Cervical cancer prevention and control in women living with human immunodeficiency virus.

Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem.

AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood-brain barrier pericytes.

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance.

Cyclophilin A facilitates HIV-1 integration.

Cyclophilin A (CypA) binds to the HIV-1 capsid to facilitate reverse transcription and nuclear entry and counter the antiviral activity of TRIM5α. Interestingly, recent studies suggest that the capsid enters the nucleus of an infected cell and uncoats prior to integration. We have previously reported that the capsid protein regulates HIV-1 integration. Therefore, we probed whether CypA-capsid interaction also regulates this post-nuclear entry step. First, we challenged CypA-expressing (CypA+/+) and CypA-depleted (CypA-/-) cells with HIV-1 and quantified the levels of provirus. CypA-depletion significantly reduced integration, an effect that was independent of CypA's effect on reverse transcription, nuclear entry, and the presence or absence of TRIM5α. In addition, cyclosporin A, an inhibitor that disrupts CypA-capsid binding, inhibited proviral integration in CypA+/+ cells but not in CypA-/- cells. HIV-1 capsid mutants (G89V and P90A) deficient in CypA binding were also blocked at the integration step in CypA+/+ cells but not in CypA-/- cells. Then, to understand the mechanism, we assessed the integration activity of the HIV-1 preintegration complexes (PICs) extracted from acutely infected cells. PICs from CypA-/- cells retained lower integration activity in vitro compared to those from CypA+/+ cells. PICs from cells depleted of both CypA and TRIM5α also had lower activity, suggesting that CypA's effect on PIC was independent of TRIM5α. Finally, CypA protein specifically stimulated PIC activity, as this effect was significantly blocked by CsA. Collectively, these results provide strong evidence that CypA directly promotes HIV-1 integration, a previously unknown role of this host factor in the nucleus of an infected cell. IMPORTANCE: Interaction between the HIV-1 capsid and host cellular factors is essential for infection. However, the molecular details and functional consequences of viral-host factor interactions during HIV-1 infection are not fully understood. Over 30 years ago, Cyclophilin A (CypA) was identified as the first host protein to bind to the HIV-1 capsid. Now it is established that CypA-capsid interaction promotes reverse transcription and nuclear entry of HIV-1. In addition, CypA blocks TRIM5α-mediated restriction of HIV-1. In this report, we show that CypA promotes the post-nuclear entry step of HIV-1 integration by binding to the viral capsid. Notably, we show that CypA stimulates the viral DNA integration activity of the HIV-1 preintegration complex. Collectively, our studies identify a novel role of CypA during the early steps of HIV-1 infection. This new knowledge is important because recent reports suggest that an operationally intact HIV-1 capsid enters the nucleus of an infected cell.

Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies.

The hydrophobic pocket found in the N-heptad repeat (NHR) region of HIV-1 gp41 is a highly conserved epitope that is the target of various HIV-1-neutralizing monoclonal antibodies. Although the high conservation of the pocket makes it an attractive vaccine candidate, it has been challenging to elicit potent anti-NHR antibodies via immunization. Here, we solved a high-resolution structure of the NHR mimetic IQN17, and, consistent with previous ligand-bound gp41 pocket structures, we observed remarkable conformational plasticity of the pocket. The high malleability of this pocket led us to test whether we could improve the immunogenicity of the gp41 pocket by stabilizing its conformation. We show that the addition of five amino acids at the C terminus of IQN17, to generate IQN22, introduces a stabilizing salt bridge at the base of the peptide that rigidifies the pocket. Mice immunized with IQN22 elicited higher avidity antibodies against the gp41 pocket and a more potent, albeit still weak, neutralizing response against HIV-1 compared with IQN17. Stabilized epitope-focused immunogens could serve as the basis for future HIV-1 fusion-inhibiting vaccines.

Adaptation of Chagas Disease Screening Recommendations for a Community of At-risk HIV in the United States.

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population.

Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.

