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Objective: To investigate the distribution characteristics of HIV-1 subtypes, the status of transmitted drug resistance (TDR), and the influencing factors of TDR in treatment-naive patients with AIDS who are hospitalized., Methods: Treatment-naive patients with AIDS who were admitted to the Infectious Disease Department, Public Health Clinical Center of Chengdu between January 2020 and December 2022 were enrolled in the study. The diagnosis and confirmation diagnosis of all the subjects were made at the same hospital. Blood samples were collected from the subjects before antiretroviral therapy (ART). The in-house method was used for HIV gene amplification and sequencing. A phylogenetic tree was constructed to analyze the HIV-1 subtypes. The Stanford HIV Drug Resistance Database was used to conduct an online comparative analysis of the drug resistance mutation sites and to determine the types and levels of drug resistance. The distribution characteristics of HIV-1 subtypes, the occurrence of TDR, and the influencing factors of TDR were analyzed., Results: A total of 213 patients were included in the study and their blood samples were collected. HIV-1 subtypes were successfully amplified in 83.10% (177/213) of the subjects. Ten HIV subtypes were identified, with CRF07_BC being the most common subtypes, accounting for 43.50% (77/177), which was followed by CRF01_AE at 37.85%. Unique recombinant forms (URFs) were relatively uncommon, accounting for 8.47%. The other subtypes accounted for 10.17%. These 4 categories of HIV-1 subtypes were distributed with statistically significant differences in different age groups ( P =0.024). Further analysis revealed significant differences in the distribution of the HIV-1 subtypes of CRF01_AE and URFs between the groups of patients aged 30-50 years and those over 50. In addition, URFs accounted for a higher proportion in patients aged 30 to 50 years ( P =0.008). The incidences of TDR were 6.49%, 8.96%, 13.33%, and 5.56% for CRF07_BC, CRF01_AE, URFs, and other subtypes, respectively, showing no significant difference ( P >0.05). The overall TDR was 6.57%. The TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 5.16%, and the main mutation sites were V179D/E, E138A/G, V106M/I, and Y181C. The TDR for nucleoside reverse transcriptase inhibitors (NRTIs) was 1.88%, and the main mutation site was M184V. One patient was found to be resistant to both NNRTIs and NRTIs. The highly resistant rate was 4.23%, moderate resistance was 0.47%, and low resistance was 1.88%. No significant effects of the specific years, demographic characteristics, transmission route, baseline condition, and opportunistic infections on TDR were found in this study ( P >0.05)., Conclusions: The HIV-1 subtypes are diverse and complex in treatment-naive patients with AIDS who were hospitalized. The overall prevalence of TDR is relatively high. It is necessary to strengthen HIV drug resistance testing to optimize ART treatment and reduce the risk of drug resistance transmission., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH)., Methods: In this analysis, serum samples of PLWH from the RESINA multicenter cohort were reanalyzed for TTV. Investigated clinical and epidemiological parameters included human pegivirus load, patient age and sex, HIV load, CD4+ T-cell count (Centers for Disease Control and Prevention [CDC] stage 1, 2, or 3), and CDC clinical stage (1993 CDC classification system; stage A, B, or C) before initiation of antiretroviral therapy. Regression analysis was used to detect possible associations among parameters., Results: Our analysis confirmed TTV as a strong predictor of CD4+ T-cell count and CDC class 3. This relationship was used to propose a first classification of TTV load with regard to clinical stage. We found no association with clinical CDC stages A-C. The human pegivirus load was inversely correlated with HIV load but not TTV load., Conclusions: TTV load was associated with immunodeficiency in PLWH. Neither TTV nor HIV load were predictive for the clinical categories of HIV infection., Competing Interests: Potential conflicts of interest. B. E. O. J. has received consulting fees from Gilead, ViiV Healthcare (ViiV) and Merck Sharpe and Dohme (MSD). B. E. O. J. has received payment or honoraria for lectures and presentations from Gilead, ViiV and GSK. B. E. O. J. has received support for meetings and travel from Gilead. B. E. O. J. is scientific secretary of the German AIDS Society (unpaid). S. E. has received grants or contracts, support for meetings or travel, and payments or honoraria for lectures or presentations from Gilead, ViiV, MSD and Janssen. S. E. participated on a data safety monitoring board or advisory board for Gilead, ViiV, MSD, Janssen and GSK. S. E. is in a leadership or fiduciary role for the German AIDS Society and the National AIDS Comission NRW. S. E.reveived equipment, materials, drugs, medical writing, gifts or other services from Gilead and GSK. N. L. received consulting fees from ViiV. N. L. received honoraria for lectures from ViiV and MSD. N. L. received support for travel from the Deutsche AIDS Gesellschaft. J. K. R. received consulting fees from Behringer. J. K. R. received payment for lectures or presentations from Gilead, MSD and ViiV. J. K. R. was payed for the particpation on a data safety monitoring board or advisory board for Abivax. J. K. R. is EACS (European AIDS Clinical Society) board member. C. B. received grants or contracts from DZIF (German Center for Infection Research) and DFG (German Research Foundation). C. B. received consulting fees, payment for lectures and presentations, and support for meetings or travel from Abbvie, MSD, Janssen, Gilead and ViiV. C. B. is governing board member of EACS. R. K. received grants from DZIF. R. K. received payment for presentations or lectures from Janssen, Roche, Hologic, Abbvie, Abbott, MSD, ViiV, Gilead and Pfizer. R. K. particpated on a data safety monitoring board or advisory board for ViiV, Gilead, Pfizer, MSD and Janssen. All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023. Methods: An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University's HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis. Results: A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ 2 =30.435, P <0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 + T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P <0.05).Multivariate logistic analysis showed that the baseline CD4 + T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P <0.05). Conclusion: The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 + T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

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., (© 2021. The Author(s).)

Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp 3 atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available in the supplementary material.

