Potent Antiretroviral Therapy Research Articles

Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

SARS-CoV-2 mRNA Vaccines Induce Greater Complement Activation and Decreased Viremia and Nef Antibodies in Men With HIV-1.

Immune dysregulation in people with human immunodeficiency virus-1 (PWH) persists despite potent antiretroviral therapy and, consequently, PWH tend to have lower immune responses to licensed vaccines. However, limited information is available about the impact of mRNA vaccines in PWH. This study details the immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in PWH and their impact on HIV-1. We quantified anti-S immunoglobulin G (IgG) binding and neutralization of 3 SARS-CoV-2 variants of concern and complement activation in blood from virally suppressed men with HIV-1 (MWH) and men without HIV-1 (MWOH), and the characteristics that may impact the vaccine immune responses. We also studied antibody levels against HIV-1 proteins and HIV-1 plasma RNA. MWH had lower anti-S IgG binding and neutralizing antibodies against the 3 variants compared to MWOH. MWH also produced anti-S1 antibodies with a 10-fold greater ability to activate complement and exhibited higher C3a blood levels than MWOH. MWH had decreased residual HIV-1 plasma viremia and anti-Nef IgG approximately 100 days after immunization. MWH respond to SARS-CoV-2 mRNA vaccines with lower antibody titers and with greater activation of complement, while exhibiting a decrease in HIV-1 viremia and anti-Nef antibodies. These results suggest an important role of complement activation mediating protection in MWH.

Advances in HIV therapeutics and cure strategies: findings obtained through non-human primate studies.

Human immunodeficiency virus (HIV), the main contributor of the ongoing AIDS epidemic, remains one of the most challenging and complex viruses to target and eradicate due to frequent genome mutation and immune evasion. Despite the development of potent antiretroviral therapies, HIV remains an incurable infection as the virus persists in latent reservoirs throughout the body. To innovate a safe and effective cure strategy for HIV in humans, animal models are needed to better understand viral proliferation, disease progression, and therapeutic response. Nonhuman primates infected with simian immunodeficiency virus (SIV) provide an ideal model to study HIV infection and pathogenesis as they are closely related to humans genetically and express phenotypically similar immune systems. Examining the clinical outcomes of novel treatment strategies within nonhuman primates facilitates our understanding of HIV latency and advances the development of a true cure to HIV.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018

Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Antigen Presenting Cell-Mediated HIV-1 Trans Infection in the Establishment and Maintenance of the Viral Reservoir

Despite potent antiretroviral therapy (ART), an HIV-1 reservoir persists that represents a major barrier to a cure. Understanding the mechanisms by which the HIV-1 reservoir is established and maintained is critical for the discovery of effective treatments to significantly reduce or eliminate the viral reservoir. In addition to cis infection, in which HIV-1 directly infects target CD4+ T cells, cell-to-cell transmission, or trans infection, can also occur. HIV-1 trans infection is significantly more efficient than cis infection, mostly due to the occurrence of multiple infections per cell during transfer. Additionally, trans infection is efficient even in the presence of ART and/or neutralizing antibodies. Cell-to-cell transmission is mediated by CD4+ T cells and professional antigen presenting cells (APC). Here we focus on APC, i.e., myeloid dendritic cells, B lymphocytes, and monocytes/macrophages, that bind, internalize, and transfer HIV-1 to target CD4+ T cells via various proposed mechanisms. We assess the potential impact of trans infection on the establishment and maintenance of the HIV-1 reservoir including its role in disease progression. We consider the natural interactions between APC and CD4+ T cells in vivo that HIV-1 may hijack, allowing for the highly efficient trans infection of CD4+ T cells, maintaining the viral reservoirs in tissue despite undetectable plasma viral loads in peripheral blood. We propose that these modes of viral pathogenesis need to be addressed in potential cure strategies to ensure eradication of the viral reservoir.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008–2018

Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Dawn of a new beginning- First renal transplant in patient with HIV in Nepal

Human immunodeficiency virus infection was traditionally considered an absolute contraindication for transplantation because of the concern that immunosuppression would accelerate HIV disease progression, resulting in increased mortality and a "waste" of organs. Since potent antiretroviral therapy became widely available in 1996, the prognosis of patients with HIV infection has dramatically improved. HIV-infected patients are now accepted recipients of both HIV-infected and HIV- uninfected donor organs in specialized transplant centers worldwide. However, due to stigma about the disease and lack of appropriate expertise, renal transplant in HIV patients has not been done in Nepal. Here, we report the first case of renal transplantation done in patient with HIV in Nepal. So, even in a resource limited setting like Nepal, HIV-positive ESRD patients with stable disease should be given the benefit of kidney transplantation as patient and graft survival are reasonably good with better quality of life.

