HIV Transmission Dynamics Research Articles

Incorporating metadata in HIV transmission network reconstruction: A machine learning feasibility assessment.

HIV molecular epidemiology estimates the transmission patterns from clustering genetically similar viruses. The process involves connecting genetically similar genotyped viral sequences in the network implying epidemiological transmissions. This technique relies on genotype data which is collected only from HIV diagnosed and in-care populations and leaves many persons with HIV (PWH) who have no access to consistent care out of the tracking process. We use machine learning algorithms to learn the non-linear correlation patterns between patient metadata and transmissions between HIV-positive cases. This enables us to expand the transmission network reconstruction beyond the molecular network. We employed multiple commonly used supervised classification algorithms to analyze the San Diego Primary Infection Resource Consortium (PIRC) cohort dataset, consisting of genotypes and nearly 80 additional non-genetic features. First, we trained classification models to determine genetically unrelated individuals from related ones. Our results show that random forest and decision tree achieved over 80% in accuracy, precision, recall, and F1-score by only using a subset of meta-features including age, birth sex, sexual orientation, race, transmission category, estimated date of infection, and first viral load date besides genetic data. Additionally, both algorithms achieved approximately 80% sensitivity and specificity. The Area Under Curve (AUC) is reported 97% and 94% for random forest and decision tree classifiers respectively. Next, we extended the models to identify clusters of similar viral sequences. Support vector machine demonstrated one order of magnitude improvement in accuracy of assigning the sequences to the correct cluster compared to dummy uniform random classifier. These results confirm that metadata carries important information about the dynamics of HIV transmission as embedded in transmission clusters. Hence, novel computational approaches are needed to apply the non-trivial knowledge collected from inter-individual genetic information to metadata from PWH in order to expand the estimated transmissions. We note that feature extraction alone will not be effective in identifying patterns of transmission and will result in random clustering of the data, but its utilization in conjunction with genetic data and the right algorithm can contribute to the expansion of the reconstructed network beyond individuals with genetic data.

Regional disparity of HIV incidence and prevalence among men who have sex with men

BackgroundHIV incidence can be estimated with cross-sectional studies using clinical, serological, and molecular data. Worldwide, HIV incidence data in only men who have sex with men (MSM) are scarce and principally focus on those with healthcare or under treatment. However, better estimates can be obtained through studies with national representativeness. The objective was to estimate the prevalence, incidence, and factors associated with acquiring HIV in a national sample of MSM who attend meeting places, considering geographical regions.MethodsA nationally representative survey of MSM attending meeting places was performed in Mexico. Participants answered a questionnaire, and a dried blood spot (DBS) was collected. Samples were classified as recent infections using an algorithm with HIV status, antiretroviral therapy, and the result of BED-EIA assay. Parameters were analysed considering regions and demographic and sexual behaviour characteristics.ResultsThe national HIV prevalence was 17.4% with regional differences; the highest prevalence (20.7%) was found in Mexico City, and the lowest prevalence was found in the West region (11.5%). The incidence was 9.4 per 100 p/y, with regional values from 6.2 to 13.2 for the Northeast and the Centre regions, respectively. Age, age at sexual debut, low wealth index, and rewarded sex were associated with HIV prevalence. Centre region, use of private clinics as health services, and having sex exclusively with men were associated with recent HIV infections.ConclusionsThe incidence and prevalence showed regional differences, suggesting a difference in the dynamics of HIV transmission; some regions have a greater case accumulation, and others have a greater rate of new infections. Understanding this dynamic will allow developing health programs focused on HIV prevention or treating people already living with HIV.

The Role of Phylogenetics in Unravelling Patterns of HIV Transmission towards Epidemic Control: The Quebec Experience (2002-2020).

