Search

: Introduction: Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non‐immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk. Discussion: STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub‐mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue‐resident cells that may also display innate‐like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert. Conclusions: STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under‐appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub‐clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection., Introduction There are over 50 types of viruses, bacteria and parasites that can be sexually transmitted, eight of which are most widely recognized as sexually transmitted infections (STIs). These include [...]

CD4+ T cells expressing α4β7 play an important role in HIV pathogenesis. Indicative integrins in HIV: The gut is thought to be a major viral reservoir in HIV infection, and studies in nonhuman primates suggest that targeting the α4β7 integrin on T cells may be a viable therapy. Sivro et al. now extend these findings to humans by examining HIV acquisition in multiple African cohorts. Higher frequencies of α4β7+ circulating CD4+ T cells before infection were associated with increased HIV acquisition, viral load at set point, and more rapid CD4+ T cell decline. These exciting data confirm that integrin targeting could help reduce the spread of HIV. The gastrointestinal (GI) mucosa is central to HIV pathogenesis, and the integrin α4β7 promotes the homing of immune cells to this site, including those that serve as viral targets. Data from simian immunodeficiency virus (SIV) animal models suggest that α4β7 blockade provides prophylactic and therapeutic benefits. We show that pre-HIV infection frequencies of α4β7+ peripheral blood CD4+ T cells, independent of other T cell phenotypes and genital inflammation, were associated with increased rates of HIV acquisition in South African women. A similar acquisition effect was observed in a Kenyan cohort and in nonhuman primates (NHPs) after intravaginal SIV challenge. This association was stronger when infection was caused by HIV strains containing V2 envelope motifs with a preference for α4β7 binding. In addition, pre-HIV α4β7+ CD4+ T cells predicted a higher set-point viral load and a greater than twofold increased rate of CD4+ T cell decline. These results were confirmed in SIV-infected NHPs. Increased frequencies of pre-HIV α4β7+ CD4+ T cells were also associated with higher postinfection expression of lipopolysaccharide binding protein, a microbial translocation marker, suggestive of more extensive gut damage. CD4+ T cells expressing α4β7 were rapidly depleted very early in HIV infection, particularly from the GI mucosa, and were not restored by early antiretroviral therapy. This study provides a link between α4β7 expression and HIV clinical outcomes in humans, in line with observations made in NHPs. Given the availability of a clinically approved anti-α4β7 monoclonal antibody for treatment of inflammatory bowel disease, these data support further evaluation of targeting α4β7 integrin as a clinical intervention during HIV infection. [ABSTRACT FROM AUTHOR]

An abstract of the article "Correlates of Adherence and Antiretroviral Treatment Failure in HIV-1 Infected Kenyan Patients" by Rose C. Kitawi, Timothy J. Nzomo, Charity Hungu and colleagues is presented.

Background: The design of HIV prevention programs for adolescent girls and young women (AGYW) are informed by data on who is at highest risk and where they can be reached. Places (hotspots) associated with selling sex are an established outreach strategy for sex work (SW) programs but could be used to reach other AGYW at high risk., Setting: This study took place in Mombasa, Kenya., Methods: We conducted a cross-sectional, bio-behavioural survey among (N = 1193) sexually active AGYW aged 14-24 years recruited at hotspots. We compared HIV prevalence by subgroup (SW; transactional sex, TS; and non-transactional sex), stratified by hotspot type (venues and nonvenues). We examined whether associations between HIV prevalence and hotspot/subgroup remained after adjustment for individual-level risk factors, and estimated HIV prevalence ratio with and without adjustment for these individual-level factors., Results: Overall HIV prevalence was 5.6%, 5.3% in venues and 7.3% in nonvenues. Overall SW HIV prevalence was 2-fold higher than among participants engaged in nontransactional sex. After adjusting for age and individual-level risk factors, HIV prevalence was 2.72 times higher among venue-based SWs (95% confidence interval: 1.56 to 4.85) and 2.11 times higher among nonvenue AGYW not engaged in SW (95% confidence interval: 0.97 to 4.30) compared with venue-based AGYW not engaged in SW., Conclusion: AGYW who sell sex remain at high risk of HIV across types of hotspots. The residual pattern of elevated HIV burden by AGWY subgroup and hotspot type suggests that unmeasured, network-level factors underscore differential risks. As such, hotspots constitute a "place" to reach AGYW at high risk of HIV., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although nonoptimal vaginal bacteria and inflammation have been associated with increased HIV risk, the upstream drivers of these phenotypes are poorly defined in young African women., Setting: Mombasa, Kenya., Methods: We characterized vaginal microbiome and cytokine profiles of sexually active young women aged 14-24 years (n = 168) in 3 study groups: those engaging in formal sex work, in transactional sex, and nonsex workers. Vaginal secretions were collected using self-inserted SoftCup, and assayed for cytokines and vaginal microbiome through multiplex ELISA and 16S rRNA sequencing, respectively. Epidemiological data were captured using a validated questionnaire., Results: The median age of participants was 20 years (interquartile range: 18-22 years). Approximately two-thirds of young women (105/168) had vaginal microbial communities characterized by Gardnerella and/or Prevotella spp. dominance; a further 29% (49/168) were predominantly Lactobacillus iners. Microbiome clustering explained a large proportion of cytokine variation (>50% by the first 2 principal components). Age was not associated with vaginal microbial profiles in bivariable or multivariable analyses. Women self-identifying as sex workers had increased alpha (intraindividual) diversity, independent of age, recent sexual activity, HIV, and other sexually transmitted infections (beta = 0.47, 95% confidence interval: 0.05 to 0.90, P = 0.03). Recent sex (number of partners or sex acts last week, time since last vaginal sex) correlated with increased alpha diversity, particularly in participants who were not involved in sex work., Conclusion: Nonoptimal vaginal microbiomes were common in young Kenyan women and associated with sex work and recent sexual activity, but independent of age. Restoring optimal vaginal microflora may represent a useful HIV prevention strategy.