The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis.

Purpose of reviewThis review explores mechanisms by which gut-derived bacterial lipopolysaccharide (LPS) and oxidized phospholipids contribute to chronic systemic inflammation and atherosclerosis.Recent findingsGut-derived LPS enters through the small intestine via two distinct pathways that involve high density lipoproteins (HDL) and chylomicrons. Gut-derived LPS can bind to the LPS-binding protein (LBP) and to HDL3 in the small intestine and travel through the portal vein to the liver where it does not elicit an inflammatory reaction, and is inactivated or it can bind to HDL2 and travel through the portal vein to the liver where it elicits an inflammatory reaction. Alternatively, in the small intestine, LPS can bind to LBP and chylomicrons and travel through the lymphatics to the systemic circulation and enhance inflammatory processes including atherosclerosis. Oxidized phospholipids formed in the small intestine regulate the levels and uptake of LPS in small intestine by regulating antimicrobial proteins such as intestinal alkaline phosphatase. Gut-derived LPS and oxidized phospholipids may be responsible for the persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels.SummaryBy targeting gut-derived oxidized phospholipids, the uptake of gut-derived LPS may be reduced to decrease systemic inflammation and atherosclerosis.

Life expectancy of people with HIV on long-term antiretroviral therapy in Europe and North America: a cohort study

BackgroundThe life expectancy of people with HIV starting combination antiretroviral therapy (ART) has increased substantially over the past 25 years. However, individuals treated before 1996 or with less effective and more toxic regimens than those currently available might have a worse prognosis. We estimated life expectancy from 2015 onwards, comparing people with HIV who started ART in different time periods since 1996. MethodsData were derived from 20 European and North American cohorts (Antiretroviral Therapy Cohort Collaboration and UK Collaborative HIV Cohort Study), for people with HIV who started potent ART after 1996 and were still on ART in 2015, or who started ART after 2015 and survived for at least 1 year. Follow-up started on or after Jan 1, 2015. Associations between mortality and demographic characteristics and biomarkers (CD4 and CD8 count in cells per μL and HIV-1 RNA viral load) at follow-up start were estimated using multivariable Poisson models. Estimated mortality rates in 5-year age bands were entered into life tables that contain follow-up information to estimate expected remaining life expectancy, stratified by sex and variables associated with mortality, and standardised to the proportion of people with HIV in each stratum. Life expectancy was compared with the French general population, as more data were available for France than for other countries included in the analyses. FindingsOf the 206 891 people with HIV eligible for inclusion from the cohort data, 5780 died during 619 356 person-years of follow-up after 2015. For women, the standardised remaining years of life expectancy at age 40 years for individuals starting ART between 1996 and 2014 was 36·0 years (95% CI 35·4–36·6), whereas it was 39·4 years (39·0–39·8) for individuals starting after 2015 (general population comparator 46·0 years). Corresponding figures for men were 34·7 years (34·1–35·3) and 37·2 years (36·6–38·8), respectively (general population comparator 40·3 years). For women starting ART between 1996 and 2014, with a CD4 count of 0–49 cells per μL at the commencement of follow-up, remaining life expectancy at age 40 years was 19·4 years (95% CI 18·2–20·6), rising to 40·4 years (40·0–40·8) for people with a CD4 count of 500 cells per μL or greater at commencement of follow-up. Corresponding figures for women starting ART after 2015 were 24·9 years (23·9–25·9) and 42·6 years (422–43·0), respectively. For men starting ART between 1996 and 2014 with a CD4 count of 0–49 cells per μL at commencement of follow-up, remaining life expectancy at age 40 years was 18·2 years (17·0–19·4), rising to 38·2 years (37·6–38·8) for men with a CD4 count of 500 cells per μL or more at commencement of follow-up. Corresponding remaining life expectancy for men starting ART after 2015 was 23·7 years (22·7–24·7) and 39·5 years (38·9–40·1), respectively. InterpretationFor people with HIV on long-term ART with high CD4 cell counts, life expectancies are estimated to be close to those of the general population, regardless of when they started ART. However, for people with HIV with low CD4 cell counts, estimates of remaining life expectancy are up to 30 years lower than in the general population, indicating the importance of early diagnosis and sustained treatment. FundingUS National Institute on Alcohol Abuse and Alcoholism, UK Medical Research Council.

