adherence levels) and coverage (10-50%). Results: Models with serosorting predicted a larger PrEP-impact than models with sero-proportionate mixing under all PrEP-effectiveness and coverage assumptions [median (interquartile range): 8.1% (5.5-11.6%)]. PrEP users' stopping serosorting reduced PrEP-impact compared with when PrEP users continued serosorting: reductions in PrEP-impact were minimal [2.1% (1.4-3.4%)] under high PrEP-effectiveness (86-99%); however, could be considerable [10.9% (8.2-14.1%)] under low PrEP effectiveness (44%) and high coverage (30-50%). Conclusion: Models assuming sero-proportionate mixing may underestimate population-level HIV-incidence reductions due to PrEP. PrEP-mediated changes in serosorting could lead to programmatically important reductions in PrEP-impact under low PrEP-effectiveness. Our findings suggest the need to monitor sexual mixing patterns to inform PrEP implementation and evaluation.

Abstract Background HIV‐positive individuals may acquire HCV via injection drug use (IDU) and condomless anal sex. HIV care provides opportunities for HCV testing and cure with direct‐acting antiviral agents (DAAs). Methods We analyzed data from the Ontario HIV Treatment Network Cohort Study. Among those not HCV‐positive or diagnosed previously (n = 4586), we used Cox regression to test the rates of ever HCV testing (serological or RNA) in HIV care by DAA era (pre‐DAA: 2000‐2010; after DAA: 2011‐2015) and compared the proportion diagnosed with HCV. We identified correlates of annual proportions of serological testing using Poisson generalized estimating equations. Results After DAA vs pre‐DAA, the hazard rate ratio (95% CI) of ever HCV testing was 1.70 (1.59, 1.81). The proportion (95% CI) tested annually increased from 9.2% (8.0%, 10.7%) in 2000 to 39.1% (37.1%, 41.1%) in 2015 (P < 0.0001). The proportion diagnosed with HCV declined by 74% pre‐DAA to 11% after DAAs. Annual testing increased per calendar year (16% steeper slope after DAA vs pre‐DAA) and was more common among men who have sex with men; those more educated (post‐secondary vs ≤ high school); and those positive for syphilis or reporting any IDU. Annual testing decreased per decade of age and time since HIV diagnosis. Discussion Annual HCV testing increased over time with higher testing among those reporting sexual or IDU risk factors, but fell short of clinical guidelines. Targeted interventions to boost testing may be needed to close these gaps and reach WHO 2030 HCV elimination targets.

Using cross-sectional survey data (Engage, 2017-2018) from 1,137 men who have sex with men, ≥16 years old, in Montreal, we compared observed human immunodeficiency virus (HIV) seroconcordance in previous-6-months' sexual partnerships with what would have been observed by chance if zero individuals serosorted. Of 5 recent partnerships where both individuals were HIV-negative, we compared observed concordance in preexposure prophylaxis (PrEP) use with the counterfactual if zero individuals selected partners based on PrEP use. We estimated the concordance by chance using a balancing-partnerships approach assuming proportionate mixing. HIV-positive respondents had a higher proportion of HIV-positive partners (66.4%, 95% confidence interval (CI): 64.0, 68.6) than by chance (23.9%, 95% CI: 23.1, 24.7). HIV-negative respondents (both on and not on PrEP) had higher proportions of HIV-negative partners (82.9% (95% CI: 81.1, 84.7) and 90.7% (95% CI: 89.6, 91.7), respectively) compared with by chance (76.1%, 95% CI: 75.3, 76.9); however, those on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (17.1% (95% CI: 15.3, 18.9) vs. 9.3% (95% CI: 8.3, 10.4). Those on PrEP also had a higher proportion of partners on PrEP among their HIV-negative partners (50.6%, 95% CI: 42.5, 58.8) than by chance (28.5%, 95% CI: 27.5, 29.4). The relationship between PrEP and sexual-mixing patterns demonstrated by less population-level serosorting among those on PrEP and PrEP-matching warrants consideration during PrEP roll-out.

