Exploring the Resurgence of a Neglected Disease: Lessons From the 2023-2024 Mpox Outbreak in Rio de Janeiro, Brazil.

Following the 2022 global mpox outbreak, diagnoses decreased worldwide, even in settings with limited vaccine access. In 2023-2024, a new outbreak emerged in Rio de Janeiro, Brazil, highlighting the importance of continuous surveillance, preventive measures such as vaccination in vulnerable populations, and treatment options, emphasizing equitable global health technology distribution.

Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case.

BACKGROUND: According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. OBJECTIVE: To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. METHODS: We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). FINDINGS: We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. MAIN CONCLUSIONS: Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.

Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug-drug interaction study in a cohort of Brazilian transgender women using HIV pre-exposure prophylaxis.

OBJECTIVES: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. METHODS: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants. RESULTS: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70-57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study. CONCLUSIONS: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.

A case report of HIV-1 superinfection in an HIV controller leading to loss of viremia control: a retrospective of 10 years of follow-up.

BACKGROUND: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. CASE PRESENTATION: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. CONCLUSIONS: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.

An Internet-Based HIV Self-Testing Program to Increase HIV Testing Uptake Among Men Who Have Sex With Men in Brazil: Descriptive Cross-Sectional Analysis.

BACKGROUND: Approximately 30% of people living with HIV worldwide are estimated to be unaware of their infection. HIV self-testing (HIVST) is a strategy recommended by the World Health Organization to increase access to and uptake of testing among key populations who are at high risk for HIV infection. OBJECTIVE: This study aimed to describe the development and feasibility of a free, anonymous, internet-based HIVST strategy designed for men who have sex with men in Curitiba, Brazil (electronic testing [e-testing]). METHODS: The project was developed under the scope of the "A Hora é Agora" (The Time is Now) program. Individuals aiming to request an HIVST package (two tests each) answered an anonymous 5-minute questionnaire regarding inclusion criteria and sexual risk behavior. Eligible individuals could receive one package every 6 months for free. Website analytics, response to online questionnaires, package distribution, and return of test results were monitored via a platform-integrated system. RESULTS: Between February 2015 and January 2016, the website documented 17,786 unique visitors and 3218 completed online questionnaires. Most individuals self-reported being white (77.0%), young (median age: 25 years, interquartile range: 22-31 years), educated (87.3% completed secondary education or more), and previously tested for HIV (62.5%). Overall, 2526 HIVST packages were delivered; of those, 542 (21.4%) reported a result online or by mail (23 reactive and 11 invalid). During the study period, 37 individuals who reported using e-testing visited the prespecified health facility for confirmatory testing (30 positive, 7 negative). CONCLUSIONS: E-testing proved highly feasible and acceptable in this study, thus supporting scale-up to additional centers for men who have sex with men in Brazil.

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control.

BACKGROUND: Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes. RESULTS: Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were < 1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (< 1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure. CONCLUSIONS: The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants.

Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

OBJECTIVES: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection. METHODS: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. RESULTS: IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. CONCLUSIONS: Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.

Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil.

BACKGROUND: Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). METHODS: The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. RESULTS: Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. CONCLUSION: Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.

Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death.

BACKGROUND: Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. METHODS: This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV" (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. RESULTS: A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). CONCLUSION: Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women.

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 µg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 µg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).

AIDS and non-AIDS severe morbidity associated with hospitalizations among HIV-infected patients in two regions with universal access to care and antiretroviral therapy, France and Brazil, 2000-2008: hospital-based cohort studies.

BACKGROUND: In high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France. METHODS: Two hospital-based cohorts of HIV-infected individuals were used for this analysis: the ANRS CO3 Aquitaine Cohort in South Western France and the Evandro Chagas Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined as all clinical diagnoses associated with a hospitalization of ≥48 hours. Trends in the incidence rate of events and their determinants were estimated while adjusting for within-subject correlation using generalized estimating equations models with an auto-regressive correlation structure and robust standard errors. RESULT: Between January 2000 and December 2008, 7812 adult patients were followed for a total of 41,668 person-years (PY) of follow-up. Throughout the study period, 90% of the patients were treated with cART. The annual incidence rate of AIDS and non-AIDS events, and of deaths significantly decreased over the years, from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to 4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events surpassed that of AIDS-events during the entire study period. High CD4 cell counts were associated with a lower incidence rate of AIDS and non-AIDS events as well as with lower rates of specific non-AIDS events, such as bacterial, hepatic, viral, neurological, and cardiovascular conditions. Adjusted analysis showed that severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs but not with setting (IPEC versus Aquitaine). CONCLUSIONS: As information on severe morbidities for HIV-infected patients remain scarce, data on hospitalizations are valuable to identify priorities for case management and to improve the quality of life of patients with a chronic disease requiring life-long treatment. Immune restoration is highly effective in reducing AIDS and non-AIDS severe morbid events irrespective of the setting.