Acquired immunodeficiency syndrome a disease with high mortality rates is caused by the well-known human immunodeficiency virus. The disease is characterized by several opportunistic infections owing to the decreased CD4 lymphocyte counts. Oral manifestations of human immunodeficiency virus are vital as they are one of the early manifestations of the disease. Also, they serve as prognostic markers as they correlate with the CD4 lymphocyte counts of the affected individuals. Human immunodeficiency virus is not only common in the adult population but also can affect pediatric patients through vertical transmission. The initial therapeutic strategy for the management of the virus was only the prevention of opportunistic infections. Later in the mid-1990s, antiretroviral therapy was introduced but there was no significant improvement in prognosis. After the advent of combination therapy or the use of three antiretroviral drugs also known as highly active antiretroviral therapy, there has been a marked reduction in human immunodeficiency virus-associated mortality rates. The highly active antiretroviral therapy has several effects on the oral manifestations of the human immunodeficiency virus. The present paper aims to review the oral pigmented lesions associated with human immunodeficiency virus with an emphasis on the effect of highly active antiretroviral therapy., Competing Interests: Declaration of Competing of Interest The authors declare that they have no conflict of interest, (Copyright © 2021. Published by Elsevier Inc.)

Human immunodeficiency virus-infected patients have depleted CD4 lymphocyte counts and are susceptible to a plethora of infections of bacterial, viral, and fungal etiology. In addition to a wide range of systemic manifestations, human immunodeficiency virus-infected patients also display several characteristic oral manifestations. Studies have shown a correlation between some of the oral manifestations and CD4 lymphocyte counts which in turn is an independent prognostic indicator. To tackle the human immunodeficiency virus numerous drugs have been discovered and implemented. To overcome any potential resistance, human immunodeficiency virus patients are prescribed highly active antiretroviral therapy, wherein a combination of antiretroviral regimens are used. Studies have shown that in addition to controlling the viral activity, the treatment regimen, has a significant effect on the oral manifestations of the human immunodeficiency virus-infected patients. The present paper highlights the effects of highly active antiretroviral therapy on periodontal diseases in human immunodeficiency virus-infected individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Human immunodeficiency virus has plagued mankind since the 1980's when the first case was documented. Human immunodeficiency virus-induced immunocompromised state can lead to several systemic and local manifestations, which often culminates in mortality. Oral candidiasis was one of the most prevalent opportunistic infections noted in human immunodeficiency virus-infected patients. The advent of highly active antiretroviral therapy has led to a significant reduction in both the mortality and the morbidity of infected patients. The combined antiretroviral therapy has also led to a decrease in the incidence of opportunistic infections including oral candidiasis. Thus, the presence of well-established oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy could be considered as an indicator of potential treatment failure. The present manuscript aims to review the published literature assessing the effect of highly active antiretroviral therapy on the incidence of oral candidiasis in human immunodeficiency virus-infected patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Globally, HIV/AIDS and cancer are increasingly public health problems and continue to exist as comorbidities. The sub-Saharan African region has the largest number of HIV infections. Malignancies previously associated with HIV/AIDS, also known as the AIDS-defining cancers (ADCs) have been documented to decrease, while the non-AIDS defining cancer (NADCs) are on the rise. On the other hand, cancer is a highly heterogeneous disease and precision oncology as the most effective cancer therapy is gaining attraction. Among HIV-infected individuals, the increased risk for developing cancer is due to the immune system of the patient being suppressed, frequent coinfection with oncogenic viruses and an increase in risky behavior such as poor lifestyle. The core of personalised medicine for cancer depends on the discovery and the development of biomarkers. Biomarkers are specific and highly sensitive markers that reveal information that aid in leading to the diagnosis, prognosis and therapy of the disease. This review focuses mainly on the risk assessment, diagnostic, prognostic and therapeutic role of various cancer biomarkers in HIV-positive patients. A careful selection of sensitive and specific HIV-associated cancer biomarkers is required to identify patients at most risk of tumour development, thus improving the diagnosis and prognosis of the disease.

After human immunodeficiency virus type 1 (HIV-1) was identified in the early 1980s, intensive work began to understand the molecular basis of HIV-1 gene expression. Subgenomic HIV-1 RNA regions, spread throughout the viral genome, were described to have a negative impact on the nuclear export of some viral transcripts. Those studies revealed an intrinsic RNA code as a new form of nuclear export regulation. Since such regulatory regions were later also identified in other viruses, as well as in cellular genes, it can be assumed that, during evolution, viruses took advantage of them to achieve more sophisticated replication mechanisms. Here, we review HIV-1 cis- acting repressive sequences that have been identified, and we discuss their possible underlying mechanisms and importance. Additionally, we show how current bioinformatic tools might allow more predictive approaches to identify and investigate them.

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 10 6 /kg body weight) or low-dose (0.5 × 10 6 /kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose (P < 0.001) and low-dose (P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS), a global pandemic that has claimed 32.7 million lives since 1981. Despite decades of research, there is no cure for the disease, with 38 million people currently infected with HIV. Attractive therapeutic targets for drug development are mature HIV-1 capsids, immature Gag polyprotein assemblies, and Gag maturation intermediates, although their complex architectures, pleomorphism, and dynamics render these assemblies challenging for structural biology. The recent development of integrative approaches, combining experimental and computational methods has enabled atomic-level characterization of structures and dynamics of capsid and Gag assemblies, and revealed their interactions with small-molecule inhibitors and host factors. These structures provide important insights that will guide the development of capsid and maturation inhibitors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In the era of anti-retroviral therapy (ART), the plasma HIV viral load (VL) is an important primary indicator for monitoring the HIV treatment response. To optimize the clinical management of HIV/AIDS patients, we investigated VL high-risk events related to virological failure (VF) and further explored the preventive factors of VL high-risk events., Methods: The data were derived from China's HIV/AIDS Comprehensive Response Information Management System. HIV infected patients who initiated or received ART in Guangxi between 2003 and 2019 were included. The contributions of VL after 6 months of ART to VF and AIDS-related death were analysed by Kaplan-Meier curves, log-rank tests and Cox regression analyses. Both descriptive analyses and bivariate logistic regression were employed to further explore the preventive factors related to VL high-risk events of VF., Results: The cumulative rates of VF in the high low-level viremia group (high LLV) (χ 2  = 18.45; P <  0.001) and non-suppressed group (χ 2  = 82.99; P <  0.001) were significantly higher than those in the viral suppression (VS) group. Therefore, the VL high-risk events of VF was defined as highest VL > 200 copies/ml after 6 months of ART. Compared with the VS group, the adjusted hazard risk was 7.221 (95% CI: 2.668; 19.547) in the high LLV group and 8.351 (95% CI: 4.253; 16.398) in the non-suppressed group. Compared with single patients, married or cohabiting (AOR = 0.591; 95% CI: 0.408, 0.856) and divorced or separated (AOR = 0.425, 95% CI: 0.207, 0.873) patients were negatively associated with VL high-risk events. So were patients acquired HIV homosexually (AOR = 0.572; 95% CI: 0.335, 0.978). However, patients who had ART modification were 1.728 times (95% CI: 1.093, 2.732) more likely to have VL high-risk events, and patients who used cotrimoxazole during ART were 1.843 times (95% CI: 1.271, 2.672) more likely to have VL high-risk events., Conclusions: A VL greater than 200 copies/ml is a VL high-risk event for VF. Intervention measurements should be adopted to optimize the surveillance of ART in patients who are single or widowed, who have ART modification, and who use cotrimoxazole during ART.