Background Existing measures of preferential partner selection do not account for attribute-concordance by chance. We quantified network-level sexual mixing by HIV status and PrEP use using a balancing partnership approach. Methods Data were from Engage, a cross-sectional survey of MSM ≥16 year-old in three Canadian cities (2017–2018). MSM with ≥1 anal/oral sex partners in the past six months (P6M) reported their own and partners’ HIV status and PrEP use. After stratifying by respondents’ HIV status (positive/negative/unknown) and P6M PrEP use (yes/no), we compared observed seroconcordance to that expected by chance among P6M-partnerships with known-status. Within HIV negative-concordant recent partnerships, we compared observed concordance in PrEP use at last sex to chance. Concordance by chance is calculated under proportionate-mixing assumption, which means the distribution of partnerships by partners’ attributes equals that by respondents’ attributes as a result of partnership balancing. We used chi-squared tests for all comparisons. Results Of the 22,102 P6M-partnerships reported by 1881 respondents (17.0%, 74.5% and 8.5% HIV-positive, negative and unknown, respectively), 60.2% comprised partners’ of known-status. 64.3% of HIV-positive respondents’ partnerships were HIV-positive (vs chance 24.6%, p<0.001). HIV-negative or status-unknown respondents had higher proportions of HIV-negative partners (87.0% and 87.5%, respectively, vs chance 75.4%, p<0.001). HIV-negative respondents on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (20.6% vs 8.4%; p<0.001). HIV-negative respondents on PrEP had a higher proportion of HIV-negative partners on PrEP (55.8% vs 34.7%); those not on PrEP had a higher proportion of HIV-negative partners not on PrEP (78.6% vs 65.3%), than chance (p<0.001). Conclusion Network-level serosorting and PrEP matching were evident after accounting for distribution of partnerships by chance. PrEP-mediated changes to mixing, such as less serosorting among MSM on PrEP, may indirectly influence the population-level HIV prevention impact of PrEP and should be included in the monitoring and evaluation of PrEP roll-out. Disclosure No significant relationships.

Background: Sexual mixing patterns influence HIV transmission dynamics. We quantified the population-level sexual mixing by two attributes (HIV status and pre-exposure prophylaxis (PrEP) use). Methods: We used data from Engage-Montreal (2017-2018), a cross-sectional survey of men who have sex with men (MSM) ≥16 year-old recruited using respondent-driven sampling. MSM with ≥1 anal/oral sex partners in the past 6 months (P6M) reported their own and partners' HIV status and PrEP use. Within P6M-partnerships across all MSM, we compared observed seroconcordance to what would have been expected by chance under proportionate mixing-if zero individual serosort. Within recent partnerships where both individuals were HIV-negative, we compared observed concordance in PrEP use at last sex to that expected by chance. We used chi-squared tests for comparisons, and calculated the excess fraction of concordance beyond chance. Findings: Of the 11,883 P6M-partnerships by 1137 respondents, 56.3% comprised partners' of known-status. Compared with by chance and among partners of known-status, HIV-positive respondents (n=207) had a higher proportion of HIV-positive partners (66.4% vs. 23.9%; p<0.001); both HIV-negative (n=831) and respondents of unknown-status (n=99) had higher proportions of HIV-negative partners (87.9%, and 92.7%, respectively, vs. 76.1%; p<0.001). HIV-negative respondents on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (17.1% vs. 9.3%; p<0.001). They also had a higher proportion of partners on PrEP among their HIV-negative partners compared with by chance (50.6% vs. 28.5%; p<0.001). Excess fractions of seroconcordance beyond chance were 64.0%, 8.9%, and 10.7% for HIV-positive, HIV-negative on PrEP, and HIV-negative not on PrEP MSM, respectively. The excess fraction of concordance in PrEP use beyond chance was 43.7%. Interpretation: The high degree of population-level serosorting and PrEP matching, and the influence of PrEP on sexual mixing patterns should be considered in the implementation of PrEP within the context of combination HIV prevention. Funding: Canadian Institutes of Health Research [TE2-138299, CTN-300, FN-13455]; Canadian Foundation for AIDS Research [Engage]; Canadian Blood Services [MSM2017LPOD]; Ontario HIV Treatment Network [1051]; Ryerson University; and Public Health Agency of Canada [4500370314]. Declaration of Interest: No conflict of interest to declare. Ethical Approval: The following institutional ethics review boards approved the study: Ryerson University, St. Michael’s Hospital, University of Toronto, University of Windsor, University of British Columbia, University of Victoria, the Simon Fraser University, and the Research Institute of the McGill University Health Centre.

Pre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes.

Background Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis. Methods A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL) rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up) and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only) to Model 2 (Model 1 plus selected markers) for predicting 3-year risk of liver fibrosis using weighted Harrell’s C and Net Reclassification Improvement indices. Results 113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60). Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype) was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI) for model 1 vs. model 2 were 0.720 (0.649, 0.791) and 0.756 (0.688, 0.825), respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p<0.05). Conclusions Including IFNL genotype and inflammatory markers IL-8, sICAM-1, RANTES, hs-CRP, and sCD14 enabled better prediction of the 3-year risk of significant liver fibrosis over clinical predictors alone. Whether this modest improvement in prediction justifies their additional cost requires further cost-benefit analyses.

