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1.
Immunity ; 55(6): 1013-1031.e7, 2022 06 14.
Article in English | MEDLINE | ID: mdl-35320704

ABSTRACT

Understanding the drivers and markers of clonally expanding HIV-1-infected CD4+ T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA+ T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB+ cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4+ T cells and drivers of clonal expansion provides another direction for HIV-1 eradication.


Subject(s)
HIV Infections , HIV-1 , CD4-Positive T-Lymphocytes , Clone Cells , Humans , RNA , Viremia
2.
J Infect Dis ; 229(4): 1141-1146, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38073467

ABSTRACT

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.


Subject(s)
HIV Infections , HIV-1 , Humans , Semen , Viral Load , Plasma , RNA, Viral
3.
N Engl J Med ; 384(11): 1003-1014, 2021 03 18.
Article in English | MEDLINE | ID: mdl-33730454

ABSTRACT

BACKGROUND: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. METHODS: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay. RESULTS: Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 µg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates. CONCLUSIONS: VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).


Subject(s)
Antibodies, Monoclonal/therapeutic use , Broadly Neutralizing Antibodies/therapeutic use , HIV Antibodies/therapeutic use , HIV Infections/prevention & control , HIV-1 , Adolescent , Adult , Africa South of the Sahara/epidemiology , Americas/epidemiology , Antibodies, Monoclonal/adverse effects , Broadly Neutralizing Antibodies/adverse effects , Double-Blind Method , Europe/epidemiology , Female , HIV Antibodies/adverse effects , HIV Infections/epidemiology , HIV-1/drug effects , Humans , Incidence , Male , Proof of Concept Study , Young Adult
4.
HIV Med ; 24(11): 1144-1149, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37386803

ABSTRACT

OBJECTIVES: Gender-affirming hormonal therapies (GAHT) and HIV increase cardiovascular risk for transgender women (TW), yet there is a paucity of data quantifying cardiometabolic changes following GAHT initiation, particularly among TW with HIV. METHODS: The Féminas study enrolled TW from October 2016 to March 2017 in Lima, Peru. Participants reported sexual activity that was high risk for HIV acquisition or transmission. All were tested for HIV/ sexually transmitted infection and were given access to GAHT (oestradiol valerate and spironolactone), HIV pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) for 12 months. Biomarker measurement was done on stored serum, whereas fasting glucose and lipids were measured in real time. RESULTS: In all, 170 TW (32 with HIV, 138 without HIV) had median age 27 years and 70% prior GAHT use. At baseline, PCSK9, sCD14, sCD163, IL-6, sTNFRI/II, CRP and EN-RAGE levels were significantly higher in TW with HIV than in TW without HIV. High-density lipoprotein and total cholesterol were lower and insulin and glucose parameters were similar. All TW with HIV started ART, but only five achieved virological suppression at any time. No TW without HIV initiated PrEP. Over 6 months, all participants initiated GAHT and had worsening insulin, glucose and HOMA-IR. Large d-dimer decreases also occurred. Similar changes occurred in TW with and without HIV. CONCLUSIONS: In this unique cohort of TW, GAHT decreased d-dimer but worsened insulin sensitivity. Because PrEP uptake and ART adherence were very low, observed effects are primarily attributed to GAHT use. Further study is needed to better understand cardiometabolic changes in TW by HIV serostatus.


Subject(s)
Cardiovascular Diseases , HIV Infections , Insulin Resistance , Insulins , Transgender Persons , Humans , Female , Adult , Proprotein Convertase 9 , HIV Infections/drug therapy , HIV Infections/prevention & control , Estradiol/therapeutic use , Glucose , Insulins/therapeutic use
6.
N Engl J Med ; 380(11): 1001-1011, 2019 03 14.
Article in English | MEDLINE | ID: mdl-30865794

ABSTRACT

BACKGROUND: Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates. METHODS: We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25. RESULTS: A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001). CONCLUSIONS: A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Antitubercular Agents/administration & dosage , HIV Infections/drug therapy , Isoniazid/administration & dosage , Latent Tuberculosis/drug therapy , Rifampin/analogs & derivatives , Tuberculosis/prevention & control , Adult , Antitubercular Agents/adverse effects , CD4 Lymphocyte Count , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/complications , Humans , Isoniazid/adverse effects , Latent Tuberculosis/complications , Male , Medication Adherence , Rifampin/administration & dosage , Rifampin/adverse effects
7.
AIDS Behav ; 26(3): 843-852, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34436712