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.

ApoA-I mimetics reduce systemic and gut inflammation in chronic treated HIV.

Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mimetic peptides 6F and 4F attenuate systemic and gut inflammation in chronic HIV. We used two humanized murine models of HIV infection and gut explants from 10 uninfected and 10 HIV infected persons on potent ART, to determine the in vivo and ex vivo impact of apoA-I mimetics on systemic and intestinal inflammation in HIV. When compared to HIV infected humanized mice treated with ART alone, mice on oral apoA-I mimetic peptide 6F with ART had consistently reduced plasma and gut tissue cytokines (TNF-α, IL-6) and chemokines (CX3CL1) that are products of ADAM17 sheddase activity. Oral 6F attenuated gut protein levels of ADAM17 that were increased in HIV-1 infected mice on potent ART compared to uninfected mice. Adding oxidized lipoproteins and endotoxin (LPS) ex vivo to gut explants from HIV infected persons increased levels of ADAM17 in myeloid and intestinal cells, which increased TNF-α and CX3CL1. Both 4F and 6F attenuated these changes. Our preclinical data suggest that apoA-I mimetic peptides provide a novel therapeutic strategy that can target increased protein levels of ADAM17 and its sheddase activity that contribute to intestinal and systemic inflammation in treated HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target.

Latency Reversal and Clearance of Persistent HIV Infection.

Efforts to prevent and treat human immunodeficiency virus type 1 (HIV) infection have begun to blunt the spread of HIV infection. Potent, safe, and well-tolerated antiretroviral therapy (ART) allows those infected with HIV to attain a life expectancy similar to that of HIV-uninfected individuals. But the persistence of the quiescent retroviral genome, enforced by the natural proliferative responses of the immune system itself, and a delicate balance of regulators viral expression, mandates lifelong ART suppression to prevent rebound viremia and the return of disease.The approach to HIV eradication that has been studied the most extensively envisions adding therapies to induce the expression of quiescent HIV-1 genomes following the control of viremia by ART, paired with immunotherapies to clear persistent infection. Paired testing of latency reversal and clearance strategies has begun, but the field is still in its infancy and additional obstacles to HIV eradication may emerge. However, there is reason for optimism that together with advances in ART delivery and HIV prevention strategies, efforts in HIV cure research will markedly diminish the effect of the HIV pandemic on society.

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques.

The ongoing COVID-19 vaccine rollout is critical for reducing SARS-CoV-2 infections, hospitalizations, and deaths worldwide. Unfortunately, massive disparities exist in getting vaccines to vulnerable populations, including people living with HIV. Preliminary studies indicate that COVID-19 mRNA vaccines are safe and immunogenic in people living with HIV that are virally suppressed with potent antiretroviral therapy but may be less efficacious in immunocompromised individuals. This raises the concern that COVID-19 vaccines may be less effective in resource poor settings with limited access to antiretroviral therapy. Here, we evaluated the immunogenicity of a single dose COVID-19 replicon RNA vaccine expressing Spike protein (A.1) from SARS-CoV-2 (repRNA-CoV2S) in immunocompromised, SIV infected and immune competent, naïve pigtail macaques. Moderate vaccine-specific cellular Th1 T-cell responses and binding and neutralizing antibodies were induced by repRNA-CoV2S in SIV infected animals and naïve animals. Furthermore, vaccine immunogenicity was elicited even among the animals with the highest SIV viral burden or lowest peripheral CD4 counts prior to immunization. This study provides evidence that a SARS-CoV-2 repRNA vaccine could be employed to induce strong immunity against COVID-19 in HIV infected and other immunocompromised individuals.