Unprotected sex among men who have sex with men living with HIV in Brazil: a cross-sectional study in Rio de Janeiro.

BACKGROUND: Many countries are facing concentrated HIV epidemics among vulnerable populations, including men who have sex with men (MSM). Unprotected anal intercourse (UAI) is the main HIV transmission route among them and its understanding in the different cultures and how it relates to HIV transmission, re-infection and development of HIV antiretroviral resistance has important public health implications. Data on UAI among Brazilian MSM are scarce. This study aims to evaluate the prevalence and associated factors of UAI among HIV-infected MSM who had sex with seronegative or male partners with an unknown serostatus. METHOD: A cross-sectional study nested in a cohort was conducted in Rio de Janeiro, Brazil. The one hundred and fifty five MSM included in the study answered an ACASI interview and provided biological samples. Generalized linear models were used to identify variables associated with UAI. RESULTS: Overall, UAI with an HIV-negative or unknown serostatus male partner was reported by 40.6% (63/155) of MSM. Lifetime sexual abuse or domestic violence was reported by 35.9%, being more frequent among MSM who reported UAI compared to those who did not (P = 0.001). Use of stimulants before sex was reported by 20% of the MSM, being slightly higher among those who reported UAI (27.0% vs. 15.2%; P = 0.072). Commercial sex was frequent among all MSM (48.4%). After multivariate modeling, the report of sexual abuse or domestic violence (OR = 2.70; 95% CI: 1.08-7.01), commercial sex (OR = 2.28; 95% CI: 1.04- 5.10), the number of male sexual partners (p = 0.039) and exclusively receptive anal intercourse (OR = 0.21; 95% CI: 0.06-0.75) remained associated with UAI. CD4 levels, HIV viral load and antiretroviral therapy were not associated with UAI. CONCLUSION: The UAI prevalence found with negative or unknown HIV status partners points out that other interventions are needed as additional prevention tools to vulnerable MSM. The main factors associated with UAI were a lifetime history of violence, commercial sex and the number of male sexual partners. This clustering of different behavioral, health and social problems in this population reinforce the need of a comprehensive approach on treating and preventing HIV among MSM.

Monkeypox Infection Causing Conjunctival Vesicles and Anterior Uveitis.

Human monkeypox is a zoonosis caused by an orthopoxvirus and the clinical presentation resembles that of smallpox and chickenpox. The disease may start with a prodrome that includes lymphadenopathy, headache, fatigue, and fever, followed by a vesiculo-pustular rash. Ocular manifestations such as conjunctivitis and edema are present in approximately 20% of affected people, with a greater incidence among unvaccinated patients. Corneal involvement has also been reported and can result in corneal scarring and severe forms of keratitis. The natural course of the disease is most often benign and self-limiting, however, in some individuals, especially immunocompromised patients, there is a risk of complications such as bronchopneumonia, encephalitis, and vision loss. Herein, we present a case of a patient with monkeypox which caused conjunctival vesicles and anterior uveitis.

Patterns of Diversity and Humoral Immunogenicity for HIV-1 Antisense Protein (ASP).

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.

Childhood Parental Neglect, Abuse and Rejection Among Transgender Women: A Cross-Sectional Study in Rio de Janeiro, Brazil.

We aimed to estimate the proportions of childhood parental neglect, abuse, and rejection and to evaluate the co-occurrence of these experiences among transgender women in Rio de Janeiro, Brazil. This was a cross-sectional study with a convenience sample enrolled between July 2019 and March 2020, using an adapted version of the Childhood Trauma Questionnaire. Proportions and corresponding confidence intervals (CI) were calculated. Kendall correlation with Tau-b estimator was used in the bivariate analyses. We gathered data from 139 participants. The most prevalent types of childhood traumas were emotional abuse (60.43%, 95% CI [51.79, 68.62]), physical abuse (57.55%, 95% CI [48.90, 65.89]) and sexual abuse (44.60%, 95% CI [36.18, 53.27]). Severe to extreme physical and emotional abuse occurred among 40.29% (95% CI [32.06, 48.93]) and 5.75% (95% CI [2.51, 11.02]) of participants, respectively. The proportion of parental rejection (eviction) was 32.37% (95% CI [25.04, 40.69]) and occurred with the other forms of abuse, except sexual abuse. Multiple types of childhood abuse, neglect, and parental rejection were observed among transgender women in our sample. The harmful effects of childhood abuse on the mental and physical health of people in the transgender population are of concern, particularly considering the cumulative effect produced by the co-occurrence of such events and their harmful lifetime effects. It is urgently necessary to debate and formulate public policies to ensure the right to gender expression from childhood.

The first case of acute HIV and monkeypox coinfection in Latin America.

Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenital lesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.

Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review.