Phylogenetics has been advanced as a structural framework to infer evolving trends in the regional spread of HIV-1 and guide public health interventions. In Quebec, molecular network analyses tracked HIV transmission dynamics from 2002–2020 using MEGA10-Neighbour-joining, HIV-TRACE, and MicrobeTrace methodologies. Phylogenetics revealed three patterns of viral spread among Men having Sex with Men (MSM, n = 5024) and heterosexuals (HET, n = 1345) harbouring subtype B epidemics as well as B and non-B subtype epidemics (n = 1848) introduced through migration. Notably, half of new subtype B infections amongst MSM and HET segregating as solitary transmissions or small cluster networks (2–5 members) declined by 70% from 2006–2020, concomitant to advances in treatment-as-prevention. Nonetheless, subtype B epidemic control amongst MSM was thwarted by the ongoing genesis and expansion of super-spreader large cluster variants leading to micro-epidemics, averaging 49 members/cluster at the end of 2020. The growth of large clusters was related to forward transmission cascades of untreated early-stage infections, younger at-risk populations, more transmissible/replicative-competent strains, and changing demographics. Subtype B and non-B subtype infections introduced through recent migration now surpass the domestic epidemic amongst MSM. Phylodynamics can assist in predicting and responding to active, recurrent, and newly emergent large cluster networks, as well as the cryptic spread of HIV introduced through migration.

Temporal Variation in One-Time Partnership Rates Among Young Men Who Have Sex With Men and Transgender Women.

Volatility in sexual contact rates has been recognized as an important factor influencing HIV transmission dynamics. One-time partnerships may be particularly important given the potential to quickly accumulate large number of contacts. Yet, empirical data documenting individual variation in contact rates remain rare. This study provides much needed data on temporal variation in one-time partners to better understand behavioral dynamics and improve the accuracy of transmission models. Data for this study were obtained from a longitudinal cohort study of young men who have sex with men and transgender women in Chicago. Participants provided sexual network data every 6 months for 2 years. A series of random effects models examined variation in one-time partnership rates and disaggregated within and between associations of exposure variables. Exposure variables included prior number of one-time partners, number of casual partners, and having a main partner. Results indicated substantial between-person and within-person variation in one-time partners. Casual partnerships were positively associated and main partnerships negatively associated with one-time partnership rates. There remained a small positive association between prior one-time partnerships and the current number of one-time partnerships. Despite the preponderance of a low number of one-time partners, substantial variation in one-time partnership rates exists among young men who have sex with men and transgender women. Accordingly, focusing on high contact rate individuals alone may be insufficient to identify periods of highest risk. Future studies should use these estimates to more accurately model how volatility impacts HIV transmission and better understand how this variation influences intervention effectiveness.

Reductions in HIV incidence are likely to increase the importance of key population programmes for HIV control in sub-Saharan Africa.

IntroductionAn efficient HIV response requires that resources be focussed on effective interventions for those most at risk of acquiring and transmitting infection. As HIV epidemics evolve the distribution of HIV across key and other populations will change. Here, the epidemiological concepts underpinning these changes are described and the importance of appropriate allocation of effective interventions is discussed.DiscussionIn many sub‐Saharan African countries HIV epidemics have been categorized as “generalized,” and HIV testing, treatment and prevention interventions have focussed on the “general” population. As HIV epidemics are better controlled the relative importance of “key” populations will increase, dominating the ongoing burden of disease and providing the potential for repeated outbreaks of HIV if interventions are relaxed. The basic reproductive number (R0) describes the potential for an infectious disease to spread at the boundary of invasion or elimination, whereas the effective reproduction number (Rt) describes the current potential for spread. Heterogeneity in risk means that while Rt is temporarily below one and prevalence declining, the R0 can remain above one, preventing eventual elimination. Patterns of HIV acquisition are often used to guide interventions but inadequately capture the transmission dynamics of the virus and the most efficient approach to controlling HIV. Risks for HIV acquisition are not identical to risks for HIV transmission and will change depending on the epidemiological context. In addition to the challenges in measuring HIV transmission dynamics, there is a tension between using epidemiology to drive the HIV response and the social and political realities constraining how programmes and providers can practically and appropriately focus on key populations and maintain political support. In addition to being well focussed, interventions need to be effective and cost‐effective, which requires a better understanding of packages of interventions rather than specific tools.ConclusionsContinued control of HIV will increasingly rely on resources, programmes and interventions supporting key populations. Current epidemiological and programmatic approaches for key populations in sub‐Saharan Africa are insufficient with a need for an improved understanding of local epidemiology and the effectiveness of interventions.