117. Trends in Four-class HIV Drug Resistance in Treatment-experienced Patients in the United States

BackgroundDespite the availability of potent antiretroviral therapy, only 56% of people living with HIV in the US were virally suppressed in 2018. Drug resistance can hinder suppression, especially among treatment-experienced patients, in whom the prevalence of 4-class drug resistance (4CR) is unknown.MethodsGenotypic results of PhenoSense GT® Plus Integrase (Monogram Biosciences, South San Francisco, CA) obtained from Apr 2014 to Dec 2020 were used to assign susceptibility to nucleos(t)ide reverse transcriptase, non-nucleoside reverse transcriptase, integrase, and protease inhibitors (NRTIs, NNRTI, INIs, and PIs). Data were analyzed using summary statistics, 2 proportion Z test, one-way ANOVA and Tukey-Kramer; p < 0.05 was significant.ResultsAmong 13,651 patients with 15,372 tests, median age was 43 years; most had HIV-1 subtype B infection (95.09%), followed by AG (1.32%).Among 12,303 patients with only one test, 4CR prevalence was 1.55%. Among 1,348 patients with more than one test, 4CR was seen in 3.64% of patients, and in 4.60% if cumulative resistance reports were assembled for each patient. Patients with 4CR were significantly older than those with less resistance.The incidence of 4CR fluctuated, with a decline from 2.61% of patients tested in 2014 to 1.38% in 2017, an increase to 2.36% in 2018, and a decline to 1.56% in 2020. Among patients with more than one test, 21.01% gained resistance to a drug in a new class over an average of 19.5 months.Most new resistance each year was to NNRTIs, followed by NRTIs, INIs, and PIs. The incidence of PI resistance declined for PIs from 13.34% of patients tested in 2014 to 11.82% in 2020, but increased for INIs from 14.56% in 2014 to 16.49% in 2020. The regimen expected to be suppressive in the greatest proportion of patients was dolutegravir + darunavir/cobicistat (94.51%).ConclusionThe prevalence of 4CR has declined over time, but remains clinically relevant, particularly in older patients who may struggle with adherence due to complex regimens, comorbidities and polypharmacy. New drug classes may benefit this group. The concurrent increase in INI and decline in PI resistance may reflect changes in prescribing practices. Drug resistance may be underestimated unless cumulative resistance is determined.Disclosures Dusica Curanovic, PhD, Monogram Biosciences (Employee) Johnny Lai, BS, Monogram Biosciences (Employee, Shareholder) Christos J. Petropoulos, PhD, Monogram Biosciences (Employee, Shareholder) Charles M. Walworth, MD, Monogram Biosciences (Employee, Shareholder)

A retrospective study of distribution of HIV associated malignancies among inpatients from 2007 to 2020 in China

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population.

Decreasing Incidence and Determinants of Bacterial Pneumonia in People With HIV: The Swiss HIV Cohort Study.

Bacterial pneumonia is a leading reason for hospitalization among people with HIV (PWH); however, evidence regarding its drivers in the era of potent antiretroviral therapy is limited. We assessed risk factors for bacterial pneumonia in the Swiss HIV Cohort Study using marginal models. We further assessed the relationship between risk factors and changes in bacterial pneumonia incidence using mediation analysis. We included 12927 PWH with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100779 person-years. Bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 person-years in 2008 to 6.8 cases/1000 person-years in 2018. Older age, lower education level, intravenous drug use, smoking, lower CD4-cell count, higher HIV load, and prior pneumonia were significantly associated with higher bacterial pneumonia incidence. Notably, CD4 cell counts 350-499 cells/μL were significantly associated with an increased risk compared to CD4 ≥ 500 cells/µL (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.89). Decreasing incidence over the last decade can be explained by increased CD4-cell counts and viral suppression and decreased smoking frequency. Improvements in cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.

Web-Based Behavioral Intervention Utilizing Narrative Persuasion for HIV Prevention Among Chinese Men Who Have Sex With Men (HeHe Talks Project): Intervention Development.