ABSTRACT

To inform culturally relevant HIV prevention interventions, we explore the complexity of sex work among Peruvian transgender women. In 2015, we conducted twenty in-depth interviews and demographic surveys with transgender women in Lima, Peru to examine how transgender women enact individual- and community-level resistance strategies within a context of pervasive marginalization. Although 40% self-identified as "sex workers," 70% recently exchanged sex for money. Participants described nuanced risk-benefit analyses surrounding paid sexual encounters. Classification of clients as "risky" or "rewarding" incorporated issues of health, violence, and pleasure. Interviews highlighted context-informed decision-making (rejecting disrespectful clients, asserting condom use with specific partner types) demonstrating that motivations were not limited to HIV prevention or economic renumeration, but considered safety, health, attraction, gender validation, hygiene, and convenience. These findings underscore the complex risk assessments employed by Peruvian trans women. These individual-level decision-making and context-specific health promotion strategies represent critical frameworks for HIV prevention efforts.


Subject(s)
HIV Infections , Transgender Persons , Female , HIV Infections/prevention & control , Humans , Peru/epidemiology , Pleasure , Sex Work , Sexual Behavior
8.
AIDS Care ; 34(9): 1187-1195, 2022 09.
Article in English | MEDLINE | ID: mdl-34424782

ABSTRACT

HIV prevalence is high among transgender women, but little is known about cisgender men who have sex with transgender women (MSTW). The objective of this study was to investigate characteristics and behavior of MSTW compared to transgender women and men who have sex with men (MSM) using a modified respondent-driven sampling design. Seed participants completed a survey and invited up to three sex partners. Forward recruitment continued in waves through the referral of sex partners. Cross-sectional data were assessed using mixed effects models. From February to July 2018, 479 participants in Lima, Peru enrolled (n = 199 transgender women, n = 196 MSTW, and n = 45 MSM). MSTW behavior and identity differed significantly from that of transgender women and MSM. MSTW primarily identified as bisexual (69%) or heterosexual (15%) and only 6% reported male partners. Insertive condomless anal intercourse was reported by 61% of MSTW; 46% did not know their HIV serostatus. Compared to MSTW without male partners, those with recent male partners were more likely to sell sex (OR 15.7, 95% CI 4.1-60.5), and report condomless receptive anal intercourse (OR 89.0, 95% CI 19.1-414.8). This evidence suggests that MSTW are a distinct population from MSM, and highlights the critical need to include MSTW in HIV research and interventions.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Transgender Persons , Cross-Sectional Studies , Female , Gender Identity , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Peru/epidemiology , Risk-Taking , Sexual Behavior , Sexual Partners , Surveys and Questionnaires
9.
AIDS Care ; 34(5): 580-584, 2022 05.
Article in English | MEDLINE | ID: mdl-34011233

ABSTRACT

In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage within 90 days of HIV diagnosis by matching data from two studies conducted in Lima between 2013 and 2015 to national ART program records. We used generalized linear modeling to assess predictors of timely linkage and late presentation to care. Of 487 newly-diagnosed MSM and TW, only 44% presented for care at an HIV clinic within 90 days. Timely linkage was less common among TW (aPR 0.7, 95% CI 0.5-1.0), those younger than 24 (aPR 0.8, 95% CI 0.6-1.0), and those reporting a history of sex work (aPR 0.7, 95% CI 0.6-0.9). Proximity to an ART program clinic was not associated with linkage; most participants linked to clinics offering "LGBTQ-friendly" care. The pattern of clinics selected by participants suggests the importance of concerns about confidentiality and stigma in decision-making about where to link to care.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Transgender Persons , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Peru/epidemiology , Prevalence
10.
Arch Sex Behav ; 51(4): 1977-1991, 2022 05.
Article in English | MEDLINE | ID: mdl-35290540