The HIV-1 genome encodes a small number of proteins with structural, enzymatic, regulatory, and accessory functions. These viral proteins interact with a number of host factors to promote the early and late stages of HIV-1 infection. During the early stages of infection, interactions between the viral proteins and host factors enable HIV-1 to enter the target cell, traverse the cytosol, dock at the nuclear pore, gain access to the nucleus, and integrate into the host genome. Similarly, the viral proteins recruit another set of host factors during the late stages of infection to orchestrate HIV-1 transcription, translation, assembly, and release of progeny virions. Among the host factors implicated in HIV-1 infection, Cyclophilin A (CypA) was identified as the first host factor to be packaged within HIV-1 particles. It is now well established that CypA promotes HIV-1 infection by directly binding to the viral capsid. Mechanistic models to pinpoint CypA's role have spanned from an effect in the producer cell to the early steps of infection in the target cell. In this review, we will describe our understanding of the role(s) of CypA in HIV-1 infection, highlight the current knowledge gaps, and discuss the potential role of this host factor in the post-nuclear entry steps of HIV-1 infection.

Rate of response to initial antiretroviral therapy according to level of pre-existing HIV-1 drug resistance detected by next-generation sequencing in the strategic timing of antiretroviral treatment (START) study.

OBJECTIVES: The main objective of this analysis was to evaluate the impact of pre-existing drug resistance by next-generation sequencing (NGS) on the risk of treatment failure (TF) of first-line regimens in participants enrolled in the START study. METHODS: Stored plasma from participants with entry HIV RNA >1000 copies/mL were analysed using NGS (llumina MiSeq). Pre-existing drug resistance was defined using the mutations considered by the Stanford HIV Drug Resistance Database (HIVDB v8.6) to calculate the genotypic susceptibility score (GSS, estimating the number of active drugs) for the first-line regimen at the detection threshold windows of >20%, >5%, and >2% of the viral population. Survival analysis was conducted to evaluate the association between the GSS and risk of TF (viral load >200 copies/mL plus treatment change). RESULTS: Baseline NGS data were available for 1380 antiretroviral therapy (ART)-naïve participants enrolled over 2009-2013. First-line ART included a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 976 (71%), a boosted protease inhibitor in 297 (22%), or an integrase strand transfer inhibitor in 107 (8%). The proportions of participants with GSS <3 were 7% for >20%, 10% for >5%, and 17% for the >2% thresholds, respectively. The adjusted hazard ratio of TF associated with a GSS of 0-2.75 versus 3 in the subset of participants with mutations detected at the >2% threshold was 1.66 (95% confidence interval 1.01-2.74; p = 0.05) and 2.32 (95% confidence interval 1.32-4.09; p = 0.003) after restricting the analysis to participants who started an NNRTI-based regimen. CONCLUSIONS: Up to 17% of participants initiated ART with a GSS <3 on the basis of NGS data. Minority variants were predictive of TF, especially for participants starting NNRTI-based regimens.

Prevalence of genital high-risk human papillomavirus infections and associated factors among women living with human immunodeficiency virus in Uganda.

