ABSTRACT Introduction: Antiretroviral therapy increased the survival and life expectancy of People living With HIV (PWH). Frailty-related syndromes among older PWH (aged 50+ years) may affect their Health-related Quality of Life (HQoL). Additionally, the COVID-19 pandemic has impacted health-related outcomes. This study aimed to estimate the prevalence of frailty and pre-frailty among older PWH, and to explore associations of HQoL with the study assessment period and frailty status. Methods: Cross-sectional study conducted pre- (23-Mar-2019 to 5-Mar-2020) and post-COVID-19 pandemic onset (23-Jun-2021 to 5-May-2022), among older PWH at INI-Fiocruz, the largest cohort of PWH in Rio de Janeiro, Brazil. We measured frailty using Fried assessment, consisting of five domains: unintentional weight loss; self-reported exhaustion, weakness, slow walking speed, low physical activity. HQoL was assessed using the ACTG SF-21, which contains 21 questions divided into 8 domains. We used Chi-Square test, Fisher’s exact test, Kruskal-Wallis and ranksum test for comparisons. Results: We included 250 older PWH: 109 (43.6 %) pre- and 141 (56.4 %) post-COVID-19 pandemic onset. Median age was 60-years (IQR: 55‒64). Most self-identified as cisgender men 152 (60.8 %), Pardo/Black 146 (58.4 %), with completed secondary education or less 181 (72.7 %) and low income 132 (52.8 %). Overall, prevalence of frailty and pre-frailty were 9.2 % (95 % CI: 8.1‒10.3) and 61.6 % (95 % CI: 54.0‒69.2). Prevalence of frailty in the pre- and pos-COVID-19 pandemic periods were 7.3 % and 10.6 % (p = 0.66). HQoL scores were lower among participants with frailty compared to those with non-frailty and pre-frailty in all eight domains, and among those included in the post-COVID-19 compared to pre-COVID-19 period for four domains. Conclusions: We observed low prevalence of frailty, but high prevalence of pre-frailty among older PWH. Frailty status did not differ according to the COVID-19 assessment period. Assessment of frailty and HQoL should be incorporated in clinical practice for older PWH. Programs to reverse or prevent frailty should be implemented within the public health system. Introduction . (PWH) Frailtyrelated related aged 50 years Healthrelated Health HQoL. (HQoL) Additionally COVID19 COVID 19 COVID-1 healthrelated outcomes prefrailty pre Methods Crosssectional Cross sectional 23Mar2019 Mar 23 2019 (23-Mar-201 5Mar2020 5 2020 5-Mar-2020 postCOVID19 postCOVID post post-COVID-1 23Jun2021 Jun 2021 (23-Jun-202 5May2022, 5May2022 May 2022 , 5-May-2022) INIFiocruz, INIFiocruz INI Fiocruz, Fiocruz INI-Fiocruz Janeiro Brazil domains loss selfreported self reported exhaustion weakness speed activity SF21, SF21 SF 21, SF-21 2 ChiSquare Chi Square Fishers Fisher s KruskalWallis Kruskal Wallis comparisons Results 25 10 43.6 436 43 6 (43. 14 56.4 564 56 4 (56. 60years 60 IQR (IQR 55‒64. 5564 55‒64 55 64 55‒64) selfidentified identified 15 60.8 608 (60. %, PardoBlack Pardo Black 58.4 584 58 (58. 18 72.7 727 72 7 (72. 13 52.8 528 52 (52. %. Overall 92 9 9. 95 (9 CI 8.1‒10.3 81103 1 3 616 61 61. 54.0‒69.2. 540692 54.0‒69.2 54 0 69 54.0‒69.2) posCOVID19 posCOVID pos pos-COVID-1 73 7. 106 10. p 0.66. 066 0.66 66 0.66) nonfrailty non preCOVID19 preCOVID pre-COVID-1 Conclusions system (PWH (HQoL COVID1 COVID- 23Mar201 201 (23-Mar-20 5Mar202 202 5-Mar-202 postCOVID1 post-COVID- 23Jun202 (23-Jun-20 5May202 5-May-2022 SF2 SF-2 43. (43 56. (56 556 55‒6 60. (60 58. (58 72. (72 52. (52 ( 8.1‒10. 8110 54069 54.0‒69. posCOVID1 pos-COVID- 06 0.6 preCOVID1 pre-COVID- 23Mar20 20 (23-Mar-2 5Mar20 5-Mar-20 post-COVID 23Jun20 (23-Jun-2 5May20 5-May-202 SF- (4 (5 55‒ (6 (7 8.1‒10 811 5406 54.0‒69 pos-COVID 0. pre-COVID 23Mar2 (23-Mar- 5Mar2 5-Mar-2 23Jun2 (23-Jun- 5May2 5-May-20 8.1‒1 81 540 54.0‒6 23Mar (23-Mar 5Mar 5-Mar- 23Jun (23-Jun 5May 5-May-2 8.1‒ 54.0‒ 5-Mar 5-May- 8.1 54.0 5-May 8. 54.

