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: Introduction: Social network strategies, in which social networks are utilized to influence individuals or communities, are increasingly being used to deliver human immunodeficiency virus (HIV) interventions to key populations. We summarized and critically assessed existing research on the effectiveness of social network strategies in promoting HIV self‐testing (HIVST). Methods: Using search terms related to social network interventions and HIVST, we searched five databases for trials published between 1st January 2010 and 30th June 2023. Outcomes included uptake of HIV testing, HIV prevalence and linkage to antiretroviral therapy (ART) or HIV care. We used network meta‐analysis to assess the uptake of HIV testing through social network strategies compared with control methods. A pairwise meta‐analysis of studies with a comparison arm that reported outcomes was performed to assess relative risks (RR) and their corresponding 95% confidence intervals (CI). Results: Among the 4496 manuscripts identified, 39 studies fulfilled the inclusion criteria, including one quasi‐experimental study, 22 randomized controlled trials and 16 observational studies. Networks HIVST testing was organized by peers (distributed to known peers, 15 studies), partners (distributed to their sexual partners, 16 studies) and peer educators (distributed to unknown peers, 8 studies). Among social networks, simulating the possibilities of ranking position, peer distribution had the highest uptake of HIV testing (84% probability), followed by partner distribution (80% probability) and peer educator distribution (74% probability). Pairwise meta‐analysis showed that peer distribution (RR 2.29, 95% CI 1.54−3.39, 5 studies) and partner distribution (RR 1.76, 95% CI 1.50−2.07, 10 studies) also increased the probability of detecting HIV reactivity during testing within the key population when compared to the control. Discussion: All of the three social network distribution strategies enhanced the uptake of HIV testing compared to standard facility‐based testing. Linkage to ART or HIV care remained comparable to facility‐based testing across the three HIVST distribution strategies. Conclusions: Network‐based HIVST distribution is considered effective in augmenting HIV testing rates and reaching marginalized populations compared to facility‐based testing. These strategies can be integrated with the existing HIV care services, to fill the testing gap among key populations globally. PROSPERO Number: CRD42022361782, INTRODUCTION Human immunodeficiency virus (HIV) testing is considered as a significant stage of the HIV care continuum and prevention services [1]. Knowledge of HIV status contributes to timely treatment and [...]

: Introduction: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). Methods: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase‐3 trial clinical trial in South Africa (study dates: January 2017–February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment‐emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment‐emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). Results: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0−3.4), −0.5 mmHg (95% CI: −2.2 to 1.7) and −2.1 mmHg (95% CI: −3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4–22.9), 15.4% (95% CI: 11.0–19.9) and 13.3% (95% CI: 8.9–17.6) of participants developed treatment‐emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment‐emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. Conclusions: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment‐emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. Clinical Trial Number: NCT03122262, INTRODUCTION The evolution of antiretroviral therapy in the last decade has seen the introduction of integrase‐strand transfer inhibitors (INSTIs) in fixed‐dose combinations with tenofovir prodrugs, either tenofovir disoproxil fumarate (TDF) [...]

: Introduction: To achieve epidemic control of infectious diseases, engaging higher‐burden populations with accessible diagnostic services is critical. HIV self‐testing (HIVST) is a promising option. Methods: We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self‐reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre‐determined pick‐up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow‐up services. Follow‐up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. Results: Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. Conclusions: Web‐based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder‐to‐reach populations across India. Assistance from a community‐oriented counsellor proved important to overcome literacy barriers and mistrust in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases., INTRODUCTION Globally, infectious disease programmes have ambitious targets to achieve epidemic control or elimination. UNAIDS has established 95‐95‐95 targets for HIV wherein 95% of people living with HIV (PLHIV) are [...]