The Role of Phylogenetics in Discerning HIV-1 Mixing among Vulnerable Populations and Geographic Regions in Sub-Saharan Africa: A Systematic Review.

To reduce global HIV-1 incidence, there is a need to understand and disentangle HIV-1 transmission dynamics and to determine the geographic areas and populations that act as hubs or drivers of HIV-1 spread. In Sub-Saharan Africa (sSA), the region with the highest HIV-1 burden, information about such transmission dynamics is sparse. Phylogenetic inference is a powerful method for the study of HIV-1 transmission networks and source attribution. In this review, we assessed available phylogenetic data on mixing between HIV-1 hotspots (geographic areas and populations with high HIV-1 incidence and prevalence) and areas or populations with lower HIV-1 burden in sSA. We searched PubMed and identified and reviewed 64 studies on HIV-1 transmission dynamics within and between risk groups and geographic locations in sSA (published 1995–2021). We describe HIV-1 transmission from both a geographic and a risk group perspective in sSA. Finally, we discuss the challenges facing phylogenetic inference in mixed epidemics in sSA and offer our perspectives and potential solutions to the identified challenges.

Sociometric Risk Network Structure, HIV Prevalence, and Drug Injection-Related Norms among People Who Inject Drugs (PWID) in Athens, Greece

Background: Structural properties of sociometric networks have been associated with behaviors related to HIV transmission. Very few studies, however, have explored the correlation between sociometric network factors and drug injection-related norms. Methods: This exploratory work: (i) describes basic structural qualities of a sociometric risk network of participants in the Transmission Reduction Intervention Project (TRIP) in Athens, Greece, in the context of a large HIV outbreak among people who inject drugs (PWID); (ii) measures HIV prevalence within specific structures within the sociometric risk network of PWID in TRIP; and (iii) explores the association of structural properties of the sociometric risk network in TRIP with drug injection-related norms. Results: The sociometric risk network in TRIP consisted of a large component (n = 241, 67.8%), a few small components (n = 36, 10.1%) with 2-10 individuals each, and some isolates (n = 79, 22.2%). HIV prevalence was significantly higher in the large component (55.6%), the 2-core (59.1%) and 3-core (66.3%) of the large component, and the 3-cliques of the cores. Drug injection-related norms were significantly associated with structural characteristics of the sociometric risk network. A safe behavioral pattern (use of unclean cooker/filter/rinse water was never encouraged) was significantly (p = 0.03) less normative among people who TRIP participants of the 2-core injected with (40.5%) than among network contacts of TRIP participants outside the 2-core (55.6%). On the contrary, at drug-using venues, 2-core members reported that safer behaviors were normative compared to what was reported by those without 2-core membership. Conclusions: Sociometric network data can give useful insights into HIV transmission dynamics and inform prevention strategies. Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.1914103 .

Transmission dynamics and molecular characterization of HIV-1 epidemic among therapeutic failure patients in Santa Catarina state, southern Brazil.

The HIV-1 epidemic in southern Brazil is mostly caused by subtype C, which contrasts the dominance of subtype B in the other regions of the country. Santa Catarina (SC), although the smallest state in the southern region, presents one of the highest incidences and mortality rates in Brazil due to AIDS. This work investigated the HIV-1 molecular diversity and phylogenetic transmission networks in SC state by analyzing a database of 3070 sequences of the national genotyping service. HIV-1C proved to be the most frequent subtype, with a significant increase in prevalence over time. HIV-1B was observed to be associated with highly educated men, suggesting a compartmentalization from other subtypes. Such observation was confirmed by the high frequency of HIV-1B circulating in MSM transmission networks. Identified transmission clusters were majority composed by individuals living up to 25km away and interstate linkages were mainly between southern neighbor states. In general, individuals between 25 and 40years old and sequences sampled after 2014 were more likely to be in transmission chains, in agreement with the universal treatment protocol launched in 2014. The present study brings new insights about HIV-1 transmission dynamics in southern Brazil.

Concordance of HIV transmission risk factors elucidated using viral diversification rate and phylogenetic clustering.

