Understanding HIV Transmission Research Articles

Rectal mucosal inflammation, microbiome, and wound healing in men who have sex with men who engage in receptive anal intercourse

Abstract Mucosal injury is common during consensual intercourse and induces an inflammatory response that could contribute to pathogen transmission including HIV. Here, we compared mucosal immune and microbiome responses to experimentally induced mucosal injury between men who have sex with men engaging in receptive anal intercourse (MSM-RAI) and men who do not engage in RAI (controls), all without HIV. Rectal mucosal secretions were collected from adult MSM-RAI (n = 19) and controls (n = 6) via anoscopy before and up to eight days after experimentally induced injury. Mucosal healing was evaluated by repeated injury surface area measurements with digital imaging. MSM-RAI demonstrated overall significantly higher concentrations of pro-inflammatory cytokines and a distinct rectal microbiome compared with controls. Wound healing was numerically faster in MSM-RAI but did not meet statistical significance (p = 0.09). Different cytokine injury response patterns were observed between MSM-RAI and controls; however, IL-6 and IP-10 were important mediators in both groups. Microbial guilds, particularly from the Lachnospiraceae and Prevotellaceae families, were associated with rectal mucosal inflammation. This work is the first experimental study of rectal mucosal injury and the immune environment in healthy humans and provides a more nuanced understanding of rectal mucosal inflammation after injury, which can inform our understanding of HIV transmission.

Explainable artificial intelligence and domain adaptation for predicting HIV infection with graph neural networks

Objective Investigation of explainable deep learning methods for graph neural networks to predict HIV infections with social network information and performing domain adaptation to evaluate model transferability across different datasets. Methods Network data from two cohorts of younger sexual minority men (SMM) from two U.S. cities (Chicago, IL, and Houston, TX) were collected between 2014 and 2016. Feature importance from graph attention network (GAT) models were determined using GNNExplainer. Domain adaptation was performed to examine model transferability from one city dataset to the other dataset, training with 100% of the source dataset with 30% of the target dataset and prediction on the remaining 70% from the target dataset. Results Domain adaptation showed the ability of GAT to improve prediction over training with single city datasets. Feature importance analysis with GAT models in single city training indicated similar features across different cities, reinforcing potential application of GAT models in predicting HIV infections through domain adaptation. Conclusion GAT models can be used to address the data sparsity issue in HIV study populations. They are powerful tools for predicting individual risk of HIV that can be further explored for better understanding of HIV transmission.

Estimating HIV incidence in sub-Saharan Africa

Over the past 3 years, the COVID-19 pandemic has affected health systems in sub-Saharan Africa that were already highly burdened by other infectious diseases such as HIV.1 Although substantial progress has been made in reducing new HIV infections globally, Africa is still disproportionately affected, accounting for two-thirds of all people living with HIV.2 The global target to achieve 95% of HIV testing, treatment, and controlled viral suppression by 2030 requires nuanced and innovative ways of understanding HIV transmission dynamics at the national, regional, and subregional levels, and availability of new treatments and preventive strategies on a broad scale.

Interplay Between Geography and HIV Transmission Clusters in Los Angeles County.

BackgroundClusters of HIV diagnoses in time and space and clusters of genetically linked cases can both serve as alerts for directing prevention and treatment activities. We assessed the interplay between geography and transmission across the Los Angeles County (LAC) HIV genetic transmission network.MethodsDeidentified surveillance data reported for 8186 people with HIV residing in LAC from 2010 through 2016 were used to construct a transmission network using HIV-TRACE. We explored geographic assortativity, the tendency for people to link within the same geographic region; concordant time–space pairs, the proportion of genetically linked pairs from the same geographic region and diagnosis year; and Jaccard coefficient, the overlap between geographical and genetic clusters.ResultsGeography was assortative in the genetic transmission network but less so than either race/ethnicity or transmission risk. Only 18% of individuals were diagnosed in the same year and location as a genetically linked partner. Jaccard analysis revealed that cis-men and younger age at diagnosis had more overlap between genetic clusters and geography; the inverse association was observed for trans-women and Blacks/African Americans.ConclusionsWithin an urban setting with endemic HIV, genetic clustering may serve as a better indicator than time–space clustering to understand HIV transmission patterns and guide public health action.

