Replacement feeding and the HIV Diaspora: A case of ontological multiplicity and fluid technologies.

Breastmilk is a transmission source of HIV. Therefore, mothers living with HIV are able to avoid exposing their infants to HIV-contaminated breastmilk if they replacement feed them. This article draws on an ethnographic study of an acute National Health Service HIV specialist antenatal clinic in London and explores the ontological multiple HIVs that the practice of replacement feeding takes part in enacting within the fluid space of the HIV diaspora. The term articulates the circumstances of racialised people affected by HIV who are originally from countries where access to life sustaining medication, care and resources-that enable a decoupling of the illness from death-are not readily accessible, and who have (temporarily) relocated themselves to geographical places where these resources are on offer. Arguing that Black African and Caribbean migrant women's ability to benefit from the technologies and care that have turned HIV into a chronic illness in England is delimited by race and their diasporic positionality. In so doing, the article contributes to Sociology by showing how race is part of practice-ethnographic research and medical care even when it is seemingly absent.

'The King of Diseases': An Essay on the Special Attention Paid to Cancer Patients and How It Came About.

The history of cancer during the twentieth century demonstrates that various factors have contributed to the perception of cancer as the 'Emperor of All Maladies', although this has never been true from an epidemiological perspective. Depending on the geographical area, infectious diseases such as tuberculosis, malaria or cardiovascular disease still head the list of the most common illnesses. Within the group of chronic-degenerative diseases, however, cancer has outdistanced the widespread classic infectious diseases as a result of the epidemiologic transition around 1900, at least in the more developed countries. Under the Nazi dictatorship from 1933 to 1945, the perception of cancer in Germany was particularly promoted for propaganda purposes. In the atomic era, cancer began to attract strong public interest as a worthwhile object of research in radiation therapies using large-scale facilities (electron accelerators, 'electron guns'). A further upsurge of interest in cancer was then registered in the context of the debate about the pathogenic role of environmental factors. The remarkable thing is that this increased perception of cancer has not yet been significantly associated with any overarching success in cancer treatment, but it has been associated with ideologies, hopes and advances in technology.

Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States. METHODS: The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription. RESULTS: Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA. CONCLUSIONS: In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

Structural Insights to Human Immunodeficiency Virus (HIV-1) Targets and Their Inhibition.

Human immunodeficiency virus (HIV) is a deadly virus that attacks the body's immune system, subsequently leading to AIDS (acquired immunodeficiency syndrome) and ultimately death. Currently, there is no vaccine or effective cure for this infection; however, antiretrovirals that act at various phases of the virus life cycle have been useful to control the viral load in patients. One of the major problems with antiretroviral therapies involves drug resistance. The three-dimensional structure from crystallography studies are instrumental in understanding the structural basis of drug binding to various targets. This chapter provides key insights into different targets and drugs used in the treatment from a structural perspective. Specifically, an insight into the binding characteristics of drugs at the active and allosteric sites of different targets and the importance of targeting allosteric sites for design of new-generation antiretrovirals to overcome complex and resistant forms of the virus has been reviewed.

Cost estimation of a school-based intervention for improving HIV/AIDS risk perception among secondary school adolescents in Enugu State, Nigeria.

Early sexual debut is common in Nigeria and increases HIV risk among adolescents. About 152,000 adolescents are living with HIV. Lack of knowledge and appropriate sexual reproductive health services are some factors responsible. This paper estimated the cost of secondary school-based HIV/AIDS intervention for schools in Enugu State, Nigeria. The rationale for estimation is to avoid unaffordable and ineffective interventions. The cost was estimated between March to October 2019 for schools in urban and rural areas with population of 1595 students. The cost estimation was aided through UNAID proposed guideline. The estimation was done by classifying intervention into cost of training, cost of services and cost of commodities. The cost was estimated at $5954. The estimated cost in urban is lesser than that of rural. This estimated cost of intervention may inform stakeholders with the knowledge of cost implications to avoid unaffordable school-based HIV interventions in Enugu State, Nigeria.