In 2006 we discovered a new type of mucosal vaccine against simian immunodeficiency virus (SIV) in Chinese macaques. Here, we review 15 years of our published work on this vaccine, which consists of inactivated SIVmac239 particles adjuvanted with Bacillus Calmette-Guérin, Lactobacillus plantarum, or Lactobacillus rhamnosus. Without adjuvant, the vaccine administered by the intragastric route induced the usual SIV-specific humoral and cellular immune responses but provided no protection against intrarectal challenge with SIVmac239. In contrast, out of 24 macaques immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to five years, while all control macaques were infected. This protection was confirmed by an independent group from the Pasteur Institute. During the past 15 years, we have identified the mechanism of action of the vaccine and discovered that the vaccinated macaques produced a previously unrecognized class of MHC-Ib/E-restricted CD8 + T cells (which we refer to as tolerogenic CD8 + T cells) that suppressed the activation of SIV-RNA-infected CD4 + T cells and thereby inhibited the (activation-dependent) reverse transcription of the virus, which in turn prevented the establishment of SIV infection. Importantly, we discovered also that the tolerogenic CD8 + T cell subset observed in vaccinated Chinese macaques could also be found in human elite controllers, a small group of HIV-infected patients in whom these tolerogenic CD8 + T cells were shown to naturally suppress viral replication. Given that SIV and HIV require activated immune cells in which to replicate, the specific prevention of activation of SIV-RNA-containing CD4 + T cells by a tolerogenic vaccine approach offers an exciting new avenue in HIV vaccine research.

Acquired immune deficiency syndrome (AIDS) has prevailed over the last 30 years. Although highly active antiretroviral therapy (HAART) has decreased mortality and efficiently controlled the progression of disease, no vaccine or curative drugs have been approved until now. A viral inactivator is expected to inactivate cell-free virions in the absence of target cells. Previously, we identified a gp120-binding protein, mD1.22, which can inactivate laboratory-adapted HIV-1. In this study, we have found that the gp41 N-terminal heptad repeat (NHR)-binding antibody D5 single-chain variable fragment (scFv) alone cannot inactivate HIV-1 at the high concentration tested. However, D5 scFv in the combination could enhance inactivation activity of mD1.22 against divergent HIV-1 strains, including HIV-1 laboratory-adapted strains, primary HIV-1 isolates, T20- and AZT-resistant strains, and LRA-reactivated virions. Combining mD1.22 and D5 scFv exhibited synergistic effect on inhibition of infection by divergent HIV-1 strains. These results suggest good potential to develop the strategy of combining a gp120-binding protein and a gp41-binding antibody for the treatment of HIV-1 infection.

Background: HIV is a major global public health challenge, claiming the lives of over 32 million people so far. The satisfaction of HIV-affected clients with the quality of their HIV services at treatment centres is crucial for quality improvement. This article assesses clients' satisfaction with different aspects of the overall care experience and seeks to determine if the type of health facility ownership is a predictor of satisfaction., Methods: A cross-sectional study involving 430 respondents was conducted between September and October 2019. Purposeful and convenient sampling techniques were used to select health facilities and potential respondents, respectively. A pre-tested, interviewer-administered questionnaire was used to collect data. Binary logistic regression was used to assess the association between type of health facility and clients' satisfaction based on the six assessed aspects of care, and p˂0.05 was considered statistically significant., Results: The general clients' satisfaction with HIV/AIDS services at care and treatment centres was 92.3%. Respondents from public health facilities were most satisfied with privacy and confidentiality (100%), physical environment (100%), counseling (99.5%) and drug availability (99.5%); respondents from private health facilities were most satisfied with the time spent in the facility (95.9%); while respondents from faith-based health facilities were most satisfied with staff-patient communication (99.2%). However, after adjusting for confounders, only one aspect of care, that of "time spent in the facility," showed significant association with the type of health facility., Conclusion: Generally, clients' satisfaction with HIV/AIDS services at care and treatment centres in the Ubungo District, Dar es Salaam was high. This finding should encourage health care providers to maintain high-quality services to sustain clients' satisfaction., Competing Interests: The authors have declared that no competing interests exist.