BackgroundIn the era of potent antiretroviral therapy, a high level of condomless anal intercourse continues to drive increases in HIV incidence in recent years among men who have sex with men. Effective behavior change strategies for promoting HIV-preventive behaviors are warranted. Narrative persuasion is a novel health communication approach that has demonstrated its persuasive advantages in overcoming resistance to counterattitudinal messages. The efficacy of narrative persuasion in promoting health behavior changes has been well documented, but critical research gaps exist for its application to HIV prevention.ObjectiveIn this study, we aimed to (1) capitalize on narrative persuasion to design a web-based multisession intervention for reducing condomless anal intercourse among men who have sex with men in Hong Kong (the HeHe Talks Project) by following a systematic development process; and (2) describe the main components of the narrative intervention that potentially determine its persuasiveness.MethodsPersuasive themes and subtopics related to reducing condomless anal intercourse were initially proposed based on epidemiological evidence. The biographic narrative interview method was used to elicit firsthand experiential stories from a maximum variation sample of local men who have sex with men with diverse backgrounds and experiences related to HIV prevention; different types of role models were established accordingly. Framework analysis was used to aggregate the original quotations from narrators into collective narratives under 6 intervention themes. A dedicated website was finally developed for intervention delivery.ResultsA series of video-based intervention messages in biographic narrative format (firsthand experiential stories shared by men who have sex with men) combined with topic-equivalent argumentative messages were produced and programmed into 6 intervention sessions. The 6-week intervention program can be automatically delivered and monitored online.ConclusionsWe systematically created a web-based HIV prevention intervention derived from peer-generated stories. Strategies used to enhance the efficacy of the narrative intervention have been discussed within basic communication components. This paper describes the methods and experiences of the rigorous development of a narrative communication intervention for HIV prevention, which enables replication of the intervention in the future.

Persistent HIV-1 transcription in CD4+ T cells from ART-suppressed individuals can originate from biologically competent proviruses

HIV-1 is able to persist in the face of potent antiretroviral therapy (ART). A number of strategies are being explored to allow ART-free viral remission or viral eradication. In order to gauge the progress of these strategies, assays with which to measure viral reservoir size and activity are needed. In a large percentage of aviremic individuals on suppressive ART, viral transcripts can be detected in peripheral blood CD4+ T cells. While this cell-associated RNA has been considered as a marker of viral reservoir activity, it is unclear whether cell-associated viral transcripts in aviremic individuals originate from biologically competent proviruses as opposed to being a product of abortive transcription from defective proviruses. We assessed whether cell-associated viral RNA in peripheral blood CD4+ T cells from aviremic individuals on ART originated from biologically competent proviruses. We demonstrate that cell-associated viral RNA transcripts were highly related to viral sequences obtained by ex vivo outgrowth. This relationship was also observed when viral transcription in the outgrowth cultures was limited to donor CD4+ T cells. Our study indicates that cell-associated viral RNA warrants further consideration as a viral reservoir surrogate in individuals on suppressive ART.

P-081. Hyperaldosteronism in pregnancy: a case control study

HIV-1 is able to persist in the face of potent antiretroviral therapy (ART). A number of strategies are being explored to allow ART-free viral remission or viral eradication. In order to gauge the progress of these strategies, assays with which to measure viral reservoir size and activity are needed. In a large percentage of aviremic individuals on suppressive ART, viral transcripts can be detected in peripheral blood CD4+ T cells. While this cell-associated RNA has been considered as a marker of viral reservoir activity, it is unclear whether cell-associated viral transcripts in aviremic individuals originate from biologically competent proviruses as opposed to being a product of abortive transcription from defective proviruses. We assessed whether cell-associated viral RNA in peripheral blood CD4+ T cells from aviremic individuals on ART originated from biologically competent proviruses. We demonstrate that cell-associated viral RNA transcripts were highly related to viral sequences obtained by ex vivo outgrowth. This relationship was also observed when viral transcription in the outgrowth cultures was limited to donor CD4+ T cells. Our study indicates that cell-associated viral RNA warrants further consideration as a viral reservoir surrogate in individuals on suppressive ART.

Health care Providers' Perceptions About Overweight and Obesity Among People Living With Human Immunodeficiency Virus in Nigeria.

HIV infection was associated with significant weight loss before the advent of potent antiretroviral therapy (ART). Weight gain while on treatment was seen as a clinical indicator of treatment success. Perceptions of health care providers (HCPs) about obesity among people living with (PLHIV) were examined. We conducted 16 key informant interviews with HCPs in two states in southeastern Nigeria, which were then coded thematically. The respondents included seven physicians, four nurses, three adherence counselors, and two pharmacists. The analysis revealed three key themes: HCPs do not see excess weight gain as a problem; there are several challenges in managing obesity among PLHIV; and comorbidities play a role in the management of obesity among PLHIV. We conclude that obesity among PLHIV is an important clinical issue that HCPs need to address with the commencement of ART.