A highly sensitive analytical method has been developed for trace level quantification of formaldehyde in active pharmaceutical ingredient. Formaldehyde is a highly toxic impurity. Determination of formaldehyde by using UV-visible spectroscopy is difficult due to interference of unreacted derivatizing agent; hence, either HPLC-UV or GC-MS are used for the quantification. However, we have developed an indirect method for the quantification of formaldehyde. In this method, in the first step, formaldehyde reacted with excess of 2,4-dinitrophenyl hydrazine (2,4-DNPH). In the second step, the quantification of unreacted 2,4-DNPH was done by detecting its derivative with its scavenger-cinnamaldehyde on a UV-visible spectrophotometer. The developed method is rapid, simple, sensitive and accurate for the quantification of formaldehyde. Linearity of the method was observed in the range of 0.5-3 [mu]g/mL with determination coefficients (r.sup.2) > 0.999. The limit of detection and limit of quantification are 0.25 and 0.5 [mu]g/mL, respectively., Author(s): Vidyagauri V. Lele [sup.1] Uttam Prabhanand Dalvi [sup.1] Author Affiliations: (1) grid.44871.3e, 0000 0001 0668 0201, Department of Chemistry, N.G. Acharya and D.K. Marathe College, , Chembur, 400071, Mumbai, [...]

: Introduction: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS‐related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre‐exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. Methods: This study forms part of a mixed‐methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in‐depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. Results: The final analysis included 28 heterosexual men (18–56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self‐perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily‐pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. Conclusions: Our study reports on the experiences of heterosexual men accessing oral PrEP in real‐world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access., INTRODUCTION South Africa had an estimated 7.6 million people living with HIV in 2022, of whom 2.6 million (34%) are men aged ≥15 years [1]. Despite the implementation of the [...]

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-[gamma] secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-[gamma] in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-[gamma]-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy., Introduction The influence of inflammation on various aspects of immune responses is recognized, yet the extent of these effects remains largely unknown. This is especially true within clinical contexts in [...]

Background While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged [greater than or equal to]15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with [greater than or equal to]12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality., Author(s): Ellen Brazier 1,2,*, Olga Tymejczyk 1, Kara Wools-Kaloustian 3, Awachana Jiamsakul 4, Marco Tulio Luque Torres 5, Jennifer S. Lee 6, Lisa Abuogi 7, Vohith Khol 8, Fernando Mejía [...]

SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at E6, E10, or E16 with a mouse-adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age-dependent, with greater morbidity, reduced antiviral immunity, greater viral titers, and impaired fetal growth and neurodevelopment occurring with infection at E16 (third trimester equivalent) than with infection at either E6 (first trimester equivalent) or E10 (second trimester equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir, which is recommended for individuals who are pregnant with COVID-19, we treated E16-infected dams with mouse-equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented offspring growth restriction and neurodevelopmental impairments. Our results highlight that severe COVID-19 during pregnancy and fetal growth restriction is associated with heightened virus replication in maternal lungs. Ritonavir- boosted nirmatrelvir mitigated maternal morbidity along with fetal growth and neurodevelopment restriction after SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections., Introduction Pregnancy is a risk factor for developing severe COVID-19, with individuals who are pregnant at increased risk of hospitalization, mechanical ventilation, and mortality compared with patients who are not [...]

HIV-1 persists in a latent reservoir in resting [CD4.sup.+] T cells despite antiretroviral therapy (ART). The reservoir decays slowly over the first 7 years of ART ([t.sub.1/2] = 44 months). However, whether decay continues with long-term ART is unclear. Recent integration site studies indicate gradual selection against inducible, intact proviruses, raising speculation that decades of ART might allow treatment interruption without viral rebound. Therefore, we measured the reservoir in 42 people on long-term ART (mean 22 years) using a quantitative viral outgrowth assay. After 7 years of ART, there was no long-term decrease in the frequency of inducible, replication-competent provi ruses but rather an increase with an estimated doubling time of 23 years. Another reservoir assay, the intact proviral DNA assay, confirmed that reservoir decay with [t.sub.1/2] of 44 months did not continue with long-term ART. The lack of decay reflected proliferation of infected cells. Most inducible, replication-competent viruses (79.8%) had env sequences identical to those of other isolates from the same sample. Thus, although integration site analysis indicates changes in reservoir composition, the proliferation of CD4* T cells counteracts decay, maintaining the frequency of inducible, replication-competent proviruses at roughly constant levels over the long term. These results reinforce the need for lifelong ART., Introduction Antiretroviral therapy (ART) blocks HIV-1 replication, reducing plasma virus levels to below the detection limit of clinical assays (1-3). ART prevents disease progression but does not eliminate the latent [...]