BACKGROUND AND OBJECTIVE: The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics. METHODS: Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18-49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432). RESULTS: Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups. CONCLUSION: Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary.

Preferences for pre-exposure prophylaxis (PrEP) among sexual and gender minorities: a discrete choice experiment in Brazil.

Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionally affected by HIV infection in Latin America. This study aims to assess pre-exposure prophylaxis (PrEP) preferences among sexual and gender minorities (SGM) and identify attributes and levels that are related to PrEP uptake and adherence, both crucial for PrEP success. Methods: We conducted a discrete choice experiment (DCE) among SGM from all Brazilian regions (September-December/2020). The survey was administered face-to-face (five Brazilian capitals) and online (entire country). We used a D-efficient zero-prior blocked experimental design to select 60 paired-profile DCE choice tasks. Findings: The total sample size was 3924 (90.5% MSM; 7.2% TGW and 2.3% non-binary or gender diverse persons). In random-effects logit models, highest levels of protection and "no side effects" were the most important attribute levels. For "presentation", injectable and implant were preferred over oral. Participants were willing to accept a 4.1% protection reduction to receive injectable PrEP or a 4.2% reduction if PrEP were taken monthly. The largest class in the latent class models was defined predominantly by the preference for the highest HIV protection level (p < 0.005). Respondents in this class also preferred no side effects, injectable and implant presentations. Interpretation: Higher HIV protection, no side effects, and presentation, whether injectable or implant, were the most important attributes in PrEP preferences. Protection against HIV was the most important attribute. PrEP programs should make available technologies such as long-acting presentations that could reunite the most desired attributes, thus maximizing acceptability and user-appropriateness. Funding: Unitaid.

Long-Acting Injectable Cabotegravir for HIV Preexposure Prophylaxis Among Sexual and Gender Minorities: Protocol for an Implementation Study.

BACKGROUND: Long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) has proven efficacious in randomized controlled trials. Further research is critical to evaluate its effectiveness in real-world settings and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs). OBJECTIVE: ImPrEP CAB Brasil is an implementation study aiming to generate critical evidence on the feasibility, acceptability, and effectiveness of incorporating CAB-LA into the existing public health oral PrEP services in 6 Brazilian cities. It will also evaluate a mobile health (mHealth) education and decision support tool, digital injection appointment reminders, and the facilitators of and barriers to integrating CAB-LA into the existing services. METHODS: This type-2 hybrid implementation-effectiveness study includes formative work, qualitative assessments, and clinical steps 1 to 4. For formative work, we will use participatory design methods to develop an initial CAB-LA implementation package and process mapping at each site to facilitate optimal client flow. SGMs aged 18 to 30 years arriving at a study clinic interested in PrEP (naive) will be invited for step 1. Individuals who tested HIV negative will receive mHealth intervention and standard of care (SOC) counseling or SOC for PrEP choice (oral or CAB-LA). Participants interested in CAB-LA will be invited for step 2, and those with undetectable HIV viral load will receive same-day CAB-LA injection and will be randomized to receive digital appointment reminders or SOC. Clinical appointments and CAB-LA injection are scheduled after 1 month and every 2 months thereafter (25-month follow-up). Participants will be invited to a 1-year follow-up to step 3 if they decide to change to oral PrEP or discontinue CAB-LA and to step 4 if diagnosed with HIV during the study. Outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. HIV incidence in the CAB-LA cohort (n=1200) will be compared with that in a similar oral PrEP cohort from the public health system. The effectiveness of the mHealth and digital interventions will be assessed using interrupted time series analysis and logistic mixed models, respectively. RESULTS: During the third and fourth quarters of 2022, we obtained regulatory approvals; programmed data entry and management systems; trained sites; and performed community consultancy and formative work. Study enrollment is programmed for the second quarter of 2023. CONCLUSIONS: ImPrEP CAB Brasil is the first study to evaluate CAB-LA PrEP implementation in Latin America, one of the regions where PrEP scale-up is most needed. This study will be fundamental to designing programmatic strategies for implementing and scaling up feasible, equitable, cost-effective, sustainable, and comprehensive alternatives for PrEP programs. It will also contribute to maximizing the impact of a public health approach to reducing HIV incidence among SGMs in Brazil and other countries in the Global South. TRIAL REGISTRATION: Clinicaltrials.gov NCT05515770; https://clinicaltrials.gov/ct2/show/NCT05515770. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44961.

Estradiol and Spironolactone Plasma Pharmacokinetics Among Brazilian Transgender Women Using HIV Pre-Exposure Prophylaxis: Analysis of Potential Interactions.

BACKGROUND AND OBJECTIVE: An important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil. METHODS: We performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]). RESULTS: Among 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]). CONCLUSION: Estradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP. TRIAL REGISTRATION: This trial (NCT03220152) was registered on July 18, 2017.