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Background Clusters 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. Methods Deidentified 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. Results Geography 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. Conclusions Within 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.

Medical advances in the treatment of HIV over the last 35 years mean that people living with HIV (PLHIV) now have a life expectancy close to that of the general population. Further, when successfully treated, PLHIV cannot transmit the virus. Despite this, HIV-related stigma remains widespread, including within healthcare settings. Stigma is not a vague sociological notion but represents a real threat to public health, with repercussions for both PLHIV and HIV-negative individuals. Stigma has been shown to have a negative impact on HIV prevention, testing, access to health services, and on the healthcare management of PLHIV. Taking stigma into consideration is essential, both in meeting the medical and psycho-social needs of PLHIV and in order to effectively combat HIV/AIDS.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens.METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted.FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain.INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators.FUNDING: Bill & Melinda Gates Foundation.

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence — measured as the rate of decline of CD4+ T cells — and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%–30%), and that of the per-parasite pathogenicity is 17% (4%–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.

BACKGROUND: Sequence data from resistance testing offer unique opportunities to characterize the structure of human immunodeficiency virus (HIV) infection epidemics. METHODS: We analyzed a representative set of HIV type 1 (HIV-1) subtype B pol sequences from 5700 patients enrolled in the Swiss HIV Cohort Study. We pooled these sequences with the same number of sequences from foreign epidemics, inferred a phylogeny, and identified Swiss transmission clusters as clades having a minimal size of 10 and containing >or=80% Swiss sequences. RESULTS: More than one-half of Swiss patients were included within 60 transmission clusters. Most transmission clusters were significantly dominated by specific transmission routes, which were used to identify the following patient groups: men having sex with men (MSM) (38 transmission clusters; average cluster size, 29 patients) or patients acquiring HIV through heterosexual contact (HETs) and injection drug users (IDUs) (12 transmission clusters; average cluster size, 144 patients). Interestingly, there were no transmission clusters dominated by sequences from HETs only. Although 44% of all HETs who were infected between 1983 and 1986 clustered with injection drug users, this percentage decreased to 18% for 2003-2006 (P

Background. Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)–naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. Methods. MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. Results. Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1–infected patients (8.2% vs 2.5%; P = .004). Conclusions. Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin—transmission vs sporadic appearance—of these variants determines their impact on ART needs to be further explored.

Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8–2.1), female gender (OR: 1.6; 95% CI: 1.4–1.7), black ethnicity (OR: 1.9; 95% CI: 1.7–2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6–2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS’. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.

Introduction: Mother-To-Child Transmission of HIV is responsible for more than 90.0% of HIV infections in children, and breastfeeding is one of the common routes of transmission. This study therefore determined factors influencing infant feeding choices of HIV positive mothers enrolled in Prevention of Mother to Child Transmission HIV clinics in Oyo State.Methods: Four Focus Group Discussion (FGDs) sessions were conducted among forty HIV positive mothers with babies between the ages of 6weeks and one year with the aid of an FGD guide. Data was analysed using thematic approach. Findings: More than one –third of the mothers (37.5%) were between the ages of 25-29 years. More than half of the mothers (52.5%) were married in polygamous relationships and almost half of them (47.5 %) completed primary school education. Majority were traders/artisan, two third of them were earning less than ₦18000 per month. Majority of the mothers had good knowledge of infant feeding options in the context of HIV. Majority of the mothers claimed to be practicing exclusive breast feeding due to their low economic status. Fear of disclosure of HIV status and stigma has also weakened the ability of mothers to resist family pressure that encourages mixed feeding practices. Women who chose to exclusively formula feed were the civil servants who were financially capable.Conclusion: Although a high proportion of mothers practiced exclusive breastfeeding, mixed feeding is still being practiced due to family pressure. Family members’ education on safer infant feeding practices and behavioural change programmes in the context of HIV is advocated.Keywords: Infant food; Breast feeding; HIV infections/transmission

Background New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. Methodology/Principal Findings The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. Conclusions/Significance The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

By fusing the green fluorescent protein to their favorite proteins, biologists now have the ability to study living complex cellular processes using fluorescence video microscopy. To track the movements of the human immunodeficiency virus core protein during cell-to-cell transmission of human immunodeficiency virus, we have GFP-tagged the Gag protein in the context of an infectious molecular clone of HIV, called HIV Gag-iGFP. We study this viral clone using video confocal microscopy. In the following visualized experiment, we transfect a human T cell line with HIV Gag-iGFP, and we use fluorescently labeled uninfected CD4+ T cells to serve as target cells for the virus. Using the different fluorescent labels we can readily follow viral production and transport across intercellular structures called virological synapses. Simple gas permeable imaging chambers allow us to observe synapses with live confocal microscopy from minutes to days. These approaches can be used to track viral proteins as they move in from one cell to the next.