Background and objectivesAlthough HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, it over-simplifies transmission dynamics and is sensitive to methodology. Complementarily, viral diversification rates can be used to approximate historical transmission rates. Here, we investigated the concordance and sensitivity of HIV transmission risk factors identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate and a combined approach.MethodologyViral sequences from 9848 people living with HIV in British Columbia, Canada, sampled between 1996 and February 2019, were used to infer phylogenetic trees, from which clusters were identified and viral diversification rates of each tip were calculated. Factors associated with heightened transmission risk were compared across models of cluster membership, viral diversification rate, changes in diversification rate, and viral diversification rate among clusters.ResultsViruses within larger clusters had higher diversification rates and lower changes in diversification rate than those within smaller clusters; however, rates within individual clusters, independent of size, varied widely. Risk factors for both cluster membership and elevated viral diversification rate included being male, young, a resident of health authority E, previous injection drug use, previous hepatitis C virus infection or a high recent viral load. In a sensitivity analysis, models based on cluster membership had wider confidence intervals and lower concordance of significant effects than viral diversification rate for lower sampling rates.Conclusions and implicationsViral diversification rate complements phylogenetic clustering, offering a means of evaluating transmission dynamics to guide provision of treatment and prevention services.Lay SummaryUnderstanding HIV transmission dynamics within clusters can help prioritize public health resource allocation. We compared socio-demographic and clinical risk factors associated with phylogenetic cluster membership and viral diversification rate, a historical branching rate, in order to assess their relative concordance and sampling sensitivity.

Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE: HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context

This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, TX, the largest city in the Southern United States. Using 6332 HIV-1 pol sequences from persons newly diagnosed with HIV during the period 2010–2018, we reconstructed HIV-1 transmission clusters, using the HIV-TRAnsmission Cluster Engine (HIV-TRACE); inferred demographic and risk parameters on HIV-1 transmission dynamics by jointly estimating viral transmission rates across racial/ethnic, age, and transmission risk groups; and modeled the degree of network connectivity by using generalized estimating equations (GEE). Our results indicate that Hispanics/Latinos are most vulnerable to the structure of transmission clusters and serve as a bridge population, acting as recipients of transmissions from Whites (3.0 state changes/year) and from Blacks (2.6 state changes/year) as well as sources of transmissions to Whites (1.8 state changes/year) and to Blacks (1.2 state changes/year). There were high rates of transmission and high network connectivity between younger and older Hispanics/Latinos as well as between younger and older Blacks. Prevention and intervention efforts are needed for transmission clusters that involve younger racial/ethnic minorities, in particular Hispanic/Latino youth, to reduce onward transmission of HIV in Houston.

Development and Evaluation of an Online Education-Entertainment Intervention to Increase Knowledge of HIV and Uptake of HIV Testing among Colombian Men Who Have Sex with Men (MSM).

Using a community-based participatory approach, we developed a film to promote HIV testing among young men who have sex with men (MSM) in Bogotá. Using a 5-step process to develop the intervention, we conducted 11 focus groups with MSM (n = 141) to receive community feedback at each step. To evaluate the intervention we recruited 300 young MSM to complete a baseline survey in December 2017. Between February–June 2018, 63 participants watched the film and completed a post-viewing survey, which showed the intervention was acceptable for the target population. Between August–December 2018, 48 MSM who watched the film and 47 who did not (control group) completed a follow-up survey. To obtain preliminary evidence of the efficacy of the intervention, we assessed the main effect of time (baseline vs. follow-up) and the interaction between time and group (intervention vs. control) on HIV testing uptake and intentions, and knowledge of HIV transmission dynamics and HIV-related rights. Knowledge of HIV rights increased from baseline to follow-up in the intervention group only. HIV Knowledge increased for both groups. HIV testing intentions increased significantly more for non-gay-identified men in the intervention group, but the overall effect of the intervention was not significant. Testing uptake did not change.

Molecular Transmission Dynamics of Primary HIV Infections in Lazio Region, Years 2013-2020.