Risk Factors Associated with HIV, Sexually Transmitted Infections (STI), and HIV/STI Co-infection Among Youth Living in the Slums of Kampala, Uganda.

The purpose of this analysis was to examine the associated factors of self-reported HIV/STI co-infection among youth living in the slums of Kampala. The study sample consists of a cross-sectional survey. Participants comprised a convenience sample (N = 1134) of youth living on the streets or in the slums (age 12-18). Multinomial logistic regression analyses were used to determine the association between hypothesized risk factors and levels of HIV/STI co-infection, adjusting for sociodemographic variables. Among the sample of youth who were sexually active (n = 586), 9.9% (n = 58) of youth reported HIV/STI co-infection. Among youth with HIV (13.8%), 71.6% reported a co-infection with another STI. In the multivariable analysis, youth with HIV/STI co-infection were more likely to engage in problem drinking (OR 2.55; 95% CI 1.08, 6.02) and drinking alcohol without problematic alcohol behavior (OR 3.43; 95% CI 1.60, 7.36). HIV/STI co-infection rates are high among youth living in the slums of Kampala and warrant urgent attention.

Psychosocial correlates of self-reported HIV among youth in the slums of Kampala.

BACKGROUND: Human immunodeficiency virus (HIV) rates are high in Uganda (6.7%), and rates are especially high among at-risk groups such as youth living in the slums of Kampala, Uganda. The objective of this study was to assess the psychosocial correlates, particularly alcohol use, associated with HIV among youth living in the slums of Kampala, Uganda. METHODS: Analyses are based on cross-sectional survey data collected in Spring of 2014. Participants comprised a convenience sample (N = 1134) of urban service-seeking youth living on the streets or in the slums, 12-18 years of age who were participating in a Uganda Youth Development Link drop-in center (56.1% female and 43.9% male). Chi-Square Tests were used to determine differences in the proportions of alcohol use patterns between self-reported HIV-positive and HIV-negative youth. Bivariate and multivariable logistic regression were conducted to determine the associated risk factors with self-reported HIV. Institutional Review Board approvals were obtained from the Georgia State University and the Uganda National Council for Science and Technology. RESULTS: Among the total sample of youth (N = 1103), 10.5% (n = 116) reported being HIV-positive. There were statistically significant differences between HIV-positive and HIV-negative youth on ever living on the streets (χ2 =10.14, df = 1, p = 0.002), past 12-month alcohol use (χ2 =16.38, df = 1, p < .0001), ever having sexual intercourse (χ2 =14.52, df = 1, p = 0.0001), ever engaging in sex work (χ2 =13.19, df = 1, p = 0.0003), inconsistent condom use in the past 3 months (χ2 =5.03, df = 1, p = 0.03), and ever being raped (χ2 =15.29, df = 1, p < 0.0001). A higher percentage of HIV-positive youth were classified as problem drinkers, defined by the CAGE scores (21.6% vs. 13.9%, respectively). In the multivariable analysis, previously being raped (OR: 1.70; 95% CI: 1.02, 2.83) and alcohol use without problem drinking (OR: 2.14; 95% CI: 1.24, 3.69) was associated with HIV. CONCLUSION: Youth living in the slums of Kampala, Uganda have a high prevalence of HIV. These youth are in dire need of interventions which address both alcohol use behaviors and sexual risk behaviors to reduce further complications of their existing health conditions, including HIV.

Everyday and unavoidable coproduction: exploring patient participation in the delivery of healthcare services.

The financial and capacity pressures facing healthcare systems call for new strategies to deliver high-quality, efficient services. 'Coproduction' is a concept gaining recognition as an approach to create patient partnerships that enable better functioning healthcare systems. Yet, this framing obscures coproduction's 'everyday and unavoidable' character, already part of healthcare service delivery. This paper aims to understand these everyday and unavoidable dimensions of coproduced healthcare services by drawing upon thematic and process analyses of a 15-month ethnography of 45 patients in three HIV clinics in New York. A 'health practices' approach guided exploring patients' activities, their effects on clinical processes, and the conditions surrounding their performances. By constructing a typology of activity types - Building, Accepting, and Objecting - and tracing patients' descriptions of activity performances, the paper shows how coproduction is forged by making and relying upon clinic-based relationships, and for patients also with a broader human community. These dynamics reveal how patients' bodily and temporal understandings are brought into and shape coproduced services. From these insights, we recommend that healthcare practitioners incorporate into their coproduction analytic methods and perspectives to engage patients as capable and aware individuals, who can support clinic efficiencies while producing new delivery possibilities.