ABSTRACT

Sexual and gender politics inform relational expectations surrounding sexual experiences of Peruvian transgender women (TW) and men who have sex with men (MSM). We used the framework of sexual role strain, or incongruence between preferred sexual role and actual sexual practices, to explore potential conflicts between personally articulated identities and externally defined norms of gender and sexuality and its potential to increase HIV/STI risk. Cross-sectional individual- and dyad-level data from 766 TW and MSM in Lima, Peru were used to assess the partnership contexts within which insertive anal intercourse was practiced despite receptive role preference (receptive role strain), and receptive anal intercourse practiced despite insertive role preference (insertive role strain). Sexual role strain for TW was more common with non-primary partners, while for MSM it occurred more frequently in the context of a primary partnership. Receptive role strain was more prevalent for TW with unknown HIV status (reference: without HIV) or pre-sex drug use (reference: no pre-sex drug use). For homosexual MSM, receptive role strain was more prevalent during condomless anal intercourse (reference: condom-protected) and with receptive or versatile partners (reference: insertive). Among heterosexual or bisexual MSM, insertive role strain was more prevalent with insertive or versatile partners (reference: receptive), and less prevalent with casual partners (reference: primary). Our findings suggest TW and MSM experience different vulnerabilities during sexual role negotiation with different partner-types. Future studies should explore the impact of sexual role strain on condom use agency, HIV/STI risk, and discordances between public and private presentations of gender and sexual orientation.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Sexually Transmitted Diseases , Transgender Persons , Cross-Sectional Studies , Female , HIV Infections/prevention & control , Homosexuality, Male , Humans , Male , Peru , Sexual Behavior , Sexual Partners
11.
Clin Infect Dis ; 72(6): 1042-1050, 2021 03 15.
Article in English | MEDLINE | ID: mdl-32107526

ABSTRACT

BACKGROUND: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits. METHODS: We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI). RESULTS: Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001). CONCLUSIONS: To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART. CLINICAL TRIALS REGISTRATION: NCT01815580.


Subject(s)
Anti-HIV Agents , HIV Infections , Sexual and Gender Minorities , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , Homosexuality, Male , Humans , Male , Peru/epidemiology
12.
Clin Infect Dis ; 73(3): e643-e651, 2021 08 02.
Article in English | MEDLINE | ID: mdl-33382405

ABSTRACT

BACKGROUND: Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation. METHODS: AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing. RESULTS: From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results. CONCLUSIONS: Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice. CLINICAL TRIALS REGISTRATION: NCT02859558.


Subject(s)
HIV Infections , HIV-1 , Adult , Africa , Asia , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Prospective Studies , Retrospective Studies
13.
AIDS Behav ; 25(6): 1873-1883, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33385279

ABSTRACT

We conducted a pilot randomized controlled trial of a social network-based intervention to promote PrEP adherence among transgender women (TW) in Lima, Peru. We enrolled 89 TW from six social networks and cluster-randomized them 1:1 to standard of care (n = 44) or the TransPrEP intervention (n = 45). Core workshops discussed strategies to support PrEP adherence and defined group adherence objectives. Maintenance workshops discussed participants' experiences taking PrEP and collective adherence goals. At 3-month follow-up, we evaluated 40 participants and obtained 29 hair samples for tenofovir level measurements. Though no significant differences were observed, 36.4% (4/11) of participants of TransPrEP participants and 10.0% (1/10) of control participants had tenofovir levels > 0.023 ng/mg, consistent with ≥ 4 doses per week. 81.8% (9/11) of intervention and 40.0% (4/10) of control participants had any detectable tenofovir in their hair. Pilot assessment of our network-based intervention suggested a trend towards improved PrEP adherence, measured objectively, for TW in Peru.


RESUMEN: Realizamos un estudio piloto controlado y aleatorizado de una intervención basada en redes sociales para promover la adherencia al PrEP en mujeres transgénero (MT) de Lima, Perú. Enrolamos a 89 MT de 6 redes sociales y las aleatorizamos por grupos a razón 1:1 al estándar de atención como control (n = 44) o a la intervención TransPrEP (n = 45). En los talleres centrales se discutieron estrategias para respaldar la adherencia al PrEP y se definieron los objetivos de adherencia del grupo. En los talleres de mantenimiento se discutieron las experiencias de los participantes al tomar PrEP y los objetivos de adherencia colectiva. A los 3 meses de seguimiento, evaluamos a 40 participantes y obtuvimos 29 muestras de cabello para medir el nivel de tenofovir. Aunque no se observaron diferencias significativas, el 36.4% (4/11) de los participantes de TransPrEP y el 10.0% (1/10) de los participantes del grupo control tenían niveles de tenofovir> 0.023 ng/mg, congruente con 4 o más dosis por semana. El 81.8% (9/11) del grupo de intervención y el 40.0% (4/10) de los participantes de control tenían tenofovir detectable en el cabello. La evaluación piloto de nuestra intervención basada en redes sugiere una tendencia hacia una mejor adherencia al PrEP, medida objetivamente, para las MT en Perú.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Transgender Persons , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Homosexuality, Male , Humans , Male , Medication Adherence , Peru , Pilot Projects , Social Networking
14.
Arch Sex Behav ; 50(7): 3287-3295, 2021 10.
Article in English | MEDLINE | ID: mdl-34617189