The gastrointestinal (GI) mucosa is central to HIV pathogenesis, and the integrin α 4 β 7 promotes the homing of immune cells to this site, including those that serve as viral targets. Data from simian immunodeficiency virus (SIV) animal models suggest that α 4 β 7 blockade provides prophylactic and therapeutic benefits. We show that pre-HIV infection frequencies of α 4 β 7 + peripheral blood CD4 + T cells, independent of other T cell phenotypes and genital inflammation, were associated with increased rates of HIV acquisition in South African women. A similar acquisition effect was observed in a Kenyan cohort and in nonhuman primates (NHPs) after intravaginal SIV challenge. This association was stronger when infection was caused by HIV strains containing V2 envelope motifs with a preference for α 4 β 7 binding. In addition, pre-HIV α 4 β 7 + CD4 + T cells predicted a higher set-point viral load and a greater than twofold increased rate of CD4 + T cell decline. These results were confirmed in SIV-infected NHPs. Increased frequencies of pre-HIV α 4 β 7 + CD4 + T cells were also associated with higher postinfection expression of lipopolysaccharide binding protein, a microbial translocation marker, suggestive of more extensive gut damage. CD4 + T cells expressing α 4 β 7 were rapidly depleted very early in HIV infection, particularly from the GI mucosa, and were not restored by early antiretroviral therapy. This study provides a link between α 4 β 7 expression and HIV clinical outcomes in humans, in line with observations made in NHPs. Given the availability of a clinically approved anti-α 4 β 7 monoclonal antibody for treatment of inflammatory bowel disease, these data support further evaluation of targeting α 4 β 7 integrin as a clinical intervention during HIV infection., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Universal access to highly active antiretroviral therapy (HAART) is still elusive in most developing nations. We asked whether peer support influenced adherence and treatment outcome and if a single viral load (VL) could define treatment failure in a resource-limited setting., Methods: A multicenter longitudinal and cross-sectional survey of VL, CD4 T cells, and adherence in 546 patients receiving HAART for up to 228 months. VL and CD4 counts were determined using m2000 Abbott RealTime HIV-1 assay and FACS counters, respectively. Adherence was assessed based on pill count and on self-report., Results: Of the patients, 55.8%, 22.2%, and 22% had good, fair, and poor adherence, respectively. Adherence, peer support, and regimen, but not HIV disclosure, age, or gender, independently correlated with VL and durability of treatment in a multivariate analysis (P < 0.001). Treatment failure was 35.9% using sequential VL but ranged between 27% and 35% using alternate single VL cross-sectional definitions. More patients failed stavudine (41.2%) than zidovudine (37.4%) or tenofovir (28.8%, P = 0.043) treatment arms. Peer support correlated positively with adherence (χ(2), P < 0.001), with nonadherence being highest in the stavudine arm. VL before the time of regimen switch was comparable between patients switching and not switching treatment. Moreover, 36% of those switching still failed the second-line regimen., Conclusion: Weak adherence support and inaccessible VL testing threaten to compromise the success of HAART scale-up in Kenya. To hasten antiretroviral therapy monitoring and decision making, we suggest strengthening patient-focused adherence programs, optimizing and aligning regimen to WHO standards, and a single point-of-care VL testing when multiple tests are unavailable.