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination. Background DD (PLWH limited postvaccination post HIVuninfected uninfected [HIV(- . controls] Methods NCT03132311 NCT (NCT03132311 HIV(- 3 36 Janeiro Brazil obtained throughrealtime throughreal time units assays, assays , assays) neutrophils, (neutrophils AST postvaccination. Results 20 CD cellsμL cells μL 6 analyses 0 20. 22.8% 228 22 8 (22.8 vs 118 11 11. pvalue p value 0.001. 0001 0.001 001 0.001) Neutrophils Conclusions welltolerated well tolerated Postvaccination Post selflimited self [HIV( NCT0313231 (NCT0313231 HIV( 2 22.8 (22. 1 000 0.00 00 [HIV NCT031323 (NCT031323 22. (22 0.0 NCT03132 (NCT03132 (2 0. NCT0313 (NCT0313 ( NCT031 (NCT031 NCT03 (NCT03 NCT0 (NCT0 (NCT

Abstract Introduction In Brazil, though Antiretroviral Therapy (ART) is available to all, the benefits may not be experienced uniformly. We projected Life Expectancy (LE) for People Living with HIV (PLHIV) in care as currently observed and estimated the impact of guideline-concordant care. Methods Using a microsimulation model, we projected LE for a cohort of PLHIV and for four population groups: cisgender Men who have Sex with Men (MSM), cisgender Men who have Sex with Women (MSW), Cisgender Women (CGW), and Transgender Women (TGW). Cohort data from Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation (INI/Fiocruz) informed model parameters. We modeled five scenarios: 1) Current care: ART initiation, adherence, and retention in care as currently observed, 2) Guideline-concordant care: immediate ART initiation, full adherence to treatment, and consistent retention in care, 3) Immediate ART initiation with observed adherence to treatment and retention in care, 4) Full adherence to treatment with observed timing of ART initiation and retention in care, and 5) Consistent retention in care with observed timing of ART initiation and adherence. Results With current care, LE from age 15 would be 45.9, 44.4, 54.2, and 42.3 years, for MSM, MSW, CGW, and TGW. With guideline-concordant care, LE would be 54.2, 54.4, 63.1, and 53.2 years, for MSM, MSW, CGW and TGW, with TGW experiencing the greatest potential increase in LE (10.9 years). When investigating the components of care separately, MSW and CGW would gain most LE with immediate ART initiation, whereas for MSM and TGW consistent retention in care would be most impactful. Conclusions In settings like INI/Fiocruz, MSW and CGW would benefit most from interventions focused on earlier diagnosis and linkage to care, whereas TGW and MSM would benefit from interventions to sustain engagement in care. Assessment of the HIV care continuum for specific populations should inform care priorities. Brazil (ART all uniformly (LE (PLHIV guidelineconcordant guideline concordant groups , (MSM) (MSW) (CGW) . (TGW) DiseasesOswaldo Diseases Oswaldo INI/Fiocruz INIFiocruz INI Fiocruz (INI/Fiocruz parameters scenarios 1 2 Guidelineconcordant Guideline 3 4 5 459 45 9 45.9 444 44 44.4 542 54 54.2 423 42 42. years 544 54.4 631 63 63.1 532 53 53. 10.9 109 10 (10. years. years) separately impactful priorities (MSM (MSW (CGW (TGW 45. 44. 54. 6 63. 10. (10 (1 (

BACKGROUND Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. OBJECTIVES To understand the ability of HICs to control the expression of endogenous retroviruses. METHODS We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. FINDINGS Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. MAIN CONCLUSIONS These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions. HIV1 1 (HIV)- HERVs, HERVs , (HERVs) HERVK HERV K HML2. HML2 HML 2 . (HML-2) (HICs PLWHs (PLWHs HIV- LTRdriven LTR driven proviruses ERVK6 ERVK 6 (ERVK-6 (PBMCs n 23, 23 23) ARTsuppressed suppressed 8, 8 8) HIV1negative HIVnegative negative (NEG 10 ERVK- Moreover p p2 MCPIP NFkB. NFkB NF kB. kB NF-kB (HIV-1 conditions (HIV) (HERVs (HML-2 (ERVK- (HIV- (HIV (HML- (ERVK (HML