Molecular investigation of primary HIV infections (PHI) is crucial to describe current dynamics of HIV transmission. Aim of the study was to investigate HIV transmission clusters (TC) in PHI referred during the years 2013–2020 to the National Institute for Infectious Diseases in Rome (INMI), that is the Lazio regional AIDS reference centre, and factors possibly associated with inclusion in TC. These were identified by phylogenetic analysis, based on population sequencing of pol; a more in depth analysis was performed on TC of B subtype, using ultra-deep sequencing (UDS) of env. Of 270 patients diagnosed with PHI during the study period, 229 were enrolled (median follow-up 168 (IQR 96–232) weeks). Median age: 39 (IQR 32–48) years; 94.8% males, 86.5% Italians, 83.4% MSM, 56.8% carrying HIV-1 subtype B. Of them, 92.6% started early treatment within a median of 4 (IQR 2–7) days after diagnosis; median time to sustained suppression was 20 (IQR 8–32) weeks. Twenty TC (median size 3, range 2–9 individuals), including 68 patients, were identified. A diagnosis prior to 2015 was the unique factor associated with inclusion in a TC. Added value of UDS was the identification of shared quasispecies components in transmission pairs within TC.

Using phylogenetic surveillance and epidemiological data to understand the HIV-1 transmission dynamics in French Guiana.

The aim of this study was to understand the transmission dynamics of the HIV-1 subtype B epidemic in French Guiana and the factors that shaped the expansion of major phylogenetic transmission clusters. HIV-1 subtype B pol sequences with associated epidemiological data obtained from 703 treatment-naive patients living in French Guiana between 2006 and 2012, which correspond to 91% of all HIV cases diagnosed in that period, were employed in this study. Maximum likelihood and Bayesian methods were used to construct phylogenetic trees, identify transmission clusters and estimate intervals between successive infections. Statistical analysis was performed to evaluate epidemiological characteristics associated with cluster membership. HIV-1 subtype B pol sequences from French Guiana were distributed in 10 large/medium transmission clades (LMTC, n > 10, 55%), 19 small transmission clades (STC, n = 3-8, 10%), 36 dyads (10%) or were nonclustered (25%). The rate of clustering did not differ by sex or clinical stage, but sex workers, crack-cocaine users, young individuals (15-20 years) and nationals or migrants from neighbouring South American countries were more likely to cluster within LMTC than individuals from other groups. We estimated that 53-63% of immigrants were infected after the arrival in French Guiana and that 50% of HIV transmissions within LMTC occurred during the first 2 years after infection. These findings reinforce the notion that high-risk sexual behaviours among young individuals and migrants (postmigration) combined with late HIV diagnosis are key drivers of onward dissemination of major HIV transmission clusters in French Guiana.

Mathematical model for transmission dynamics of HIV and tuberculosis co-infection in Kogi State, Nigeria

In this work, we formulated a deterministic co-infection mathematical model made up of a system of nonlinear differential equations and rigorously analyzed it so as to gain insight into the transmission dynamics of each of the diseases as they were co-circulating in the population. We investigated the existence and stability of equilibria of the co-infection model and we subjected the model to rigorous analysis. The analysis of the sub-models (HIV only and TB-only models) and that of the co-infection model revealed that their disease-free equilibrium are locally and globally asymptotically stable when their reproduction numbers were each less than unity, showing that the diseases can be put under control under these conditions. We carried out sensitivity analysis of the co-infection model, using data relevant to Kogi state of Nigeria, which revealed that the top ranked parameters that drive the tuberculosis infection (with respect to the associated response function RT) is (u1), the control measure, educational awareness for the susceptible to always cover their mouth when coughing, sneezing and the need for the infants to be inoculated against the disease, while the top ranked parameter that drive the HIV infection (with respect to the associated response function RH) is (u2), the educational awareness campaign measure for the susceptible individuals to practice safe sexual activities, the need to avoid contacts with bodily fluids of infected patients and the prevention of vertical transmission of the disease. From the simulation of the co-infection model, the phenomenon of competitive exclusion occur where the disease with higher reproduction number drives out that with lesser one; furthermore, it was revealed that increasing the treatment rates of the individuals co-infected with TB and HIV could bring down the burden of the two diseases significantly, while increasing the control measures (u1) and (u2) leads to significant reduction in the cumulative co-infection new cases of mixed infection in the population.