Mapping of HIV-1C Transmission Networks Reveals Extensive Spread of Viral Lineages Across Villages in Botswana Treatment-as-Prevention Trial.

Phylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions. We obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013-2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood. We obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2-27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities. A large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018.

Ethical issues associated with HIV molecular epidemiology: a qualitative exploratory study using inductive analytic approaches

BackgroundHIV molecular epidemiology is increasingly recognized as a vital source of information for understanding HIV transmission dynamics. Despite extensive use of these data-intensive techniques in both research and public health settings, the ethical issues associated with this science have received minimal attention. As the discipline evolves, there is reasonable concern that existing ethical and legal frameworks and standards might lag behind the rapid methodological developments in this field. This is a follow-up on our earlier work that applied a predetermined analytical framework to examine the perspectives of a sample of scientists from the fields of epidemiology, public health, virology and bioethics on key ethical issues associated with HIV molecular epidemiology in HIV network research.MethodsFourteen in-depth interviews were conducted with scientists from the fields of molecular epidemiology, public health, virology and bioethics. Inductive analytical approaches were applied to identify key themes that emerged from the data.ResultsOur interviewees acknowledged the potential positive impact of molecular epidemiology in the fight against HIV. However, they were concerned that HIV phylogenetics research messages may be incorrectly interpreted if not presented at the appropriate level. There was consensus that HIV phylogenetics research presents a potential risk to privacy, but the probability and magnitude of this risk was less obvious. Although participants acknowledged the social value that could be realized from the analysis of HIV genetic sequences, there was a perceived fear that the boundaries for use of HIV sequence data were not clearly defined.Conclusions Our findings highlight distinct ethical issues arising from HIV molecular epidemiology. As the discipline evolves and HIV sequence data become increasingly available, it is critical to ensure that ethical standards keep pace with biomedical advancements. We argue that the ethical issues raised in this study, whether real or perceived, require further conceptual and empirical examination.

A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC.

Washington, DC consistently has one of the highest annual rates of new HIV-1 diagnoses in the United States over the last 10 years. To guide intervention and prevention strategies to combat DC HIV infection, it is helpful to understand HIV transmission dynamics in a historical context. Toward this aim, we conducted a retrospective study (years 1987–2015) of 3,349 HIV pol sequences (1,026 bp) from 1,995 individuals living in the DC area belonging to three different cohorts. We coupled HIV sequence data with clinical information (sex, risk factor, race/ethnicity, viral load, subtype, anti-retroviral regimen) to identify circulating drug resistant mutations (DRM) and transmission clusters and assess their persistence over time. Of the transmission clusters identified in the DC area, 78.0 and 31.7% involved MSM and heterosexuals, respectively. The longest spread of time for a single cluster was 5 years (2007–2012) using a distance-based network inference approach and 27 years (1987–2014) using a maximum likelihood phylogenetic approach. We found eight subtypes and nine recombinants. Genetic diversity increased steadily over time with a slight peak in 2009 and remained constant thereafter until 2015. Nucleotide diversity also increased over time while relative genetic diversity (BEAST) remained relatively steady over the last 28 years with slight increases since 2000 in subtypes B and C. Sequences from individuals on drug therapy contained the highest total number of DRMs (1,104–1,600) and unique DRMs (63–97) and the highest proportion (>20%) of resistant individuals. Heterosexuals (43.94%), MSM (40.13%), and unknown (44.26%) risk factors showed similar prevalence of DRMs, while injection drug users had a lower prevalence (33.33%). Finally, there was a 60% spike in the number of codons with DRMs between 2007 and 2010. Past patterns of HIV transmission and DRM accumulation over time described here will help to predict future efficacy of ART drugs based on DRMs persisting over time and identify risk groups of interest for prevention and intervention efforts within the DC population. Our results show how longitudinal data can help to understand the temporal dynamics of HIV-1 at the local level.