Background Used in conjunction with biological surveillance, behavioural surveillance provides data allowing for a more precise definition of HIV/STI prevention strategies. In 2008, mapping of behavioural surveillance in EU/EFTA countries was performed on behalf of the European Centre for Disease prevention and Control. Method Nine questionnaires were sent to all 31 member States and EEE/EFTA countries requesting data on the overall behavioural and second generation surveillance system and on surveillance in the general population, youth, men having sex with men (MSM), injecting drug users (IDU), sex workers (SW), migrants, people living with HIV/AIDS (PLWHA), and sexually transmitted infection (STI) clinics patients. Requested data included information on system organisation (e.g. sustainability, funding, institutionalisation), topics covered in surveys and main indicators. Results Twenty-eight of the 31 countries contacted supplied data. Sixteen countries reported an established behavioural surveillance system, and 13 a second generation surveillance system (combination of biological surveillance of HIV/AIDS and STI with behavioural surveillance). There were wide differences as regards the year of survey initiation, number of populations surveyed, data collection methods used, organisation of surveillance and coordination with biological surveillance. The populations most regularly surveyed are the general population, youth, MSM and IDU. SW, patients of STI clinics and PLWHA are surveyed less regularly and in only a small number of countries, and few countries have undertaken behavioural surveys among migrant or ethnic minorities populations. In many cases, the identification of populations with risk behaviour and the selection of populations to be included in a BS system have not been formally conducted, or are incomplete. Topics most frequently covered are similar across countries, although many different indicators are used. In most countries, sustainability of surveillance systems is not assured. Conclusion Although many European countries have established behavioural surveillance systems, there is little harmonisation as regards the methods and indicators adopted. The main challenge now faced is to build and maintain organised and functional behavioural and second generation surveillance systems across Europe, to increase collaboration, to promote robust, sustainable and cost-effective data collection methods, and to harmonise indicators.

Background Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs. Results All recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell–cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment. Conclusions With the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic. Electronic supplementary material The online version of this article (doi:10.1186/s12977-016-0299-0) contains supplementary material, which is available to authorized users.

L'étude a développé deux axes de recherche: dans le premier, elle a visé à connaître comment les intervenants en toxicomanie appréhendent leurs tâches de prévention de la transmission sexuelle du VIH/sida (PST), quels sont les problèmes qu'ils rencontrent et comment ils pourraient mieux y faire face. Dans le deuxième axe, l'étude avait pour but de mieux connaître les expériences vécues par les consommateurs de drogues dans leur recherche de conseils concernant la prévention de la transmission sexuelle du VIH/sida et leurs besoins à ce sujet. L'attention a aussi été données aux difficultés que rencontrent les consommateurs de drogues à suivre des consignes de prévention dans le domaine de la transmission sexuelle du VIH/sida en tenant compte des différences entre hommes et femmes. [Table des matières] 1. Résumé : synthèse des focus groups, des interviews, conclusions et recommandations. 2. Rappel de la stratégie de prévention et des 3 niveaux d'intervention. 3. Etat de la recherche dans le domaine. 4. Données épidémiologiques VIH/sida. 5. Utilisation du préservatif. 6. Intervenants en toxicomanie, formation , problèmes décrits. 7. Consommateurs de drogues, sexualité, prévention du VIH. 8. Méthodologie. 9. Focus groups avec les intervenants en toxicomanie. 10. Transcription et codification des focus groups. 11. Composition des focus groups et représentativité. 12. Interviews semi-directives des consommateurs de drogues. 13. Construction de la grille d'entretien pour les interviews. 14. Résultats des focus groups. 15. Analyse. 16. Représentations de la prévention de la transmission sexuelle du VIH/sida (PST). 17. Pratiques de PST effectives. 18. Difficultés à faire de la PST. 19. Propositions d'amélioration. 20. Synthèse des propositions des intervenants. 21. Résultats des interviews des consommateurs de drogue. 22. Représentation de la PST. 23. Pertinence des consignes de prévention. 24. Pratiques de prévention vécues. 25. Activité sexuelle. 26. Type de partenaire. 27. Parcours de vie affective et sexuelle. 28. Utilisation du préservatif. 29. Influence de la consommation sur la sexualité. 30. Synthèse sur les pratiques. 31. Difficultés. 32. Conditions de vie. 33. Désespoir et estime de soi. 34. Consommation de cocaïne. 35. Transmission sexuelle du VIH et transmission par voie intraveineuse. 36. Prostitution. 37. Synthèse des difficultés. 38. Synthèse sur les expériences de discussion sur la PST. 39. Synthèse sur les propositions d'amélioration. 40. Synthèse des interviews. 41. Grille d'entretien pour les focus groups, pour les interviews des consommateurs de drogue. 42. Questionnaire court pour les consommateurs de drogue.