Kaposi's sarcoma (KS) has been the most common HHV-8 virus-induced neoplasm associated with HIV-1 infection. Although the standard KS therapy has not changed in 20 years, not all cases of KS will respond to the same therapy. The goal of current AIDS-KS treatment modalities is to reconstitute the immune system and suppress HIV-1 replication, but newer treatment modalities are on horizon. There are very few mathematical models that have included HIV-1 viral load (VL) measures, despite VL being a key determinant of treatment outcome. Here we introduce a mathematical model that consolidates the effect of both HIV-1 and HHV-8 VL on KS tumor progression by incorporating low or high VLs into the proliferation terms of the immune cell populations. Regulation of HIV-1/HHV-8 VL and viral reservoir cells is crucial for restoring a patient to an asymptomatic stage. Therefore, an optimal control strategy given by a combined antiretroviral therapy (cART) is derived. The results indicate that the drug treatment strategies are capable of removing the viral reservoirs faster and consequently, the HIV-1 and KS tumor burden is reduced. The predictions of the mathematical model have the potential to offer more effective therapeutic interventions based on viral and virus-infected cell load and support new studies addressing the superiority of VL over CD4 + T-cell count in HIV-1 pathogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ending the AIDS epidemic by 2030 will require addressing stigma more systematically and at a larger scale than current efforts. Existing global evidence shows that stigma is a barrier to achieving each of the 90-90-90 targets; it undermines HIV testing, linkage to care, treatment adherence, and viral load suppression. However, findings from both research studies and programmatic experience have helped to inform the growing body of knowledge regarding how to reduce stigma, leading to key principles for HIV stigma reduction. These principles include immediately addressing actionable drivers of stigma, centring groups affected by stigma at the core of the response, and engaging opinion leaders and building partnerships between affected groups and opinion leaders. Although there is still room to strengthen research on stigma measurement and reduction, in particular for intersectional stigma, the proliferation of evidence over the past several decades on how to measure and address stigma provides a solid foundation for immediate and comprehensive action., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The ability for viruses to mutate and evade the human immune system and cause infection, called viral escape, remains an obstacle to antiviral and vaccine development. Understanding the complex rules that govern escape could inform therapeutic design. We modeled viral escape with machine learning algorithms originally developed for human natural language. We identified escape mutations as those that preserve viral infectivity but cause a virus to look different to the immune system, akin to word changes that preserve a sentence's grammaticality but change its meaning. With this approach, language models of influenza hemagglutinin, HIV-1 envelope glycoprotein (HIV Env), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike viral proteins can accurately predict structural escape patterns using sequence data alone. Our study represents a promising conceptual bridge between natural language and viral evolution., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Understanding the demographic characteristics of people living with HIV/AIDS (PLWHA) infected through commercial heterosexual contact (CHC) or nonmarital noncommercial heterosexual contact (NMNCHC) is important for HIV/AIDS prevention and control., Methods: Cases reported through the Chinese HIV/AIDS Case Reporting System (CRS) from 2015 to 2018 were analyzed. A descriptive and preliminary inferential analysis were performed for those demographic characteristics deemed of interest., Results: Overall, 523,121 identified PLWHA between 2015 and 2018 in the CRS were analyzed. The constituent ratio of heterosexual transmission increased from 66.25% in 2015 to 71.48% in 2018. The proportion of CHC heterosexual transmission decreased from 40.18% in 2015 to 37.99% in 2018, while that of NMNCHC increased from 46.33% in 2015 to 49.02% in 2018. PLWHA infected through NMNCHC were significantly younger than those who were infected through CHC (Student's t test, P < 0.0001), with an average age gap ranging from 5.63 (2015) to 7.46 (2018) years, and the average age of both groups increased annually. The frequency of newly identified PLWHA who were infected through CHC had a remarkable increase among the ages of 65 and above. Gender distribution was significantly different between CHC and NMNCHC (χ 2  = 8909.00(2015), 9941.90(2016), 11,004.00 (2017), 12,836.00(2018), all P < 0.0001), and the ratio of men to women in the NMCHC group was 1.50:1 (2015), 1.51:1 (2016), 1.54:1 (2017), and 1.52:1 (2018), while in the commercial heterosexual contact (CHC) group, these ratios were 11.45:1 (2015), 12.08:1 (2016), 12.53:1 (2017), and 13.28:1 (2018). Marital status was significantly different between CHC and NMNCHC (χ 2  = 94.67 (2015), 109.88(2016), 58.18(2017), 152.38(2018), all P < 0.0001). As the educational level improved, the proportion of NMNCHC also increased (Cochran - Armitage test, P < 0.0001)., Conclusions: We found that heterosexual transmission was the primary mode of HIV transmission in China from 2015 to 2018. PLWHA infected through CHC and NMNCHC had different characteristics in age, gender, marital status, and educational level. The frequency of PLWHA infected through CHC increased substantially in the age group of 65 and above. This study provides useful baseline data for future studies on the heterosexual transmission of HIV in China.

Background: Human immunodeficiency virus (HIV)/AIDS is one of the principal concerns contributing to the global burden and the accompanying deleterious outcomes could not be left unattended. Despite significant advances and innovative research being conducted throughout the globe in order to improve the therapeutic profile of conventionally available antiretroviral (ARV) drugs in the eradication of HIV virus reservoirs, its penetration across the blood-brain barrier (BBB) is still a formidable mission. This makes the central nervous system a dominant and vulnerable site for virus propagation, which ultimately affects the therapeutic potential of the drug administered. Therefore there is an upsurge in the prerequisite of novel technologies to come into play, paving the way for nanotechnology., Methods: This review primarily provides a comprehensive outline and emphasizes on the nanotechnological techniques employed for the delivery of ARV drugs and their stupendous advantages in overcoming the hurdles associated with the same., Results: The nanotechnological approach bears the potential of site-specific delivery across the BBB via targeting explicit transport processes and provides a sustained release mechanism. Furthermore, different routes of administration explored have also yielded beneficial outcomes for the delivery of ARV drugs., Conclusion: The futuristic holistic nanotechnology methods, however, should focus on increasing drug trafficking and permeability across the BBB to ameliorate the therapeutic effect of ARV drugs. Additionally, the domain warrants clinical studies to be undertaken to make the technology commercially viable and a success to deal with the problems of the treatment strategy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