BACKGROUND: Women living with HIV are at risk for cervical dysplasia and cancer worldwide. In 2015, the World Health Organization (WHO) recommended that testing for high-risk HPV (hrHPV) infection be incorporated into cervical cancer screening programs using molecular nucleic acid tests (NATs) but this has not previously been done in Uganda. The country's coverage for Human Papilloma Virus (HPV) screening remains low at less than 10% for women aged 25-49 years. This study determined the genital prevalence of hrHPV infection and the associated factors among women living with HIV in Uganda. METHODS: A descriptive cross-sectional study was conducted in 15 selected health facilities among participants who were on Antiretroviral therapy (ART). Participants who consented to participate were instructed on how to collect their own high vaginal swabs using a cervical brush for HPV molecular testing (HPV DNA or HPV RNA) and their demographics data was collected using a standard questionnaire. Laboratory diagnosis for HPV molecular testing was done using Gene xpert machines and Hologic Aptima Machine. Modified Poisson regression analysis was conducted to determine the associated factors. RESULTS: This study involved 5856 HIV positive participants on ART. A total of 2006 out of 5856 (34.3%) participants had high risk HPV infections. HPV infections by genotypes were: HPV16 317(15.8%), HPV 18/45 308 (15.4%) and other high-risk HPV 1381 (68.8%). The independent factors associated with all hrHPV were parity, education level, having more than one partner, and engaging in early sex. Smoking was associated with HPV 16, HPV 18/45 and other hrHPV. Age was associated with all hrHPV, marital status with HPV 16, and occupation with HPV 16. CONCLUSIONS: The prevalence of genital high-risk HPV infections among HIV positive women attending ART clinics in public facilities in Uganda was high. Other hrHPV genotype was the commonest compared to 18/45 and HPV 16. The integration of cervical cancer screening in ART programmes remains paramount to support the early detection of cervical cancer and Non-invasive self-collected urine and vaginal sampling for cervical cancer screening present an opportunity.

Optimal STI controls for HIV patients based on an efficient deep Q learning method.

We investigate an efficient computational tool to suggest useful treatment regimens for people infected with the human immunodeficiency virus (HIV). Structured treatment interruption (STI) is a regimen in which therapeutic drugs are periodically administered and withdrawn to give patients relief from an arduous drug therapy. Numerous studies have been conducted to find better STI treatment strategies using various computational tools with mathematical models of HIV infection. In this paper, we leverage a modified version of the double deep Q network with prioritized experience replay to improve the performance of classic deep learning algorithms. Numerical simulation results show that our methodology produces significantly more optimal cost values for shorter treatment periods compared to other recent studies. Furthermore, our proposed algorithm performs well in one-day segment scenarios, whereas previous studies only reported results for five-day segment scenarios.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry.

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.

Compliance to Viral Load Monitoring Schedules Among Women Attending Prevention of Vertical HIV Transmission Services Before and During the COVID-19 Pandemic in Ehlanzeni District, Mpumalanga, South Africa.

Human immunodeficiency virus (HIV) viral load (VL) monitoring was likely interrupted during the Coronavirus disease 2019 (COVID-19) pandemic. We used routine data on repeat VL testing among 667 prevention of vertical HIV transmission (PVT) clients in Ehlanzeni district, to determine compliance to VL testing recommendations and associated factors during different time periods: pre-COVID-19, transition, and COVID-19. Descriptive and multivariable Poisson regression analyses were conducted, with and without including revised PVT-guidelines rolled out in January-2020. Among 405 women with ≥ 2 VL tests, the overall median age was 30 years (interquartile range: 26-35 years). Compliance to recommended VL testing guidelines ranged between 81.5% (172/211) and 92.3% (191/207) at different time periods. Across all three periods and when revised PVT-guidelines were used, being compliant was significantly reduced among those with earliest VL = 50-999 copies/ml (incidence rate ratio (IRR) = 0.71 [95% confidence interval (CI) 0.61-0.82], p value < 0.001) and VL ≥ 1000 copies/ml (IRR = 0.18 [95% CI 0.09-0.36], p value < 0.001). When guideline revisions were excluded, compliance was only significantly reduced among those with VL ≥ 1000 copies/ml (IRR = 0.14 [95% CI 0.06-0.32], p value < 0.001) and increased during the COVID-19 period versus pre-COVID-19 (IRR = 1.10 [95% CI 1.05-1.15], p value < 0.001). Similar significant associations between compliance and VL level were observed when the COVID-19 period was analyzed separately. Significantly increased compliance to VL testing among the 25-34 years age-group versus younger women was also observed across all periods. These results highlight the importance of strengthening strategies such as short message service reminders and educational messaging, reaching all age-groups, to fast-track implementation targets for VL monitoring.