ABSTRACT Background: This study aimed to identify COVID-19 cases among people living with HIV (PLWH) in Brazil in 2020, describe their clinical, sociodemographic, and epidemiological profiles, and evaluate the factors associated with disease severity. Methods: This cross-sectional study used secondary data obtained from the Brazilian healthcare system. Probabilistic and deterministic data linkage methods were used to identify coinfected patients. Descriptive statistical analysis was conducted, and factors associated with severe cases were evaluated using Pearson's chi-squared test, Student's t-test, and logistic regression. Results: In 2020, 36,746 coinfections were identified, making it one of the largest coinfection databases described worldwide. In total, 4,502 (12.25%) patients had severe cases and 32,244 (87.75%) had non-severe cases. The covariates age (OR=1.05; 95% CI: 1.05-1.06), nonwhite ethnicity (OR=1.68; 95% CI: 1.56-1.81), history of AIDS diagnosis (OR=1.17; 95% CI: 1.08-1.28), recent HIV diagnosis (OR=5.47; 95% CI: 4.25-7.02), absence of antiretroviral therapy (OR=1.70; 95% CI: 1.57-1.84), CD4+ < 200 (OR=6.41; 95% CI: 5.09-8.08), detectable HIV viral load (OR=2.61; 95% CI: 2.21-3.05), ≥ 1 comorbidity (OR=4.09; 95% CI: 3.79-4.41), and ≥ 4 symptoms were associated with increased severity. Conclusions: Multiple factors were linked to severe COVID-19, including uncontrolled HIV infection, age > 50 years, comorbidities, and racial disparities. This study reinforces the importance of maintaining public policies focused on early HIV diagnosis, access and adherence to treatment, especially for minority ethnic groups, and focusing on premature aging in PLWH. Background COVID19 COVID 19 COVID-1 PLWH (PLWH 2020 clinical sociodemographic profiles severity Methods crosssectional cross sectional system conducted Pearsons Pearson s chisquared chi squared test Students Student ttest, ttest t t-test regression Results 36746 36 746 36,74 identified worldwide total 4502 502 4,50 12.25% 1225 12 25 (12.25% 32244 32 244 32,24 87.75% 8775 87 75 (87.75% nonsevere non OR=1.05 OR105 OR 05 (OR=1.05 95 CI 1.051.06, 105106 1.05 1.06 , 06 1.05-1.06) OR=1.68 OR168 68 (OR=1.68 1.561.81, 156181 1.56 1.81 56 81 1.56-1.81) OR=1.17 OR117 17 (OR=1.17 1.081.28, 108128 1.08 1.28 08 28 1.08-1.28) OR=5.47 OR547 5 47 (OR=5.47 4.257.02, 425702 4.25 7.02 7 02 4.25-7.02) OR=1.70 OR170 70 (OR=1.70 1.571.84, 157184 1.57 1.84 57 84 1.57-1.84) CD4 CD 20 OR=6.41 OR641 6 41 (OR=6.41 5.098.08, 509808 5.09 8.08 09 8 5.09-8.08) OR=2.61 OR261 2 61 (OR=2.61 2.213.05, 221305 2.21 3.05 21 3 2.21-3.05) OR=4.09 OR409 (OR=4.09 3.794.41, 379441 3.79 4.41 79 3.79-4.41) Conclusions COVID19, 19, infection years comorbidities disparities treatment groups COVID1 COVID- 202 3674 74 36,7 450 4,5 12.25 122 (12.25 3224 24 32,2 87.75 877 (87.75 OR=1.0 OR10 0 (OR=1.0 9 051 1.051.06 10510 105 1.0 106 1.05-1.06 OR=1.6 OR16 (OR=1.6 561 1.561.81 15618 156 1.5 181 1.8 1.56-1.81 OR=1.1 OR11 (OR=1.1 081 1.081.28 10812 108 128 1.2 1.08-1.28 OR=5.4 OR54 (OR=5.4 257 4.257.02 42570 425 4.2 702 7.0 4.25-7.02 OR=1.7 OR17 (OR=1.7 571 1.571.84 15718 157 184 1.57-1.84 OR=6.4 OR64 (OR=6.4 098 5.098.08 50980 509 5.0 808 8.0 5.09-8.08 OR=2.6 OR26 (OR=2.6 213 2.213.05 22130 221 2.2 305 3.0 2.21-3.05 OR=4.0 OR40 (OR=4.0 794 3.794.41 37944 379 3.7 441 4.4 3.79-4.41 367 36, 45 4, 12.2 (12.2 322 32, 87.7 (87.7 OR=1. OR1 (OR=1. 1.051.0 1051 10 1. 1.05-1.0 1.561.8 1561 15 18 1.56-1.8 1.081.2 1081 1.08-1.2 OR=5. OR5 (OR=5. 4.257.0 4257 42 4. 7. 4.25-7.0 1.571.8 1571 1.57-1.8 OR=6. OR6 (OR=6. 5.098.0 5098 5. 80 8. 5.09-8.0 OR=2. OR2 (OR=2. 2.213.0 2213 22 2. 30 3. 2.21-3.0 OR=4. OR4 (OR=4. 3.794.4 3794 37 44 3.79-4.4 12. (12. 87. (87. OR=1 (OR=1 1.051. 1.05-1. 1.561. 1.56-1. 1.081. 1.08-1. OR=5 (OR=5 4.257. 4.25-7. 1.571. 1.57-1. OR=6 (OR=6 5.098. 5.09-8. OR=2 (OR=2 2.213. 2.21-3. OR=4 (OR=4 3.794. 3.79-4. (12 (87 OR= (OR= 1.051 1.05-1 1.561 1.56-1 1.081 1.08-1 4.257 4.25-7 1.571 1.57-1 5.098 5.09-8 2.213 2.21-3 3.794 3.79-4 (1 (8 (OR 1.05- 1.56- 1.08- 4.25- 1.57- 5.09- 2.21- 3.79- (

BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir’s reseeding and low, but measurable, viral evolution despite undetectable viremia. (EC HIVpositive positive characteristics HIV1 1 HIV- CD4 CD cells However PBMCassociated PBMC associated reservoirs intrahost intra host PBMCsassociated PBMCs mean 1.94.1% 1941 1.9 4.1% 9 4 1.9-4.1% timepoints pressure population longterm long term s measurable viremia 94 1.94.1 194 19 1. 41 4.1 1.9-4.1 1.94. 4. 1.9-4. 1.94 1.9-4 1.9-

ABSTRACT 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 anogenitallesions, 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. (MPX nonendemic non endemic 2022 multicountry multi country outbreak dynamics anogenitallesions cases STIs (STIs America course initiated investigation 202 20 2

ABSTRACT Background: Antiretroviral therapy use has led to a decline in HIV-related mortality yet disparities by gender and/or sexual orientation may exist. In this study, we estimated hazards of death in people living with HIV (PLWH) according to gender and sexual orientation. Methods: We included PLWH ≥ 18 years enrolled between 2000 and 2018 at INI/Fiocruz, Rio de Janeiro, Brazil. Participants were grouped as cisgender or transgender women, cisgender men who have sex with men (MSM) or men who have sex with women, or cisgender men with unknown sexual orientation. We assessed disparities in the hazard of death using Cox proportional hazards models. Results: Among 5,576 PLWH, median age at enrollment was 35 years, 39% were MSM, 28% cisgender women, 23% men who have sex with women, 5% transgender women, and 5% men with unknown sexual orientation. A total of 795 deaths occurred in 39,141 person-years of follow-up. Mortality rates per 1,000 person-years were: 82.4 for men with unknown sexual orientation, 24.5 for men who have sex with women, 18.3 for cisgender, 16.6 for transgender women, and 15.1 for MSM. Compared to MSM, men with unknown sexual orientation had the highest death hazard ratio (adjusted hazard ratio [aHR] 2.93, 95% confidence interval [CI] 2.35–3.81), followed by men who have sex with women (aHR 1.17, 95%CI 0.96, 1.43); death hazard ratios for cisgender and transgender women were not statistically different. Conclusion: We observed disparities in the hazard of death for men with unknown sexual orientation and men who have sex with women despite universal access to antiretroviral therapy in Brazil. Future work should characterize and assist men with unknown sexual orientation with tailored policies and interventions. Increased hazard of death was not observed for transgender women, which probably results from interventions implemented in our service to reach, engage, retain, and support this population. Background HIVrelated related andor exist study (PLWH Methods 1 200 201 INIFiocruz INI Fiocruz INI/Fiocruz Janeiro Brazil MSM (MSM models Results 5576 5 576 5,57 3 39 28 23 79 39141 141 39,14 personyears person followup. followup follow up. up follow-up 1000 000 1,00 824 82 4 82. 245 24 24. 183 18. 166 16 6 16. 151 15 15. adjusted aHR [aHR 293 2 93 2.93 95 CI [CI 2.35–3.81, 235381 2.35–3.81 , 81 2.35–3.81) 117 17 1.17 95CI 096 0 96 0.96 1.43 143 43 1.43) different Conclusion reach engage retain population 20 557 57 5,5 7 3914 14 39,1 100 00 1,0 8 29 9 2.9 23538 2.35–3.8 11 1.1 09 0.9 1.4 55 5, 391 39, 10 1, 2. 2353 2.35–3. 1. 0. 235 2.35–3 2.35– 2.35 2.3

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. 202 (Mpox CDC, CDC , (CDC) 10 outbreak providers provider s PFU (PFU assay RTPCR RT PCR (RT-PCR TEM . (TEM) properties 20 (CDC 1 (TEM 2

Resumen El objetivo de este estudio fue analizar la incidencia del embarazo y los factores asociados en una cohorte de mujeres que viven con VIH/SIDA (MVHA) en Río de Janeiro, Brasil. Se realizó una cohorte clínica con 753 MVHA entre 1996 y 2016. Las mujeres de 18-49 años que no estaban en la menopausia natural o quirúrgica y que no tenían ligadura de trompas fueron elegibles para el estudio. Los datos se recopilaron durante las consultas iniciales y de seguimiento por parte de profesionales médicos. Las tasas de incidencia por persona-tiempo se calcularon durante todo el período de seguimiento. Se realizaron análisis univariados y múltiples para investigar los factores asociados con la incidencia del embarazo utilizando una extensión del modelo de supervivencia de Cox. Se registraron 194 embarazos durante las consultas de seguimiento, con una tasa de incidencia de 4,01/100 personas-año (IC95%: 3,47-4,60). Una mayor incidencia de embarazo se asoció con nadir CD4 ≥ 350 células/mm3, terapia antirretroviral sin Efavirenz y embarazo previo en la adolescencia, mientras que una menor incidencia se observó en mujeres con carga viral ≥ 50 copias/mL, edad ≥ 35 años, con dos o más hijos y que usaban un método anticonceptivo muy eficaz. Hubo una reducción significativa en la incidencia de embarazos después de 2006, una reducción significativa en la esterilización femenina entre 1996 y 2016 y una alta tasa de cesáreas. La asociación entre la incidencia de embarazos y el uso de métodos anticonceptivos y marcadores de control virológico sugiere una buena integración entre el VIH/SIDA y los servicios de salud reproductiva. La alta tasa de cesáreas indica la necesidad de mejorar la asistencia al parto. VIHSIDA VIH SIDA (MVHA Janeiro Brasil 75 199 1849 18 49 18-4 médicos personatiempo persona tiempo Cox 19 401100 4 01 100 4,01/10 personasaño personas año IC95% IC95 IC (IC95% 3,474,60. 347460 3,47 4,60 . 3 47 60 3,47-4,60) CD célulasmm3 célulasmm células mm3 mm células/mm3 adolescencia 5 copiasmL copias mL copias/mL eficaz 2006 201 reproductiva parto 7 184 1 18- 40110 0 10 4,01/1 IC9 (IC95 474 3,474,60 34746 347 3,4 460 4,6 6 3,47-4,60 células/mm 200 20 4011 4,01/ (IC9 3,474,6 3474 34 3, 46 4, 3,47-4,6 2 401 4,01 (IC 3,474, 3,47-4, 40 4,0 3,474 3,47-4 3,47-