With the introduction of antiretroviral therapy, the worldwide AIDS-related deaths have decreased, and life expectancy has increased, including the prevalence of AIDS-related neurological disorders or neuroAIDS. HIV-associated neurocognitive disorders such as mild neurocognitive disorder and asymptomatic neurocognitive impairment have largely remained stable or increased among the HIV-infected individuals in the combination antiretroviral therapy era. The emerging evidence that antiretrovirals with high CNS penetration effectiveness score contribute to the neurotoxicity and HIV-associated neurocognitive disorders has ushered the search for natural, nontoxic bioactive constituents having pre-established neuroprotective, anti-inflammatory, and restorative neurocognitive activity. In this review, we have highlighted the probable mechanism of neuroAIDS infection, the problem with the existing antiretroviral therapy, along with various bioactive constituents with in vivo, in vitro, or ex vivo evidence of their neuroprotective activity that can be used as an adjuvant with the current combination antiretroviral therapy regimen or can even serve as an alternate to the antiretrovirals for treatment of HIV associated neurocognitive disorder., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study assessed the determinants that shape HIV knowledge and attitudes among South Sudanese women by analysing a Multiple Indicator Cluster Survey collected from 9,061 women in 9,369 households. Generalised linear mixed model regression was performed. Fifty percent of respondents were aware of HIV/AIDS, with 21% and 22% exhibiting good knowledge and positive attitudes towards people with HIV/AIDS, respectively. When controlled for individual and community-level variables, younger women (AOR = 1.28, 95% CI: 1.01-162), women with primary (AOR = 2.19; 95% CI: 1.86-2.58) and secondary (AOR = 4.48; 95% CI: 3.38-5.93) education, and those living in urban areas (AOR = 1.40; 95% CI: 1.12-1.76) had significantly good knowledge. Women in the richer (AOR = 1.60; 95% CI: 1.08-2.36) and the richest (AOR = 2.02; 95% CI: 1.35-3.02) wealth quintiles had significant positive attitudes towards people with HIV/AIDS. Well-designed social and behavioural campaigns targeting uneducated women and those living in rural and remote settings will enhance knowledge of perceived risk, awareness, and ability to carry out preventive behaviours., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The tear, as an important bodily secretion, plays a crucial role in preventing infection and maintaining homeostasis of ocular surfaces. Although accumulating studies have reported on the HIV-1 viral load profile among varying bodily fluids and secretions, little was known concerning HIV-1 dynamics in tears. Therefore, the objectives of this study were to investigate the HIV-1 viral load in tears of HIV/AIDS patients and study factors influencing their tear viral load., Methods: A cross-sectional study was conducted. 67 patients with a confirmed HIV-1 infection or AIDS were recruited from the Beijing You'an Hospital, China between April 2018 and September 2018. Socio-demographic information and laboratory test results were collected. At the same time, ophthalmic examinations were carried out and tear samples were tested., Results: Of 30 highly active antiretroviral therapy (HAART)-naïve patients, 53.3% had detectable HIV-1 RNA in tears. Of 37 patients on HAART, HIV-1 RNA was undetectable in their tears, regardless of treatment duration and blood viral load. Tear viral load ranged from TND (target not detected) to 13,096 copies/mL. Viral load was lower in tears than in blood plasma (p < 0.001), and was significantly correlated with plasma viral load (Rho = 0.566, p < 0.001) and AIDS stage (Rho = 0.312, p = 0.01), but negatively correlated with CD4  +  T cell count, CD4  + /CD8  +  T cell count, and duration of HIV infection (Rho = -0.450, Rho = - 0.464, Rho = - 0.565; p < 0.001)., Conclusions: HIV-1 RNA is present in tears of more than half of the HAART-naïve patients, whereas absent in tears of patients on HAART. Tear viral load is positively associated with plasma viral load while it is negatively correlated with CD4 cell count. This study provides novel insights into the area with limited understanding-HIV-1 viral load in tears.

Rhodococcus equi emerged as a zoonotic pathogen of human immunodeficiency virus-infected patients over the last three decades. Two virulence plasmid types of R. equi, pVAPA and pVAPB associated with equine and porcine isolates, have been recognized, and more recently, pVAPN, a novel host-associated virulence plasmid in R. equi, was found in bovine and caprine isolates. We reinvestigated 39 previously reported isolates of R. equi from patients with and without acquired immunodeficiency syndrome (AIDS) by detecting vapA, vapB and vapN using PCR and plasmid profiling. After excluding one isolate that could not be cultured from frozen storage, eight isolates carried a virulence plasmid encoding vapA (pVAPA), 10 carried a virulence plasmid encoding vapB (pVAPB), seven carried a virulence plasmid encoding vapN (pVAPN) and 13 were negative for those genes. Of the 29 isolates from patients with AIDS, 7, 10 and 5 harboured pVAPA, pVAPB and pVAPN respectively. Among nine isolates from patients without AIDS, one and two harboured pVAPA and pVAPN respectively. This study demonstrated that pVAPN-positive R. equi existed in human isolates before 1994 and reaffirmed that equine-associated pVAPA-positive, porcine-associated pVAPB-positive and bovine- or caprine-associated pVAPN-positive R. equi are widely spread globally. Because domestic animals might be major sources of human infection, further research is needed to reveal the prevalence of pVAPN-positive R. equi infection in cattle and goats., (© 2020 The Society for Applied Microbiology.)

Background: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district., Methods: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data., Results: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation., Conclusions: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.

To determine the surgical outcomes and prognostic factors of cytomegalovirus (CMV) retinitis-related retinal detachment (RD) in acquired immune deficiency syndrome (AIDS) patients following vitrectomy.A retrospective charts review was carried out on AIDS patients who were diagnosed with CMV retinitis-related RD and treated with vitrectomy between 2002 and 2016. The main outcome measures were the rates of primary anatomical success and final visual acuity (VA) success defined as postoperative VA ≥20/200. Kaplan-Meier curves on the time to retinal redetachment were performed. Multivariate logistic regression models based on a directed acyclic graph were used to identify independent factors associated with achieving VA success.Forty five AIDS patients (52 eyes) were included. Over a mean follow-up period of 41.7 months, primary anatomical success was achieved in 44 eyes (84.6%) and VA success was achieved in 34 eyes (65.4%). Receiving highly active antiretroviral therapy (HAART) prior to RD (adjusted odds ratio [aOR]=4.9, P = .043), better preoperative VA (aOR = 4.3, P = .006), undergoing vitrectomy within 3 months (aOR=6.7, P = .008), absence of optic atrophy (aOR=58.1, P < .001), and absence of retinal redetachment (aOR=38.1, P = .007) increased the odds of achieving final VA success.Vitrectomy provided favorable anatomical reattachment in AIDS patients with CMV retinitis-related RD. Majority of patients was able to retain functional vision postoperatively. The use of HAART and early vitrectomy increased the probability of achieving both anatomical and VA success.