Completeness of HIV nucleotide sequence ascertainment and its potential impact on understanding HIV transmission – Maryland, 2011–2013

ABSTRACTHIV nucleotide sequences generated through routine drug resistance testing (DRT) and reported to Maryland's Molecular HIV Surveillance system are most effective for elucidating transmission patterns and identifying outbreaks if DRT is ordered promptly and sequences are reported completely. Among reported cases of HIV infection newly diagnosed during 2011–2013 in Maryland residents aged ≥13 years, we assessed sequence ascertainment completeness. To better understand which populations were most likely to have a sequence, we examined associations between sequence ascertainment and clinical and demographic characteristics. During 2011–2013, 4423 new HIV infection diagnoses were reported; sequences were ascertained for 1282 (29.0%). Among 3267 cases with complete data, odds for having a sequence ascertained were highest for cases in persons living inside Maryland's Central Region with initial CD4 counts ≤500 cells/mm3 (adjusted odds ratio [aOR] 2.4, 95% confidence interval [CI] 1.9–3.1). Sequence ascertainment did not vary significantly by patient age, sex, race/ethnicity or HIV transmission category. Educational interventions, policy changes and improved processes to increase timely DRT and subsequent sequence reporting with a focus on testing at entry to care, particularly for those with higher CD4 counts and those living outside the Central Region, might improve ascertainment completeness.

Development of a Multiplex Assay for Concurrent Diagnoses and Detection of HIV-1, HIV-2, and Recent HIV-1 Infection in a Single Test.

Laboratory assays that can accurately distinguish recent (occurring within the past year) from long-standing (>1 year) HIV infection are crucial for understanding HIV transmission dynamics in a population. However, often these efforts are confounded by inaccurate HIV diagnosis and the presence of HIV-2 in the population being surveyed. This study describes development of a multiplex assay that can simultaneously perform HIV diagnosis, HIV serotyping, and detection of recent HIV-1 infection in a single well. HIV diagnosis and HIV-2 serotyping were accomplished by coupling beads with an HIV-1 p24-gp41 fusion protein and HIV-2 peptide from gp36 immunodominant region, respectively. HIV-1 recent infection detection was accomplished by coupling beads with limiting amounts of multi-subtype gp41 immunodominant protein, recombinant immunodominant region, group M (rIDR-M). Assay conditions, including concentration of coupled antigens, were systematically optimized using well-characterized specimens with known HIV-status (positive or negative), HIV-2 specimens, and recent or long-term HIV-1 classification based on LAg-Avidity enzyme immunoassay (EIA) in a stepwise manner. Beads were then combined in a multiplex assay to evaluate its performance using large panel of specimens (n = 1,500) that included HIV-1 positive (n = 570, recent = 78, long-term = 492), HIV-2 positive (n = 31), and seronegative individuals (n = 899). The diagnostic component of the assay performed with high sensitivity (99.8%) and specificity (99.7%), while the HIV-2 serotyping sensitivity and specificity were 96.7% and 100%, respectively. There was a high correlation (R = 0.84) between the LAg-Avidity EIA and the multiplex assay for recent infection detection. The assay showed high inter- and intra-assay reproducibility with %coefficient of variation of <10% in the dynamic range. The multiplex assay has the ability to diagnose HIV infection, perform serotyping, and detect and distinguish recent from long-term HIV infections, all in a single well. This novel assay has the potential to simplify HIV surveillance by reducing the multiple steps that are otherwise required.

Social network and HIV risk behaviors in female sex workers: a systematic review

BackgroundSocial network characteristics have an important role in understanding HIV transmission among female sex workers. The purpose of this systematic review was to summarize and critically appraise the existing studies on the social network characteristics and HIV risk behaviors among female sex workers.MethodA systematic review was performed using predefined eligibility criteria through searching electronic databases. Two independent reviewers assessed the methodological quality of studies.ResultsNineteen papers met the eligible review criteria. The synthesized evidence suggests that characteristics of social networks, especially functional characteristics such as social support and social capital, are important constructs for understanding the HIV risk behaviors.ConclusionsThe findings of the present review enhance our understanding of the role of social network characteristics in HIV risk behaviors among female sex workers. However, the findings also highlighted a dearth of knowledge about the association of structural characteristics of social networks with HIV risk behaviors among female sex workers.