Resumo O objetivo deste estudo foi analisar a incidência de gravidez e fatores associados em uma coorte de mulheres vivendo com HIV/aids (MVHA) no Rio de Janeiro, Brasil. Foi realizada uma coorte clínica com 753 MVHA entre 1996 e 2016. Mulheres com idade entre 18-49 anos que não estavam na menopausa natural ou cirúrgica e que não tinham laqueadura tubária foram elegíveis para o estudo. Os dados foram coletados durante as consultas iniciais e de acompanhamento por profissionais médicos. As taxas de incidência por pessoa-tempo foram calculadas durante todo o período de acompanhamento. Análises univariadas e múltiplas foram realizadas para investigar fatores associados à incidência de gravidez, utilizando uma extensão do modelo de sobrevida de Cox. Foram registradas 194 gestações durante as consultas de acompanhamento, com uma taxa de incidência de 4,01/100 pessoas-ano (IC95%: 3,47-4,60). Uma maior incidência de gravidez foi associada a nadir CD4 ≥ 350 células/mm³, terapia antirretroviral sem Efavirenz e gravidez anterior na adolescência, enquanto uma menor incidência foi observada em mulheres com carga viral ≥ 50 cópias/mL, idade ≥ 35 anos, com dois ou mais filhos e que usavam um método contraceptivo altamente eficaz. Houve uma redução significativa na incidência de gestações após 2006, uma redução significativa na esterilização feminina entre 1996 e 2016 e uma alta taxa de cesarianas. A associação entre a incidência de gestações e o uso de métodos contraceptivos e marcadores de controle virológico sugere uma boa integração entre HIV/aids e serviços de saúde reprodutiva. A alta taxa de cesarianas indica a necessidade de melhoria na assistência ao parto. HIVaids HIV aids (MVHA Janeiro Brasil 75 199 1849 18 49 18-4 médicos pessoatempo pessoa tempo Cox 19 401100 4 01 100 4,01/10 pessoasano pessoas ano IC95% IC95 IC (IC95% 3,474,60. 347460 3,47 4,60 . 3 47 60 3,47-4,60) CD célulasmm³ célulasmm células mm³ mm células/mm³ adolescência 5 cópiasmL cópias mL cópias/mL eficaz 2006 201 reprodutiva parto 7 184 1 18- 40110 0 10 4,01/1 IC9 (IC95 474 3,474,60 34746 347 3,4 460 4,6 6 3,47-4,60 células/mm 200 20 4011 4,01/ (IC9 3,474,6 3474 34 3, 46 4, 3,47-4,6 2 401 4,01 (IC 3,474, 3,47-4, 40 4,0 3,474 3,47-4 3,47-

Abstract The aim of this research was to analyze pregnancy incidence and associated factors in a cohort of 753 women living with HIV/AIDS (WLWHA) in Rio de Janeiro, Brazil, from 1996 to 2016. Women aged 18-49 years who were not on menopause (surgical or natural) and did not have a tubal ligation were eligible for the study. Data were collected by medical professionals during initial and follow-up visits. Person-time pregnancy incidence rates were calculated throughout the follow-up period. Pregnancy incidence-associated factors were investigated by univariate and multiple analyzes, using an extension of the Cox survival model. Follow-up visits recorded 194 pregnancies, with an incidence rate of 4.01/100 person-years (95% CI: 3.47; 4.60). A higher pregnancy incidence was associated with CD4 nadir ≥ 350 cells/mm³, use of an antiretroviral regimen not containing Efavirenz, and prior teenage pregnancy. In turn, women with a viral load ≥ 50 copies/mL, age ≥ 35 years old, with two or more children and using a highly effective contraceptive method showed a lower incidence. Results showed a significant reduction in pregnancy incidence after 2006, a significant reduction in female sterilization from 1996 to 2016, and a high rate of cesarean sections. The association found between pregnancy incidence and the use of contraceptive methods and virological control markers suggests a good integration between HIV/AIDS and reproductive health services. The high rate of cesarean section delivery indicates the need to improve childbirth care. 75 HIVAIDS HIV AIDS WLWHA (WLWHA Janeiro Brazil 199 2016 1849 18 49 18-4 surgical natural study followup follow up Persontime Person time period incidenceassociated analyzes model Followup Follow 19 pregnancies 401100 4 01 100 4.01/10 personyears person 95% 95 (95 CI 3.47 347 3 47 4.60. 460 4.60 . 60 4.60) CD cellsmm³ cellsmm cells mm³ mm cells/mm³ Efavirenz turn 5 copiesmL copies mL copies/mL old 2006 sections services care 7 201 184 1 18- 40110 0 10 4.01/1 9 (9 3.4 34 46 4.6 6 cells/mm 200 20 4011 4.01/ ( 3. 4. 2 401 4.01 40 4.0