Objectives: The aim of the study was to systematically review current studies reporting on clinical outcomes in people living with HIV (PLHIV) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was conducted in Global Health, SCOPUS, Medline and EMBASE using pertinent key words and Medical Subject Headings (MeSH) terms relating to coronavirus disease 2019 (COVID-19) and HIV. A narrative synthesis was undertaken. Articles are summarized in relevant sections., Results: Two hundred and eighty-five articles were identified after duplicates had been removed. After screening, eight studies were analysed, totalling 70 HIV-infected patients (57 without AIDS and 13 with AIDS). Three themes were identified: (1) controlled HIV infection does not appear to result in poorer COVID-19 outcomes, (2) more data are needed to determine COVID-19 outcomes in patients with AIDS and (3) HIV-infected patients presenting with COVID-19 symptoms should be investigated for superinfections., Conclusions: Our findings suggest that PLHIV with well-controlled disease are not at risk of poorer COVID-19 disease outcomes than the general population. It is not clear whether those with poorly controlled HIV disease and AIDS have poorer outcomes. Superimposed bacterial pneumonia may be a risk factor for more severe COVID-19 but further research is urgently needed to elucidate whether PLHIV are more at risk than the general population., (© 2020 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Coinfections of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with high morbidity and mortality and poor prognosis. The main objective of this study was to evaluate the prevalence of HCV and/or HBV coinfections among people who inject drugs (PWID) and female sex workers (FSWs) who live with HIV/AIDS worldwide. Data sources were searched from January 2008 to October 2018 in different databases, including PubMed, Scopus, Web of Science, Embase, and Ovid. Data were analyzed in Stata 14 software using the Metaprop command. The results showed that the prevalence of HCV among PWID and FSWs with HIV/AIDS was 72% (95% CI: 59%-83%) and 40% (95% CI: 0%-94%), respectively. The prevalence of HBV among PWID and FSWs with HIV/AIDS was 8% (95% CI: 5%-13%) and 2% (95% CI: 0%-7%), respectively, and the prevalence of HCV/HBV in PWID with HIV/AIDS was 11% (95% CI: 7%-15%). The highest prevalence of HCV was observed in PWID in the Eastern Mediterranean and Europe regions, and the lowest was observed in the Africa region. The South-East Asia region had the highest prevalence of HBV among PWID, and the Africa region had the lowest prevalence. The high prevalence of HCV coinfection among PWID and FSWs with HIV/AIDS was an alarming health problem and requires appropriate interventions. Therefore, considering that these populations are key populations for HCV elimination, it is recommended to screen them regularly for HCV. In addition, harm reduction and HBV vaccination should be carefully considered.

Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients.

Background: Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4 + T cells (CD4 + TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4 + TC levels without the use of antiretroviral therapy (ART)., Methods: The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4 + TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations., Results: Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations., Conclusion: The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.

Anti-retroviral therapy (ART) can inhibit HIV proliferation but not achieve virus eradication from HIV-infected individuals. Under ART-based HIV control, virus-specific CD8 + T-cell responses are often reduced. Here, we investigated the impact of therapeutic vaccination inducing virus-specific CD8 + T-cell responses under ART on viral control in a macaque AIDS model. Twelve rhesus macaques received ART from week 12 to 32 after simian immunodeficiency virus (SIV) infection. Six of them were vaccinated with Sendai virus vectors expressing SIV Gag and Vif at weeks 26 and 32, and Gag/Vif-specific CD8 + T-cell responses were enhanced and became predominant. All macaques controlled viremia during ART but showed viremia rebound after ART cessation. Analysis of in vitro CD8 + cell ability to suppress replication of autologous lymphocytes-derived SIVs found augmentation of anti-SIV efficacy of CD8 + cells after vaccination. In the vaccinated animals, the anti-SIV efficacy of CD8 + cells at week 34 was correlated positively with Gag-specific CD8 + T-cell frequencies and inversely with rebound viral loads at week 34. These results indicate that Gag-specific CD8 + T-cell induction by therapeutic vaccination can augment anti-virus efficacy of CD8 + cells, which may be insufficient for functional cure but contribute to more stable viral control under ART.

The main aim of this study was to test whether perception of partner infidelity prompts people to adopt behaviour that is meant to compensate for the increased risk of infection posed by their partner's infidelity; or whether it prompts people to engage in behaviour that magnifies the risk associated with partner infidelity. Data used were derived from the fourth and latest Botswana AIDS Impact Survey (BAIS IV) conducted in 2013. The sample consisted of 6985 people aged 10-34 years. Logistic regression analysis was used to identify factors associated with perception of partner infidelity and sexual risk behaviours. Perception of partner infidelity with the current and most recent partner was 39.6% while perception of partner infidelity with other previous sexual partners was 79.9%. The main socio-demographic factors associated with perception of partner infidelity were being a man, being single and having secondary education, while sexual risk behaviours associated with perception of partner infidelity were having multiple sexual partners and being involved in multiple concurrent sexual partnerships. These relationships were statistically significant at the 5% level. Botswana's HIV prevention strategies should seek to improve partner communication within relationships in order to enhance people's confidence and skills so as to minimize perceptions of infidelity.

Background: Sleep is a natural, restorative, physiological process that is characterized by perceptual disengagement from and unresponsiveness to whatever going around, which is reversible. Sleep quality refers to a sense of being rested and refreshed after waking up from sleep. People living with HIV/AIDS (PLWHA) are vulnerable to poor sleep quality as they suffer from social stigma and Anti-Retroviral drug side effects. The study aimed to examine the quality of sleep and its associated factors among people living with HIV/AIDS attending Anti-Retroviral Therapy (ART) clinic at Hawassa University comprehensive specialized hospital., Method: Institutional based cross-sectional study was conducted among PLWHA attending ART clinic at Hawassa University comprehensive specialized hospital from May 1-30, 2019. A systematic random sampling technique was used to select an estimated 422 study participants and data was collected using interviewer-administered technique. Sleep Quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Data were entered and analyzed using SPSS 22 software. Bivariable and multivariable logistic regression model was fitted to identify factors associated with quality of sleep. An adjusted odds ratio with a 95% confidence interval was computed to determine the level of significance with P-value less than 0.05., Result: Out of 422 respondents, 389 participated in the study giving a response rate of 92.1%. The prevalence of poor quality of sleep among study participants was found to be 57.6% (95% CI: 54.72, 60.48). 31.9% (124) and 30.6% (119) of study participants had anxiety and depression respectively. Being between the age of 55-64 years (AOR = 5.7, 95% CI (1.9, 17.8), Age ≥ 65 (AOR:6.6, 95% CI (1.2, 36.9), Monthly income <1656 Ethiopian Birr (ETB) (AOR = 2.17, 95% CI (1.06, 4.4), having anxiety (AOR = 4.4, 95% CI (2.12, 9.2), having depression (AOR = 4.97, 95% CI (2.28, 10) and poor social support (AOR = 2.9, 95% CI (1.16, 7.3) were factors associated with poor quality of sleep., Conclusion: The prevalence of poor quality of sleep among PLWHA was significantly high. Average monthly income, age, anxiety, depression, and social support were found to be significantly associated with poor sleep quality. Health care professionals working at the ART clinic need to assess the sleep pattern of ART clients, give psychoeducation on the prevention and management of sleep pattern problems., Competing Interests: The authors have declared that no competing interests exist.