Leveraging Phylogenetics to Understand HIV Transmission and Partner Notification Networks

Partner notification is an important component of public health test and treat interventions. To enhance this essential function, we assessed the potential for molecular methods to supplement routine partner notification and corroborate HIV networks. All persons diagnosed with HIV infection in Wake County, NC, during 2012-2013 and their disclosed sexual partners were included in a sexual network. A data set containing HIV-1 pol sequences collected in NC during 1997-2014 from 15,246 persons was matched to HIV-positive persons in the network and used to identify putative transmission clusters. Both networks were compared. The partner notification network comprised 280 index cases and 383 sexual partners and high-risk social contacts (n = 131 HIV-positive). Of the 411 HIV-positive persons in the partner notification network, 181 (44%) did not match to a HIV sequence, 61 (15%) had sequences but were not identified in a transmission cluster, and 169 (41%) were identified in a transmission cluster. More than half (59%) of transmission clusters bridged sexual network partnerships that were not recognized in the partner notification; most of these clusters were dominated by men who have sex with men. Partner notification and HIV sequence analysis provide complementary representations of the existent partnerships underlying the HIV transmission network. The partner notification network components were bridged by transmission clusters, particularly among components dominated by men who have sex with men. Supplementing the partner notification network with phylogenetic data highlighted avenues for intervention.

Network Research Experiences in New York and Eastern Europe: Lessons for the Southern US in Understanding HIV Transmission Dynamics.

This paper presents an overview of different kinds of risk and social network methods and the kinds of research questions each can address. It also reviews what network research has discovered about how network characteristics are associated with HIV and other infections, risk behaviors, preventive behaviors, and care, and discusses some ways in which network-based public health interventions have been conducted. Based on this, risk and social network research and interventions seem both feasible and valuable for addressing the many public health and social problems raised by the widespread use of opioids in the US South.

Leveraging phylogenetics to understand HIV transmission and partner notification networks

Leveraging phylogenetics to understand HIV transmission and partner notification networks

HIV Transmission Dynamics Among Foreign-Born Persons in the United States.

In the United States (US), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from US-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV. Using HIV-1 polymerase nucleotide sequences reported to the US National HIV Surveillance System for persons with diagnosed HIV infection during 2001-2013, we constructed a genetic distance-based transmission network using HIV-TRACE and examined the birth region of potential transmission partners in this network. Of 77,686 people, 12,064 (16%) were foreign born. Overall, 28% of foreign-born persons linked to at least one other person in the transmission network. Of potential transmission partners, 62% were born in the United States, 31% were born in the same region as the foreign-born person, and 7% were born in another region of the world. Most transmission partners of male foreign-born persons (63%) were born in the United States, whereas most transmission partners of female foreign-borns (57%) were born in their same world region. These finding suggests that a majority of HIV infections among foreign-born persons in our network occurred after immigrating to the United States. Efforts to prevent HIV infection among foreign-born persons in the United States should include information of the transmission networks in which these individuals acquire or transmit HIV to develop more targeted HIV prevention interventions.

Status is not everything

HIV Many parameters are examined to try to understand HIV transmission in endemic areas. Tanser et al. used longitudinal data from rural South Africa to argue that a “population viral load” index incorporating geographical location and local prevalence is important to infer transmission. Accounting for HIV-negative individuals in calculations and transmission models is important for appropriate interpretations. Such analyses could be helpful in guiding treatment intervention in these regions. Sci. Transl. Med. 9 , eaam8012 (2017).

Understanding HIV Transmission and Illness Stigma: A Relationship Revisited in Rural Rwanda.

Integrating an understanding of HIV transmission with structural-behavioral prevention approaches remains a priority in low prevalence rural regions in Africa. Many national indicators use categorical survey responses which do not capture the cultural nuances of HIV transmission knowledge that potentially reify stigmatizing treatment of persons living with HIV (PL-HIV). We examined the relationship between quantitative and qualitative measures of HIV knowledge and four forms of stigma (individual attitudes, felt normative, social distance, and stigma perceived by PLHIV) among 200 rural residents in Rwanda. Forty-two percent qualitatively reported concurrent accurate and partial knowledge of HIV transmission. Being more knowledgeable about HIV transmission was associated with less desire for social distancing from PLHIV. Our findings highlight the continued importance of reinforcing an accurate understanding of HIV transmission and correcting misinformation by drawing on quantitative and qualitative assessments of HIV knowledge as critical arms of HIV stigma reduction programs in low prevalence rural regions.