[Table des matières] I. Résumé. II. Zusammenfassung. III. Méthodes. 1. Entretiens avec des intervenants. 2. Entretiens avec les personnes vivant avec le VIH. IV. Analyse de la littérature. 1. Aspects généraux liés au VIH. 2. Aspects de la vie sexuelle influencés par le VIH. 3. Counselling. V. Intervenants. 1. Perception de soi. 2. Désir. 3. Recherche de partenaire(s). 4. Relations de couple. 5. Activité sexuelle. 6. Activité sexuelle dans les couples stables. 7. Activité sexuelle chez les personnes sans partenaire stable. 8. Responsabilité de la protection. 9. Désir d'enfant / procréation. VI. Personnes vivant avec le VIH. 1. Perception de soi. 2. Nouer une relation. 3. Maintenir une relation. 4. Adéquation de l'offre de prise en charge dans le domaine de la sexualité. VII. Discussion et conclusions. 1. Conséquences du VIH/sida sur la vie affective et sexuelle des personnes infectées. 2. Résultats de la "triangulation" de l'information. 3. Conséquences en termes de santé publique.

Purpose: The use of bone allografts involves the risk of transmitting infectious agents from the donor to the recipient as shown by historical surveys. A study was therefore undertaken to test the hypothesis that human immunodeficiency virus (HIV) activity can still be present after the freezing and thawing of ribs taken from an acquired immune deficiency syndrome (AIDS) patient at autopsy. Materials and Methods: Rib samples were harvested under sterile conditions and frozen at −80 °C. After different freezing periods, the samples were cultured with activated lymphocytes. P24 antigen determination in the supernatant fluid was used to test for viral activity. Results: Confirmation of viral activity was obtained after freezing periods ranging from 1 to 12 weeks. Conclusions: HIV activity can be found in ribs of AIDS patients, and this outlives the cryoprotection of bone banking. Donor selection remains the main security in the use of frozen bone allografts.

Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health. In this study, we develop a phylogeny-based statistical approach to address this question. As a case study, we use this to investigate the trends and determinants of HIV transmission among Swiss heterosexuals. We extract the corresponding transmission clusters from a phylogenetic tree. To capture the incomplete sampling, the delayed introduction of imported infections to Switzerland, and potential factors associated with basic reproductive number R0, we extend the branching process model to infer transmission parameters. Overall, the R0 is estimated to be 0.44 (95%-confidence interval 0.42—0.46) and it is decreasing by 11% per 10 years (4%—17%). Our findings indicate rather diminishing HIV transmission among Swiss heterosexuals far below the epidemic threshold. Generally, our approach allows to assess the danger of self-sustained epidemics from any viral sequence data., eLife digest In epidemiology, the “basic reproductive number” describes how efficiently a disease is transmitted, and represents the average number of new infections that an infected individual causes. If this number is less than one, many people do not infect anybody and hence the transmission chains die out. On the other hand, if the basic reproductive number is larger than one, an infected person infects on average more than one new individual, which leads to the virus or bacteria spreading in a self-sustained way. Turk et al. have now developed a method to estimate the basic reproductive number using the genetic sequences of the virus or bacteria, and have used it to investigate how efficiently HIV spreads among Swiss heterosexuals. The results show that the basic reproductive number of HIV in this group is far below the critical value of one and that over the last years this number has been decreasing. Furthermore, the basic reproductive number differs for different subtypes of the HIV virus, indicating that the geographical region where the infection was acquired may play a role in transmission. Turk et al. also found that people who are diagnosed later or who often have sex with occasional partners spread the virus more efficiently. These findings might be helpful for policy makers as they indicate that the risk of self-sustained transmission in this group in Switzerland is small. Furthermore the method allows HIV epidemics to be monitored at high resolution using sequence data, assesses the success of currently implemented preventive measures, and helps to target subgroups who are at higher risk of an infection – for instance, by supporting frequent HIV testing of these people. The method developed by Turk et al. could also prove useful for assessing the danger of other epidemics.