Background. Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon λ3 (IFN-λ3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-λ genotypes and significant liver fibrosis in HIV-HCV coinfection. Methods. From the prospective Canadian Co-infection Cohort (n = 1423), HCV RNA–positive participants in whom IFN-λ genotypes were detected and who were free of fibrosis, end-stage liver disease, and chronic hepatitis B at baseline (n = 485) were included. Time to significant fibrosis (defined as an aspartate transaminase level to platelet count ratio index [APRI] of ≥1.5) by IFN-λ genotypes was analyzed using Cox proportional hazards, with adjustment for age, sex, ethnicity, alcohol use, CD4+ T-cell count, HCV genotype, γ-glutamyl transferase level, and baseline APRI. Haplotype analysis was performed, with adjustment for ethnicity. Results. A total of 125 participants developed fibrosis over 1595 person-years (7.84 cases/100 person-years; 95% confidence interval [CI], 6.58–9.34 cases/100 person-years). Each genotype was associated with an increased fibrosis risk, with adjusted hazard ratios of 1.37 (95% CI, .94–2.02) for rs12979860CC, 1.34 (95% CI, .91–1.97) for rs8103142TT, and 1.79 (95% CI, 1.24–2.57) for rs8099917TT. Haplotype TCT was also linked with a higher risk (hazard ratio, 1.14 [95% CI, .73–1.77]). Conclusions. IFN-λ SNPs rs12979860, rs8099917, and rs81013142 were individually linked to higher rates of fibrosis in individuals with HIV-HCV coinfection. IFN-λ genotypes may be useful to target HCV treatments to people who are at higher risk of liver disease.

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals.

Background: Dual infection with diverse HIV strains can foster the emergence of recombinants. The resulting increase in viral genetic diversity is a major challenge for vaccine development HIV treatment. In this study we aim to investigate the socio demographic factors associated with an increasing level of genetic diversity among HIV strains in a population of drug-users in Northern Thailand.Methods: From 1999 through 2000,2231 volunteers were enrolled in the Opiate-Users Research in Chiang Mai, Thailand. HIV subtype analysis was conducted among those HIV-1 seropositive (n = 347) using a multi-region hybridization assay. Social and demographic variables were assessed using a structured questionnaire.Results: Overall, 336/347 (96.8%) of the samples could be typed. 81.8% were CRF01_AE, 3.9% were subtype B, 9.2% were recombinants (mostly between CRF01_AE and B) and 5.1% were dual infections. Dual infections were more frequent among those with a lower education level (AOR: 5.2; 95% Cl 1.4-20.3), those who have initiated injecting in the last 3 years (AOR: 3.9; 95% Cl 1.1-14.6), and those reporting frequent needle sharing in the last 3 months (AOR: 7.0; 95% Cl 1.5-34.1). Both recombinant strains and dual infection were more frequent among those reporting frequent needle sharing in the last 3 months (AOR: 5.3; 95% CI 1.6-17.1).Conclusion: To limit the expanding complexity of HIV-1 strains, early intervention should be aimed at reduction in needle sharing, especially among new intravenous drug users. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Background: Non-neutralizing Abs (NNAbs) can combat viral infections by mediating immune complex clearance and Ab-dependent cell cytotoxicity (ADCC) by interacting with FcGamma receptors (FcGRs). In some cases, though, NNAbs can enhance viral infection. Genetic variants of FcGRIIa and FcGRIIIa are important due to their different binding preference and affinity for IgG subclasses, and were shown to influence levels of NNAbs elicited in a vaccine trial with rgp120 (Forthal, 2007). Few reports, and mostly from Caucasian and Asian populations, showed that polymorphic FcGRs exhibit different frequencies in diverse ethnicities. Due to the potential influence of FcGR variants for vaccines, the aim of this study was to define their distribution in East Africa, where HIV vaccine trials are underway or planned. Methods: 174 HIV seronegative consented adults from a cohort development study conducted in Mbeya, Tanzania, were studied. After DNA extraction from PBMCs, polymorphisms at FcGRIIa (131H/R) and FcGRIIIa (158V/F), were typed using real-time PCR (ABI, and newly-developed test). Genetic analyses were conducted using Pypop and Arlequin software packages. Results: Allele frequencies of variants FcGRIIa131H and FcGRIIIa158V were 0.475 and 0.326, respectively. Homozygosity for high-affinity alleles, genotypes putatively associated with enhancement of HIV infection, was frequent (131HH = 25.8%; 158VV = 12.3%; and 131HH:158VV = 4.4%). Individuals homozygous for low-affinity variants, genotypes previously associated with higher benefit from ADCC, were abundant (131RR = 30.8%; 158FF = 47.1%; and 131RR:158FF = 16.4%). Both loci were in Hardy-Weinberg equilibrium and appeared to segregate independently. Conclusion: This is an initial description of the distribution of variants of FcGRIIa and FcGRIIIa in East Africa. The high representation of genotypes having the potential for beneficial, and for detrimental effects on vaccination, makes this a preferred setting to define the impact of variation of FcGRs on vaccine efficacy, and the levels, breath and IgG subclass of neutralizing Abs and NNAbs elicited by vaccination.