Resumo O artigo descreve a estimação dos custos potenciais, sob a ótica do Ministério da Saúde (MS), da implementação do medicamento cabotegravir injetável de longa duração (CAB LA) no Sistema Único de Saúde, como alternativa para a prevenção à infecção pelo HIV e parte da estratégia nacional de prevenção combinada. Utilizou-se o instrumental analítico de cadeias de valor para elaborar a cadeia de valor do CAB LA com a identificação dos seus elos e atividades. Foram definidos três cenários de demanda com base em dados da população-alvo, variando em abrangência geográfica, e calculados os custos potenciais. A cadeia de valor do CAB LA é dividida em três grandes elos: produção, incorporação e assistência farmacêutica. Somente o último é considerado para o cálculo dos custos sob responsabilidade orçamentária do MS. Os custos potenciais são estimados em R$ 15 milhões, R$ 19 milhões e R$ 21,8 milhões, nos cenários de demanda baixa, média e alta, respectivamente. O estudo apresenta os custos potenciais para o MS, incluindo a necessidade de testes e procedimentos, de forma a orientar os gestores públicos e o próprio processo de incorporação. A ausência de preço do CAB LA é uma importante limitação para os resultados. MS , (MS) combinada Utilizouse Utilizou se atividades populaçãoalvo, populaçãoalvo população alvo, alvo população-alvo geográfica produção farmacêutica R 1 218 21 8 21, baixa alta respectivamente procedimentos resultados (MS 2

Abstract The article describes the estimation of the potential costs, from the perspective of the Ministry of Health (MoH), of incorporating the long-acting injectable cabotegravir (CAB LA) within the Brazilian Unified Health System, as an alternative for the prevention of HIV infection and part of the national combination prevention strategy. The analytical tools of value chains were used to elaborate the CAB LA value chain by identifying its links and activities. Three demand scenarios were defined based on target population data, varying geographic scope, and potential costs were calculated. CAB LA's value chain is divided into three major links: production, incorporation, and pharmaceutical assistance. Only the latter is considered for the calculation of costs under the budgetary responsibility of the MoH. Potential costs are estimated at R$15 million, R$19 million and R$21.8 million, in low, medium, and high demand scenarios, respectively. The study presents the potential costs for the MoH, including the need for tests and procedures, to guide public managers and the incorporation process. The lack of price for CAB LA is an important limitation of the results. MoH , (MoH) longacting long acting System strategy activities data scope calculated LAs s production assistance R15 R 15 R$1 R19 19 R218 21 8 R$21. low medium respectively procedures process results (MoH R1 1 R$ R21 2 R$21 R2 R$2

ABSTRACT Syndemic psychosocial and reproductive factors affecting women’s retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000–2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced > 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women’s retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies. womens s understudied nonretention non 20002015 2000 2015 2000–2015 selfreported self reported physicalsexual physical sexual conditions range 4, 4 , 4) nonretention, retention, CD enrollment 91 18 18% 53.2%, 532 53.2% 53 (53.2%) 38.3%, 383 38.3% 38 (38.3%) 27.3%, 273 27.3% 27 (27.3%) 17.2% 172 17 (17.2%) 412 41 41.2 education syphilis studies 2000201 200 201 2000–201 9 1 53.2 5 (53.2% 38.3 (38.3% 27.3 (27.3% 17.2 (17.2% 41. 200020 20 2000–20 53. (53.2 38. (38.3 27. (27.3 17. (17.2 20002 2000–2 (53. (38. (27. (17. 2000– (53 (38 (27 (17 (5 (3 (2 (1 (