Infer HIV transmission dynamics from gene sequences among young men who have sex with men in China.

To investigate the transmission dynamics and temporal and spatial migration characteristics of HIV spread among men who have sex with men (MSM) in China, a total of 1012 HIV-1 partial pol sequences, including five subtypes, were studied. Bayesian analysis were applied for each subtype to infer its dynamic characters including the effective reproductive number (Re) and migration process. The mean curve of each Re was almost always greater than 1 (even the 95% highest posterior density (HPD) lower value) along with time, which supports the necessity for a comprehensive study about risk behaviors among young MSM group in China. We also should reappraise the free treatment strategy, especially the therapeutic effect during the free treatment policy.

Analyzing the Effectiveness of HIV Prevention and Treatments through a Mathematical Model in Simulated Populations

An epidemiological model for the transmission of HIV/AIDS was developed to analyze the transmission dynamics of HIV in a simulated population. Differential equations derived from the model will be used to show the effectiveness of various treatments and preventative measures used to prevent further spreading of HIV in susceptible populations. Additionally, separate simulations for each of the WHO regions were included to view the spread of HIV on a more focused level rather than on broad global terms to account for regional differences in cases of HIV per capita. HIV data used for the simulations are pulled from WHO’s population data and treatment data was taken from various clinical studies. The results of the simulations show that the world basic reproduction number is 3.33, but regional numbers range from 1.14 to 2.98. We found that post exposure prophylaxis was far more effective at preventing the spread of HIV compared to treatment to viral suppress the infection. Also, without the use of quality post exposure prophylaxis, HIV infections could grow rapidly in the coming years.

Exploring associations between place of sex work and HIV vulnerabilities among sex workers in Jamaica.

Sex workers' work environment shapes HIV transmission dynamics. We applied the Structural HIV Determinants Framework to examine associations between the work environment of public spaces and HIV infection risks among sex workers in Jamaica, considering macro-structural (police harassment) and intrapersonal (depression) pathways. We implemented a cross-sectional survey with sex workers in Kingston, Ocho Rios, Montego Bay, and nearby towns in Jamaica. We conducted structural equation modeling to examine direct and indirect associations between place of sex work on HIV serostatus via mediators of police harassment and depression. Results indicate that public place of sex work had a significant indirect effect on self-reported HIV-positive serostatus; depression and police harassment mediated this relationship. Findings suggest that in contexts of criminalization, the sex work environment can elevate exposure to police violence and depression, in turn increasing HIV vulnerabilities.

Simulating HIV Transmission Dynamics and Predicting the Impact of Testing Policies in Men Who Have Sex with Men in the UK, France, and Poland

Simulating HIV Transmission Dynamics and Predicting the Impact of Testing Policies in Men Who Have Sex with Men in the UK, France, and Poland

Calibration of individual-based models to epidemiological data: A systematic review.

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy-either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures.

Undetectable viral load and HIV transmission dynamics on an individual and population level: where next in the global HIV response?

To examine recent literature on the efficacy and effectiveness of HIV treatment in preventing HIV transmission through sexual exposure, at both an individual and at a population level. Two recent studies on the individual-level efficacy of treatment as prevention (TasP) have added to the now conclusive evidence that HIV cannot be transmitted sexually when the virus is suppressed. However, four large cluster-randomized population-level trials on universal HIV testing and treatment in Africa have not delivered the expected impact in reducing HIV incidence at a population level. Two of these trials showed no differences in HIV incidence between the intervention and control arms, one demonstrated a nonsignificant lower incidence in the intervention arm, and the fourth trial found a reduction between the communities receiving a combination prevention package and the control arm, but no difference between the immediate treatment plus the prevention package and the control arm. Factors contributing to the disconnect between individual high-level efficacy and population-level effectiveness of TasP include undiagnosed infection, delays in linkage to care, challenges in retention and adherence to antiretroviral therapy (ART), time between ART initiation and viral suppression, and stigma and discrimination. Suppressive ART renders people living with HIV sexually noninfectious. However, epidemic control is unlikely to be achieved by TasP alone.