A Livelihood Intervention to Reduce the Stigma of HIV in Rural Kenya: Longitudinal Qualitative Study.

The scale-up of effective treatment has partially reduced the stigma attached to HIV, but HIV still remains highly stigmatized throughout sub-Saharan Africa. Most studies of anti-HIV stigma interventions have employed psycho-educational strategies such as information provision, counseling, and testimonials, but these have had varying degrees of success. Theory suggests that livelihood interventions could potentially reduce stigma by weakening the instrumental and symbolic associations between HIV and premature morbidity, economic incapacity, and death, but this hypothesis has not been directly examined. We conducted a longitudinal qualitative study among 54 persons with HIV participating in a 12-month randomized controlled trial of a livelihood intervention in rural Kenya. Our study design permitted assessment of changes over time in the perspectives of treatment-arm participants (N = 45), as well as an understanding of the experiences of control arm participants (N = 9, interviewed only at follow-up). Initially, participants felt ashamed of their seropositivity and were socially isolated (internalized stigma). They also described how others in the community discriminated against them, labeled them as being "already dead," and deemed them useless and unworthy of social investment (perceived and enacted stigma). At follow-up, participants in the treatment arm described less stigma and voiced positive changes in confidence and self-esteem. Concurrently, they observed that other community members perceived them as active, economically productive, and contributing citizens. None of these changes were noted by participants in the control arm, who described ongoing and continued stigma. In summary, our findings suggest a theory of stigma reduction: livelihood interventions may reduce internalized stigma among persons with HIV and also, by targeting core drivers of negative attitudes toward persons with HIV, positively change attitudes toward persons with HIV held by others. Further research is needed to formally test these hypotheses, assess the extent to which these changes endure over the long term, and determine whether this class of interventions can be implemented at scale.

Syndemics and Health Disparities: A Methodological Note.

In the theory of syndemics, diseases are hypothesized to co-occur in particular temporal or geographical contexts due to harmful social conditions (disease concentration) and to interact at the level of populations and individuals, with mutually enhancing deleterious consequences for HIV risk (disease interaction). Since its original elaboration more than 20 years ago, the epidemiological literature on syndemic problems has followed a questionable trajectory, stemming from the use of a specific type of regression model specification that conveys very little information about the theory of syndemics. In this essay we critically review the dominant approaches to modeling in the literature on syndemics; highlight the stringent assumptions implicit in these models; and describe some meaningful public health implications of the resulting analytical ambiguities. We conclude with specific recommendations for empirical work in this area moving forward.

Women's experience of HIV as a chronic illness in South Africa: hard-earned lives, biographical disruption and moral career.

This article presents findings from a longitudinal qualitative study (48 in-depth interviews with 12 women on antiretroviral treatment (ART)) exploring the experience of living with HIV as a chronic illness in South Africa by applying the structural and interactionist perspectives on chronic illness. The structural perspective indicates that the illness experience needs to be contextualised within the wider framework of the women's hard-earned lives: throughout the interviews, the women tended to refuse singularising HIV/AIDS and continuously framed the illness within the context of general hardship and adversity. Employing an interactionist perspective, the repeated interviews demonstrated the partial applicability of the concept of biographical disruption to the illness experience: most women experienced feelings of denial and disbelief upon diagnosis, but the availability of ART clearly mitigated the impact of HIV on their biographies. In addition, our findings demonstrate that the interaction between structural aspects, (stigmatising) social relations, and the illness (and its treatment) determines the never-ending cycle of identity appraisals, revisions and improvements, rendering the moral career of the HIV-positive women on ART a continuous work in progress.