Background: Disclosure of Human Immunodeficiency Virus positive status significantly reduced the transmission of HIV; yet, it remains a challenge for many HIV patients. Disclosure serves plays a crucial role to raise awareness and to reduce risky behaviors. Hence, this study aimed to determine the pooled prevalence and effect sizes of determinant factors of HIV positive status disclosure through a systematic review and meta-analysis of the results of the existing primary studies in Ethiopia., Method: This systematic review and meta-analysis was aimed to determine prevalence of HIV positive status disclosure and associated factors by considering and searching published primary articles from different sources. A sensitivity test was conducted to evaluate the presence of influential studies. Besides, the heterogeneity test has been conducted; and publication bias was examined through observing the funnel plot as well as objectively by interpreting the Egger's regression test. Following the Egger's regression test, P-value < 0.05 was considered as statistically significant at 95% Confidence Interval., Result: A total of 18 primary studies were searched from different data sources. The overall pooled prevalence of HIV positive status disclosure among adult PLWHA in Ethiopia was indicated to be 75.95% (95% CI:69.93-81.98); the highest and lowest pooled estimated HIV status disclosure was in Amhara (82.78%) and Tigray (54.31%) regions respectively. Furthermore, Knowing the HIV positive status of sexual partner, AOR = 19.66(95% CI: 10.19-37.91), having prior discussion about HIV testing with their partner, AOR = 9.18(95% CI: 5.53-15.24), got Human Immunodeficiency Virus pretest counseling service AOR = 4.29(95% CI: 2.56-7.21) and being a member of HIV/AIDS associations, AOR = 3.34(95% CI: 2.17-5.12), were significantly associated with HIV positive status disclosure among People living With HIV/AIDS in Ethiopia., Conclusion: The pooled national estimate of HIV/AIDS positive status disclosure is low as compared to the WHO disclosure rate of developing countries and the findings of other national and international studies. Ministry of health and other stakeholders shall design new approaches and strategies to encourage disclosure of HIV status, educate the public about the negative impact of nondisclosure within family members. Health care providers working at Human HIV test centers shall emphasis extensive counseling on disclosure of status to a partner. Moreover, different stakeholders, health workers and community members shall establish, organize, and support HIV/AIDS Associations and motivate HIV positive people to be engaged and participated.

Purpose: The Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) Program Evaluation (SHAPE) study is a longitudinal cohort developed to monitor the progress of an HIV testing and treatment expansion programme across the province of British Columbia (BC). The study considers how sociostructural determinants such as gender, age, sexual identity, geography, income and ethnicity influence engagement in HIV care., Participants: Between January 2016 and September 2018, 644 BC residents who were at least 19 years old and diagnosed with HIV were enrolled in the study and completed a baseline survey. Participants will complete two additional follow-up surveys (18 months apart) about their HIV care experiences, with clinical follow-up ongoing., Findings to Date: Analyses on baseline data have found high levels of HIV care engagement and treatment success among SHAPE participants, with 95% of participants receiving antiretroviral therapy and 90% having achieved viral suppression. However, persistent disparities in HIV treatment outcomes related to age, injection drug use and housing stability have been identified and require further attention when delivering services to marginalised groups., Future Plans: Our research will examine how engagement in HIV care evolves over time, continuing to identify barriers and facilitators for promoting equitable access to treatment and care among people living with HIV. A qualitative research project, currently in the formative phase, will compliment quantitative analyses by taking a strengths-based approach to exploring experiences of engagement and re-engagement in HIV treatment among individuals who have experienced delayed treatment initiation or treatment interruptions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objectives: Nontuberculous mycobacteria (NTM) are opportunistic agents that have gained importance during the last decades due to their increasing incidence in high-risk populations. Their modes of transmission differ from person-toperson contact commonly described in Mycobacterium tuberculosis (MTB). In fact, NTM are frequently found in soil, natural waters and drinking-water distributions systems, emphasizing the contribution of environmental factors when discussing this disease's susceptibility. Our aim is to evaluate the incidence of NTM in Portugal and to identify the main environmental variables related to it., Material and Methods: We performed a cross-sectional study centred on 2011 (date of the latest Portuguese census) from collected personal features and environmental data available in public databases. Environmental values when only known at the district level were interpolated using inverse distance weighting. A semiparametric poisson model was used to estimate NTM incidence. The non-parametric part of the model was obtained by using thin plate smoothing splines defined on the spatial component of the data., Results: 359 new NTM cases were notified during a five-year period. None of the environmental determinants studied was strong enough to predict NTM geographical incidence in Portugal (p>0.05), except for population density (p<0.001). Personal characteristics such as female sex (p<0.001), age (p<0.001) and Human Immunodeficiency Virus infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) incidence (p<0.001) are associated with an increase of NTM disease incidence., Conclusions: NTM appears to be more common in elderly women, especially if they have HIV/AIDS disease or if they live in urban, highly populated areas. Overall, female sex seems to assume the most relevant role when discussing predisposition to NTM disease. However, further studies are needed to evaluate the impact on NTM geographical incidence by other environmental and personal variables not included in this one., (Copyright © 2019 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Acquired Immune Deficiency Syndrome (AIDS) treatment with combination antiretroviral therapy (cART) has improved the life quality of many patients since its implementation. However, resistance mutations and the accumulation of severe side effects associated with cART remain enormous challenges that need to be addressed with the continual design and redesign of anti-HIV drugs. In this review, we focus on the importance of the HIV-1 Gag polyprotein as the master coordinator of HIV-1 assembly and maturation and as an emerging drug target. Due to its multiple roles in the HIV-1 life cycle, the individual Gag domains are attractive but also challenging targets for inhibitor design. However, recent encouraging developments in targeting the Gag domains such as the capsid protein with highly potent and potentially long-acting inhibitors, as well as the exploration and successful targeting of challenging HIV-1 proteins such as the matrix protein, have demonstrated the therapeutic viability of this important protein. Such Gag-directed inhibitors have great potential for combating the AIDS pandemic and to be useful tools to dissect HIV-1 biology.