The Impact of COVID-19 on the HIV Cascade of Care in Botswana - An Interrupted Time Series.

Globally, Botswana has one of the highest burdens of HIV. This study estimated the impact of the COVID-19 pandemic on the HIV cascade of care in Sub-Saharan Africa. We conducted an interrupted time series analysis on national-level data to estimate the effect of COVID-19 on the numbers of HIV tests, positive HIV tests and ART initiations from April 2019 until March 2021. In multivariable Poisson interrupted time series regression, the COVID-19 lockdown was associated with a 27% decrease in the monthly numbers of HIV tests (IRR 0.73, 95%CI 0.72-0.73), a 25% decrease in HIV positive tests (IRR 0.75, 95%CI 0.71-0.79), and a 43% reduction in ART initiations (IRR 0.57, 95%CI 0.55-0.60). The impact of the pandemic on all three outcomes was worse in males and those aged ≥ 50 years. In conclusion, COVID-19 had a strong negative impact on HIV screening, diagnosis and ART initiation in Botswana.

Epidemiological changes and outcomes of people living with HIV admitted to the intensive care unit: a 14-year retrospective study.

PURPOSES: Since 2016, the World Health Organization has recommended universal antiretroviral therapy (ART) for all people living with Human Immunodeficiency Virus (PLHIV). This recommendation may have influenced the characteristics and outcomes of PLHIV admitted to the Intensive Care Unit (ICU). This study aims to identify changes in the epidemiological and clinical characteristics of PLHIV admitted to the ICU, and their short- and medium-term outcomes before and after the implementation of universal ART (periods 2006-2015 and 2016-2019). METHODS: This retrospective, observational, single-center study included all adult PLHIV admitted to the ICU of a University Hospital in Barcelona from 2006 to 2019. RESULTS: The study included 502 admissions involving 428 patients, predominantly men (75%) with a median (P25-P75) age of 47.5 years (39.7-53.9). Ninety-one percent were diagnosed with HIV before admission, with 82% under ART and 60% admitted from the emergency department. In 2016-2019, there were more patients on ART pre-admission, reduced needs for invasive mechanical ventilation (IMV) and fewer in-ICU complications. ICU mortality was also lower (14% vs 7%). Predictors of in-ICU mortality included acquired immunodeficiency syndrome defining event (ADE)-related admissions, ICU complications, higher SOFA scores, IMV and renal replacement therapy (RRT) requirement. ART use during ICU admission was protective. Higher SOFA scores, admission from hospital wards, and more comorbidities predicted one-year mortality. CONCLUSIONS: The in-ICU mortality of critically ill PLHIV has decreased in recent years, likely due to changes in patient characteristics. Pre- and ICU admission features remain the primary predictors of short- and medium-term outcomes.

Is doxycycline post-exposure prophylaxis being utilised in Germany? Insights from an online survey among German men who have sex with men.

PURPOSE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.

Structural and computational studies of HIV-1 RNA.

Viruses remain a global threat to animals, plants, and humans. The type 1 human immunodeficiency virus (HIV-1) is a member of the retrovirus family and carries an RNA genome, which is reverse transcribed into viral DNA and further integrated into the host-cell DNA for viral replication and proliferation. The RNA structures from the HIV-1 genome provide valuable insights into the mechanisms underlying the viral replication cycle. Moreover, these structures serve as models for designing novel therapeutic approaches. Here, we review structural data on RNA from the HIV-1 genome as well as computational studies based on these structural data. The review is organized according to the type of structured RNA element which contributes to different steps in the viral replication cycle. This is followed by an overview of the HIV-1 transactivation response element (TAR) RNA as a model system for understanding dynamics and interactions in the viral RNA systems. The review concludes with a description of computational studies, highlighting the impact of biomolecular simulations in elucidating the mechanistic details of various steps in the HIV-1's replication cycle.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Expression profiling & functional characterization of candidate miRNAs in serum exosomes among Indians with & without HIV-tuberculosis coinfection.