'Treating Africans differently': using skin colour as proxy for HIV risk.

AIMS AND OBJECTIVES: This paper examines the qualitative results of two studies of Black African new settler communities in New Zealand. The analysis investigates the issues of stigma and microaggressions and their effects on Black African communities. BACKGROUND: Previous work that investigated experiences of stigma faced by relatively early Black African new settlers to New Zealand found that new settlers experienced stigma, and their resulting isolation had negative implications for access to health and social services, regardless of HIV status. DESIGN: This paper is a meta-analysis of two published studies, using original qualitative data from each. METHODS: Researchers for the first study, Standing in the Fire, interviewed 13 Black Africans living with HIV who were new settlers to New Zealand. The second study, AfricaNZ Care, was a national mixed method study which surveyed 703 Black African new settlers, and included 131 participants in 23 different focus groups. The present analysis includes only the qualitative data from the second study. Some, but not most, participants of the second study were living with HIV. RESULTS: Black African identity is used as a proxy for HIV status among non-HIV specialist health care workers. Participants reported experiences of stigma and microaggressions based on their race, and a lack of knowledge about HIV in non-HIV specialist nurses and other health care workers. They also experienced poor health care and education practices, professional prejudice against colleagues living with HIV and institutional challenges including failure to protect patient confidentiality. CONCLUSIONS: HIV-related stigma and microaggressions remain significant problems, not only for people living with HIV but also for those perceived to be at high risk for HIV. RELEVANCE TO CLINICAL PRACTICE: Experiences of stigmatising behaviour by health care professionals have a broad and significant range of impacts on patients' health outcomes.

Links between teacher assessment and child self-assessment of mental health and behavior among children affected by HIV/AIDS.

Teachers are considered to be one of the most important influences in the lives of students. Teachers' assessments of students may be a primary source of information on children's mental and behavioral health; however, this topic has received little attention in research. We examined this issue through linking teachers' ratings of students and mental and behavioral outcomes of children affected by HIV. The hypothesis is that teacher ratings will be predictive of specific child mental and behavioral health outcomes. A quantitative cross-sectional design with self-administered paper-and-pencil instruments was used. The sample included 1221 children (aged 6-18, grades 1-11) affected by HIV including 755 orphans who lost one or both parents to AIDS and 466 vulnerable children living with HIV-infected parents in a central province of China. The corresponding teacher sample included 185 participants. Each child completed an assessment inventory of demographic information and mental and behavioral health measures. Teachers completed a questionnaire about children's school performance. SEM analyses revealed a good model fit according to all fit indices: comparative fit index = 0.93, root mean square error of approximation = 0.07, and standardized root mean square residual = 0.04. Structural equation modeling revealed that problem ratings by teachers were positively associated with child loneliness and behavioral problems, social competence ratings by teachers were negatively related to child depression, and personal growth and social interaction ratings by teachers were negatively related to child loneliness, depression, and trauma. The current study represents a unique contribution to the field in that it recognizes that teachers can be a valuable source of information on children's psychological health. Results from this study have implications for health prevention and intervention for children and families suffering from HIV/AIDS.

Lesbian blood drives as community-building activism in the 1980s.

As gay men began voluntarily withdrawing from blood donation in the early 1980s, lesbians in community with gay men in several U.S. cities organized drives to replenish the blood supply. These drives were sometimes the continuation of previously established drives by gay-lesbian organizations or faith communities, sometimes new initiatives in response to HIV/AIDS. However, after the initial publicity, mention of lesbian blood drives in print is both scarce and brief. Focusing on drives organized from 1983 to 1992 by a group known as San Diego Blood Sisters, this article is an initial step in documenting lesbian blood drives to inform and enrich conversations about histories of responses to HIV/AIDS, theoretical discussions of how community connections in the lesbian, gay, bisexual, transgender, and queer spectrum are enacted and understood, and emerging research on intersections of gender and sexuality as they are expressed through blood donorship.

Surrogate markers of visceral adipose tissue in treated HIV-infected patients: accuracy of waist circumference determination.