Background: Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain., Methods: Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs., Results: At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA <200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA <200 copies/mL at week 96., Conclusions: HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of >2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression., Clinical Trials Registration: NCT00537394., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Patients infected with HIV may experience a succession of clinical stages before the disease diagnosis and their health status may be followed-up by tracking disease biomarkers. In this study, we present a joint multistate model for predicting the clinical progression of HIV infection which takes into account the viral load and CD4 count biomarkers., Methods: The data is from an ongoing prospective cohort study conducted among antiretroviral treatment (ART) naïve HIV-infected women in the province of KwaZulu-Natal, South Africa. We presented a joint model that consists of two related submodels: a Markov multistate model for CD4 cell count transitions and a linear mixed effect model for longitudinal viral load dynamics., Results: Viral load dynamics significantly affect the transition intensities of HIV/AIDS disease progression. The analysis also showed that patients with relatively high educational levels (β = - 0.004; 95% confidence interval [CI]:-0.207, - 0.064), high RBC indices scores (β = - 0.01; 95%CI:-0.017, - 0.002) and high physical health scores (β = - 0.001; 95%CI:-0.026, - 0.003) were significantly were associated with a lower rate of viral load increase over time. Patients with TB co-infection (β = 0.002; 95%CI:0.001, 0.004), having many sex partners (β = 0.007; 95%CI:0.003, 0.011), being younger age (β = 0.008; 95%CI:0.003, 0.012) and high liver abnormality scores (β = 0.004; 95%CI:0.001, 0.01) were associated with a higher rate of viral load increase over time. Moreover, patients with many sex partners (β = - 0.61; 95%CI:-0.94, - 0.28) and with a high liver abnormality score (β = - 0.17; 95%CI:-0.30, - 0.05) showed significantly reduced intensities of immunological recovery transitions. Furthermore, a high weight, high education levels, high QoL scores, high RBC parameters and being of middle age significantly increased the intensities of immunological recovery transitions., Conclusion: Overall, from a clinical perspective, QoL measurement items, being of a younger age, clinical attributes, marital status, and educational status are associated with the current state of the patient, and are an important contributing factor to extend survival of the patients and guide clinical interventions. From a methodological perspective, it can be concluded that a joint multistate model approach provides wide-ranging information about the progression and assists to provide specific dynamic predictions and increasingly precise knowledge of diseases.

Anti-retroviral therapy (ART) has been highly successful in controlling HIV replication, reducing viral burden, and preventing both progression to AIDS and viral transmission. Yet, ART alone cannot cure the infection. Even after years of successful therapy, ART withdrawal leads inevitably to viral rebound within a few weeks or months. Our hypothesis: effective therapy must control both the replicating virus pool and the reactivatable latent viral reservoir. To do this, we have combined ART and immunotherapy to attack both viral pools simultaneously. The vaccine regimen consisted of DNA vaccine expressing SIV Gag, followed by a boost with live attenuated rubella/gag vectors. The vectors grow well in rhesus macaques, and they are potent immunogens when used in a prime and boost strategy. We infected rhesus macaques by high dose mucosal challenge with virulent SIVmac251 and waited three days to allow viral dissemination and establishment of a reactivatable viral reservoir before starting ART. While on ART, the control group received control DNA and empty rubella vaccine, while the immunotherapy group received DNA/gag prime, followed by boosts with rubella vectors expressing SIV gag over 27 weeks. Both groups had a vaccine "take" to rubella, and the vaccine group developed antibodies and T cells specific for Gag. Five weeks after the last immunization, we stopped ART and monitored virus rebound. All four control animals eventually had a viral rebound, and two were euthanized for AIDS. One control macaque did not rebound until 2 years after ART release. In contrast, there was only one viral rebound in the vaccine group. Three out of four vaccinees had no viral rebound, even after CD8 depletion, and they remain in drug-free viral remission more than 2.5 years later. The strategy of early ART combined with immunotherapy can produce a sustained SIV remission in macaques and may be relevant for immunotherapy of HIV in humans., Competing Interests: The authors have read the journal's policy and declare the following potential competing interests: KEB was employed by a commercial company, Inovio Pharmaceuticals, Inc. and ML was employed by BioQual, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Objective: In 2014, the Joint United Nations Program on HIV and AIDS (UNAIDS) and partners set the '90-90-90 targets'. Many countries are facing the challenge of estimating the first 90. Our objective was to propose an alternative modelling procedure, and to discuss its usefulness for taking into account duplication., Results: For deduplication, we identified two important ingredients: the probability for an HIV+ person of being re-tested during the period and average number of HIV+ tests. Other adjusted factors included: the false positive probability; the death and emigration probabilities. The uncertainty of the adjusted estimate was assessed using the plausibility bounds and sensitivity analysis. The proposed method was applied to Cameroon for the period 1987-2016. Of the 560,000 people living with HIV estimated from UNAIDS in 2016; 504,000 out to know their status. The model estimates that 380,464 [379,257, 381,674] know their status (75.5%); thus 179,536 who do not know their status should be sought through the intensification of testing. These results were subsequently used for constructing the full 2016 Cameroon HIV cascade for identifying programmatic gap, prioritizing the resources, and guiding the strategies of the 2018-2022 National Strategy Plan and funding request.

Background: Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth., Methods: People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus., Results: Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62)., Discussion: These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)