Abstract Introduction Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (FTC/TDF) is highly effective in preventing HIV infection. This study aimed to identify factors associated with PrEP early loss to follow-up (ELFU) among gay, bisexual and other men who have sex with men (MSM), travestis and transgender women (TGW). Methodology This was a prospective cohort study evaluating TGW and MSM who initiated PrEP at the Evandro Chagas National Institute of Infectious Diseases (INI-Fiocruz) from 2014 to 2020. ELFU was defined as not returning for a PrEP visit within 180 days after first dispensation. Exposure variables included age, gender, race, education, transactional sex, condomless anal intercourse [CAI] (both in the past six months), binge drinking and substance use (both in past three months) and syphilis diagnosis at baseline. Multilevel logistic regression models with random intercepts and fixed slopes were used to identify factors associated with ELFU accounting for clustering of participants according to their PrEP initiation study/context (PrEP Brasil, PrEParadas, ImPrEP and PrEP SUS). Results Among 1,463 participants, the median age was 29 years (interquartile range 24-36), 83% self-identified as MSM, 17% as TGW, 24% were black, 37% mixed-black/pardo and 30% had < 12 years of education. Fifteen percent reported transactional sex, 59% reported CAI, 67% binge drinking, 33% substance use, and 15% had a syphilis diagnosis. Overall, 137 participants (9.7%) had ELFU. Younger age (18-24 years) (adjusted odds ratio [aOR] 1.9, 95%CI:1.2-3.2), TGW (aOR 2.8, 95%CI:1.6-4.8) and education < 12 years (aOR 1.9, 95%CI:1.2-2.9) were associated with greater odds of ELFU. Conclusion TGW, young individuals and those with lower education were at higher risk of PrEP ELFU. Our results suggest that the development of specific strategies targeting these populations should be a priority, through policies that aim to reduce the incidence of HIV infection. preexposure pre exposure emtricitabinetenofovir emtricitabine tenofovir FTC/TDF FTCTDF FTC TDF (FTC/TDF infection followup follow up (ELFU gay , (MSM) TGW. . (TGW) INIFiocruz INI Fiocruz (INI-Fiocruz 201 2020 18 dispensation gender race CAI [CAI both months, months baseline studycontext context Brasil PrEParadas SUS. SUS SUS) 1463 1 463 1,46 2 interquartile 2436, 2436 24 36 24-36) 83 selfidentified self identified 17 black 37 mixedblack/pardo mixedblackpardo mixed black/pardo pardo 30 59 67 33 15 Overall 13 9.7% 97 9 7 (9.7% 1824 (18-2 adjusted aOR [aOR 19 1.9 95%CI1.23.2, 95CI1232 CI 95%CI 1.2 3.2 95 3 95%CI:1.2-3.2) 28 8 2.8 95%CI1.64.8 95CI1648 1.6 4.8 6 4 95%CI:1.6-4.8 95%CI1.22.9 95CI1229 2.9 95%CI:1.2-2.9 priority (MSM (TGW 20 202 146 46 1,4 243 24-36 mixedblack blackpardo 5 9.7 (9.7 182 (18- 1. CI1 23 95%CI1.23.2 95CI123 95CI 32 3. 95%CI:1.2-3.2 2. 64 95%CI1.64. 95CI164 16 48 4. 95%CI:1.6-4. 22 95%CI1.22. 95CI122 95%CI:1.2-2. 14 1, 24-3 9. (9. (18 95%CI1.23. 95CI12 95%CI:1.2-3. 95%CI1.64 95CI16 95%CI:1.6-4 95%CI1.22 95%CI:1.2-2 24- (9 (1 95%CI1.23 95CI1 95%CI:1.2-3 95%CI1.6 95%CI:1.6- 95%CI1.2 95%CI:1.2- ( 95%CI1. 95%CI:1.6 95%CI:1.2 95%CI1 95%CI:1. 95%CI:1 95%CI:

Resumo O objetivo deste estudo foi analisar a incidência de gravidez e fatores associados em uma coorte de mulheres vivendo com HIV/aids (MVHA) no Rio de Janeiro, Brasil. Foi realizada uma coorte clínica com 753 MVHA entre 1996 e 2016. Mulheres com idade entre 18-49 anos que não estavam na menopausa natural ou cirúrgica e que não tinham laqueadura tubária foram elegíveis para o estudo. Os dados foram coletados durante as consultas iniciais e de acompanhamento por profissionais médicos. As taxas de incidência por pessoa-tempo foram calculadas durante todo o período de acompanhamento. Análises univariadas e múltiplas foram realizadas para investigar fatores associados à incidência de gravidez, utilizando uma extensão do modelo de sobrevida de Cox. Foram registradas 194 gestações durante as consultas de acompanhamento, com uma taxa de incidência de 4,01/100 pessoas-ano (IC95%: 3,47-4,60). Uma maior incidência de gravidez foi associada a nadir CD4 ≥ 350 células/mm³, terapia antirretroviral sem Efavirenz e gravidez anterior na adolescência, enquanto uma menor incidência foi observada em mulheres com carga viral ≥ 50 cópias/mL, idade ≥ 35 anos, com dois ou mais filhos e que usavam um método contraceptivo altamente eficaz. Houve uma redução significativa na incidência de gestações após 2006, uma redução significativa na esterilização feminina entre 1996 e 2016 e uma alta taxa de cesarianas. A associação entre a incidência de gestações e o uso de métodos contraceptivos e marcadores de controle virológico sugere uma boa integração entre HIV/aids e serviços de saúde reprodutiva. A alta taxa de cesarianas indica a necessidade de melhoria na assistência ao parto.