OBJECTIVES: The accuracy of the use of anthropometrics to quantify visceral adipose tissue (VAT) in treated HIV-infected patients is unknown. We evaluated the predictive accuracy of waist circumference (WC) with and without dual-energy X-ray absorptiometry (DXA)-derived trunk : limb fat ratio [fat mass ratio (FMR)] as surrogates for VAT determined using computerized axial tomography (CT-determined VAT). METHODS: We performed a retrospective cohort analysis of treated HIV-infected male patients followed at the Modena HIV Clinic. We developed prediction equations for VAT using linear regression analysis and Spearman correlations. Receiver operating characteristic (ROC) analysis evaluated the accuracy of WC alone or with FMR at discrete VAT thresholds. RESULTS: The 1500 Caucasian male patients had a median age of 45 years, body mass index (BMI) of 24, WC of 87 cm, VAT area of 127 cm(2) and body fat percentage of 14%. The correlation between WC-predicted VAT and CT-VAT was 0.613, and this increased significantly if FMR was added. The WC-associated R(2) of 0.35 increased to 0.51 if the prediction equation included WC plus FMR. The area under the ROC curve (AUC) using WC was 0.795-0.820 at all VAT thresholds. The positive predictive value (PPV) and negative predictive value (NPV) changed reciprocally at CT-VAT thresholds from 75 to 200 cm(2) and ranged from 0.72 to 0.74, respectively, at a representative VAT of 125 cm(2). Adding the FMR to the predictive equations increased the AUC in the range of 0.854-0.889 with the PPV and NPV increasing minimally, ranging from 0.780 to 0.821. Limits of precision were wide, especially at the highest CT-VAT levels, and varied from 24 to 68 cm(2). CONCLUSIONS: WC is a limited surrogate for CT-VAT in this population and DXA-derived parameters do not improve performance indices to a clinically relevant level. These findings should inform the applicability of WC to predict VAT in treated HIV-infected male patients.

Nurturing compassion through care-giving and care-receiving: the changing moral economy of AIDs in China.

Based on the case study of an Aids clinic operated in Nanning by MSF, this paper looks at how one international NGO, Médecins Sans Frontières (MSF, or Doctors Without Borders), deals with the HIV-carrier patients in Nanning, the capital of Guangxi province in China. It explores the process of care-giving to the HIV patients by MSF employees (both foreign and local) and how the patients react to the 'care-receiving' provided by this foreign NGO. This is especially pertinent in China today as HIV-patients are the victims of discriminating policies and are still very much discriminated by the general population. MSF, viewed by the victims as a foreign NGO, is regarded as an organization seen as promoting a changing and compassionate attitude toward AIDs patients through their anonymous and non-discriminating practices. Through the practices and the discourse of MSF workers and the testimonies of the patients, this paper looks at how the moral economy of AIDs is evolving from a repressive and discriminative attitude towards the compassionate attention to individual suffering. As such, MSF, through its actions, is seen as one of the agents promoting attitudinal changes toward disadvantaged groups and is facilitating the emergence of an emotional and compassionate subject.

Immunotoxin-mediated depletion of Gag-specific CD8+ T cells undermines natural control of SIV.

Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is potentially confounded by several factors, including reactive CD4+ T cell proliferation, and provides no information on epitope specificity, a likely determinant of CD8+ T cell efficacy. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissue-localized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.

Vedolizumab and ART in recent HIV-1 infection unveil the role of α4ß7 in reservoir size.

BACKGROUNDWe evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of α4ß7 on the HIV-1 reservoir size.METHODSParticipants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed.RESULTSVedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, α4ß7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4ß7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4ß7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4ß7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4ß7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe," research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council.

NKG2C and NKG2A Co-expression Defines a Highly Functional Antiviral NK Population in Spontaneous HIV Control.

Elite controllers (EC), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in EC after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+memory-like NK cells. Functional analyses indicated that EC had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, EC showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity (ADCC) adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57 and CXCR3. In-depth single-cell RNA sequencing unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.