Anal sexual experience and HIV risk awareness among female sex workers in Dire Dawa, eastern Ethiopia

BackgroundFemale sex workers have been disproportionately affected with HIV and anal sexual experience elevate their vulnerability. Anal intercourse has more risk of HIV transmission than vaginal intercourse for receptors that coupled with low condom and proper lubricant use behavior during anal sex. Besides majority of them did not understand HIV transmission risk of anal intercourse. In Ethiopia, studies on anal sexual experience is almost none existent, so the purpose of this study is to explored anal sexual experience and HIV transmission risk awareness among female sex worker in Dire Dawa, Eastern Ethiopia.MethodQualitative study with thematic analysis approach was conducted among 18 female sex workers and recruitment of study participants performed until saturation of information. The principal investigator conducted in-depth interviews using local language (Amharic) and it was recorded on audio recorder. Tape recorded data was transcribed and translated to English and entered into open code version 3.4 for coding and theme identification. Data collection conducted simultaneously with data analysis.ResultFemale sex workers practiced anal sex for different themes like financial influence, coercion, intentionally, peer pressure and as a sign of intimacy and love. Coercion, negative attitudes, poor awareness about HIV transmission risks of anal sex and protection capacity of condom and proper lubricants are the identified themes for not using condom and proper lubricants during anal sex by female sex workers. Inaccessibility and unavailability of health services for issues related to anal sex was the core reason for female sex workers’ misperception and risk anal sexual experience.ConclusionFemale sex workers practiced anal sex without risk reduction approaches and they did not understand exacerbated risk of anal sex to HIV transmission. Stakeholders including ministry of health need to incorporate potential awareness raising tasks and programs about risk of anal sex and methods of risk reduction for female sex workers.

Genetic transmission networks reveal the transmission patterns of HIV-1 CRF01_AE in China

ObjectivesThe epidemic of HIV-1 CRF01_AE has become a major public health issue in China. This study aimed to characterise the transmission patterns of genetic networks for CRF01_AE nationwide and elucidate...

Genetic Transmission Networks Reveal the Transmission Patterns of HIV-1 CRF01_AE in China

Abstract The epidemic of HIV-1 CRF01_AE has become one of major public health issues in China. We sought to characterize the transmission patterns of networks for this strain nationwide and elucidate possible opportunities for prevention. All available CRF01_AE pol sequences (n = 4, 704) from China in the HIV LANL were isolated and conducted genetic transmission network analysis. A total of 1, 391 (29.6%) sequences were identified as belonging to 400 separate networks. Of men who have sex with men (MSM) in networks, 93.8% were linked to other MSM and only 2.4% were linked to heterosexual women. However, 11.8% heterosexual women in networks were linked to MSM. The lineages mainly composed of MSM had a higher transmission than those major consisted of heterosexuals. Of the 1, 391 individuals in networks, 36.9% (513) were linked to cases diagnosed in different provinces. The proportions of individuals involved in inter-province links by province was interrelated with the number of migrant people (Spearman r =0.738, P =0.001). This study could help improve our ability to understand HIV transmission among various regions and risk groups in China, and highlighted the importance of targeting MSM and migrants by prevention and intervention efforts.

HIV Prevalence and Demographic Determinants of Unprotected Anal Sex and HIV Testing among Male Refugees Who have Sex with Men in Beirut, Lebanon.

Men who have sex with men (MSM), the same as refugees are at higher risk for health issues including HIV infection. With the large influx of refugees to Lebanon, and to better understand HIV transmission in this setting, we explored the socio-demographic correlates of condom use and HIV testing among MSM refugees in Beirut, by surveying and testing 150 participants. 67% self-identified as gay, 84.6% of respondents reported unprotected anal intercourse (UAI) in the prior 3months, and 56.7% with men of positive or unknown HIV status (UAIPU). 2.7% tested positive for HIV, and 36% reported having engaged in sex work. Men in a relationship and men who self-identified as gay had higher odds of UAI, of ever been tested, but lower odds of UAIPU. HIV prevention and testing promotion efforts targeting MSM refugees need to account for how men self-identify in relation to their sexual behavior and relationship status. Such efforts also should place emphasis on MSM of lower socio-economic status.