Background & objectives Despite the evidence of population differences in miRNA expression, limited information is available about the expression profile of miRNAs in Indian tuberculosis (TB) patients. The present study aimed to investigate the expression profile of candidate serum exosomal microRNAs in Indian patients with and without HIV-TB coinfection. Methods The pool samples of serum exosomes of study participants (HIV-TB coinfection, extra-pulmonary TB, HIV mono-infection, pulmonary TB) and healthy humans were processed for the isolation of total RNA followed by miRNA analysis using miRCURY LNA human focus PCR panel by real-time PCR. The significantly altered miRNAs were identified using differential expression analysis. The target genes prediction and potential functional analysis of exclusively differentially expressed miRNAs were performed using bioinformatics tools. Results The expression profile of 57, 58, 49 and 11 miRNAs was significantly altered in exosome samples of HIV-TB coinfected, extra-pulmonary TB, HIV mono-infected and pulmonary TB patients compared to healthy controls, respectively. The set of three (hsa-let-7i-5p, hsa-miR-24-3p, hsa-miR-92a-3p), three (hsa-miR-20a-5p, hsa-let-7e-5p, hsa-miR-26a-5p) and four (hsa-miR-21-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-146a-5p) miRNAs were exclusively significantly differentially expressed in study participants with HIV-TB coinfection, extra-pulmonary TB and pulmonary TB, respectively. Most of the target genes of exclusively differentially expressed miRNAs were enriched in pathways in cancer, MAPK signalling pathway and Ras signalling pathway. Interpretation & conclusions The present study demonstrates a distinct expression profile of miRNAs in serum exosomes of the study participants and identified crucial miRNAs which may have a significant impact on the biomarker analysis and pathogenesis of TB in Indian patients.

Enhancing indicator condition-guided HIV testing in Taiwan: a nationwide case-control study from 2009 to 2015.

BACKGROUND: Although indicator condition (IC)-guided HIV testing (IC-HIVT) is effective at facilitating timely HIV diagnosis, research on IC categories and the related HIV risk in Taiwan is limited. To improve the adoption and spread of IC-HIVT in Taiwan, this study compared the IC categories of people living with HIV (PLWH) and non-HIV controls and investigated delays in the diagnosis of HIV infection. METHODS: This nationwide, retrospective, 1:10-matched case-control study analyzed data from the Notifiable Diseases Surveillance System and National Health Insurance Research Database to evaluate 42 ICs for the 5-year period preceding a matched HIV diagnostic date from 2009 to 2015. The ICs were divided into category 1 ICs (AIDS-defining opportunistic illnesses [AOIs]), category 2 ICs (diseases associated with impaired immunity or malignancy but not AOIs), category 3 ICs (ICs associated with sexual behaviors), and category 4 ICs (mononucleosis or mononucleosis-like syndrome). Logistic regression was used to evaluate the HIV risk associated with each IC category (at the overall and annual levels) before the index date. Wilcoxon rank-sum test was performed to assess changes in diagnostic delays following an incident IC category by HIV transmission routes. RESULTS: Fourteen thousand three hundred forty-seven PLWH were matched with 143,470 non-HIV controls. The prevalence results for all ICs and category 1-4 ICs were, respectively, 42.59%, 11.16%, 15.68%, 26.48%, and 0.97% among PLWH and 8.73%, 1.05%, 4.53%, 3.69%, and 0.02% among non-HIV controls (all P < 0.001). Each IC category posed a significantly higher risk of HIV infection overall and annually. The median (interquartile range) potential delay in HIV diagnosis was 15 (7-44), 324.5 (36-947), 234 (13-976), and 74 (33-476) days for category 1-4 ICs, respectively. Except for category 1 for men who have sex with men, these values remained stable across 2009-2015, regardless of the HIV transmission route. CONCLUSIONS: Given the ongoing HIV diagnostic delay, IC-HIVT should be upgraded and adapted to each IC category to enhance early HIV diagnosis.