Resumen El objetivo de este estudio fue analizar la incidencia del embarazo y los factores asociados en una cohorte de mujeres que viven con VIH/SIDA (MVHA) en Río de Janeiro, Brasil. Se realizó una cohorte clínica con 753 MVHA entre 1996 y 2016. Las mujeres de 18-49 años que no estaban en la menopausia natural o quirúrgica y que no tenían ligadura de trompas fueron elegibles para el estudio. Los datos se recopilaron durante las consultas iniciales y de seguimiento por parte de profesionales médicos. Las tasas de incidencia por persona-tiempo se calcularon durante todo el período de seguimiento. Se realizaron análisis univariados y múltiples para investigar los factores asociados con la incidencia del embarazo utilizando una extensión del modelo de supervivencia de Cox. Se registraron 194 embarazos durante las consultas de seguimiento, con una tasa de incidencia de 4,01/100 personas-año (IC95%: 3,47-4,60). Una mayor incidencia de embarazo se asoció con nadir CD4 ≥ 350 células/mm3, terapia antirretroviral sin Efavirenz y embarazo previo en la adolescencia, mientras que una menor incidencia se observó en mujeres con carga viral ≥ 50 copias/mL, edad ≥ 35 años, con dos o más hijos y que usaban un método anticonceptivo muy eficaz. Hubo una reducción significativa en la incidencia de embarazos después de 2006, una reducción significativa en la esterilización femenina entre 1996 y 2016 y una alta tasa de cesáreas. La asociación entre la incidencia de embarazos y el uso de métodos anticonceptivos y marcadores de control virológico sugiere una buena integración entre el VIH/SIDA y los servicios de salud reproductiva. La alta tasa de cesáreas indica la necesidad de mejorar la asistencia al parto.

Abstract The aim of this research was to analyze pregnancy incidence and associated factors in a cohort of 753 women living with HIV/AIDS (WLWHA) in Rio de Janeiro, Brazil, from 1996 to 2016. Women aged 18-49 years who were not on menopause (surgical or natural) and did not have a tubal ligation were eligible for the study. Data were collected by medical professionals during initial and follow-up visits. Person-time pregnancy incidence rates were calculated throughout the follow-up period. Pregnancy incidence-associated factors were investigated by univariate and multiple analyzes, using an extension of the Cox survival model. Follow-up visits recorded 194 pregnancies, with an incidence rate of 4.01/100 person-years (95% CI: 3.47; 4.60). A higher pregnancy incidence was associated with CD4 nadir ≥ 350 cells/mm³, use of an antiretroviral regimen not containing Efavirenz, and prior teenage pregnancy. In turn, women with a viral load ≥ 50 copies/mL, age ≥ 35 years old, with two or more children and using a highly effective contraceptive method showed a lower incidence. Results showed a significant reduction in pregnancy incidence after 2006, a significant reduction in female sterilization from 1996 to 2016, and a high rate of cesarean sections. The association found between pregnancy incidence and the use of contraceptive methods and virological control markers suggests a good integration between HIV/AIDS and reproductive health services. The high rate of cesarean section delivery indicates the need to improve childbirth care.

Resumo O artigo descreve a estimação dos custos potenciais, sob a ótica do Ministério da Saúde (MS), da implementação do medicamento cabotegravir injetável de longa duração (CAB LA) no Sistema Único de Saúde, como alternativa para a prevenção à infecção pelo HIV e parte da estratégia nacional de prevenção combinada. Utilizou-se o instrumental analítico de cadeias de valor para elaborar a cadeia de valor do CAB LA com a identificação dos seus elos e atividades. Foram definidos três cenários de demanda com base em dados da população-alvo, variando em abrangência geográfica, e calculados os custos potenciais. A cadeia de valor do CAB LA é dividida em três grandes elos: produção, incorporação e assistência farmacêutica. Somente o último é considerado para o cálculo dos custos sob responsabilidade orçamentária do MS. Os custos potenciais são estimados em R$ 15 milhões, R$ 19 milhões e R$ 21,8 milhões, nos cenários de demanda baixa, média e alta, respectivamente. O estudo apresenta os custos potenciais para o MS, incluindo a necessidade de testes e procedimentos, de forma a orientar os gestores públicos e o próprio processo de incorporação. A ausência de preço do CAB LA é uma importante limitação para os resultados.

Abstract The article describes the estimation of the potential costs, from the perspective of the Ministry of Health (MoH), of incorporating the long-acting injectable cabotegravir (CAB LA) within the Brazilian Unified Health System, as an alternative for the prevention of HIV infection and part of the national combination prevention strategy. The analytical tools of value chains were used to elaborate the CAB LA value chain by identifying its links and activities. Three demand scenarios were defined based on target population data, varying geographic scope, and potential costs were calculated. CAB LA's value chain is divided into three major links: production, incorporation, and pharmaceutical assistance. Only the latter is considered for the calculation of costs under the budgetary responsibility of the MoH. Potential costs are estimated at R$15 million, R$19 million and R$21.8 million, in low, medium, and high demand scenarios, respectively. The study presents the potential costs for the MoH, including the need for tests and procedures, to guide public managers and the incorporation process. The lack of price for CAB LA is an important limitation of the results.