ABSTRACT

While transgender women have been identified as a global priority population for HIV prevention and treatment, little is known about the cisgender male partners of transgender women, including their sexual behavior and HIV prevalence. Previous research has suggested that these male partners have varied identities and sexual behavior, which make identifying and engaging them in research difficult. This paper describes interviews conducted with fifteen cisgender men who reported recent sexual activity with transgender women in Lima, Peru. The purpose of this research was to explore how these men reported their identities and sexual behavior, to better understand how they would interact with HIV outreach, research, and care. The major themes were sexual orientation and identity; view of transgender partners; social ties to transgender women and other men with transgender women partners; disclosure of relationships; HIV knowledge and risk perception; and attitudes toward interventions. We found that language used to assess sexual orientation was problematic in this population, due to lack of consistency between orientation and reported behavior, and unfamiliarity with terms used to describe sexual orientation. In addition, stigma, lack of knowledge of HIV prevention methods, and fear of disclosure of sexual behavior were identified as barriers that could impact engagement in HIV research, prevention, and care. However, participants reported social relationships with both transgender women and other men who have transgender partners, presenting possible avenues for recruitment into HIV research and healthcare services.


Subject(s)
HIV Infections , Transgender Persons , Transsexualism , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , Homosexuality, Male , Humans , Male , Sexual Behavior
15.
Clin Infect Dis ; 71(10): 2645-2654, 2020 12 17.
Article in English | MEDLINE | ID: mdl-31761933

ABSTRACT

BACKGROUND: People with advanced human immunodeficiency virus (HIV) (CD4 < 50) remain at high risk of tuberculosis (TB) or death despite the initiation of antiretroviral therapy (ART). We aimed to identify immunological profiles that were most predictive of incident TB disease and death. METHODS: The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4 < 50 cells/µL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n = 257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. RESULTS: In total, 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (interleukin [IL]-1ß, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1ß, IL-10, sCD14, tumor necrosis factor [TNF]-α, and TNF-ß) achieved a sensitivity of 0.90 (95% confidence interval [CI]: .87-.94) and a specificity of 0.71(95% CI: .68-.75) with an area under the curve (AUC) of 0.81 (95% CI: .78-.83) for incident TB. CONCLUSION: Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions. CLINICAL TRIALS REGISTRATION: NCT01380080.


Subject(s)
HIV Infections , Tuberculosis , Antitubercular Agents/therapeutic use , Biomarkers , CD4 Lymphocyte Count , Cohort Studies , HIV , HIV Infections/complications , HIV Infections/drug therapy , Humans , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology
16.
Sex Transm Dis ; 47(12): 825-831, 2020 12.
Article in English | MEDLINE | ID: mdl-33186338

ABSTRACT

BACKGROUND: We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017). METHODS: Sabes participants were tested monthly for HIV to identify acute or early infections, and HIV-positive participants were randomized to receive antiretroviral therapy immediately (immediate arm) or after 24 weeks (deferred arm) during a 48-week follow-up period. Sexual behavior was assessed at randomization (baseline) and every 12 weeks thereafter. Participants were tested for urethral and rectal chlamydia and gonorrhea and for syphilis at baseline, 12, 24, and 48 weeks. We describe patterns of sexual behavior during the 48-week follow-up period and compare sexual behavior and STI incidence between study arms. RESULTS: After randomization, 207 HIV-positive participants completed questionnaires and STI testing at 2 or more visits. After HIV diagnosis, participants in both arms reported increases in condom use with main and casual partners and decreased drug and alcohol use before or during anal sex. We observed no between-arm differences in sexual behavior. Deferred arm participants had higher incidence of chlamydia (incidence rate ratio, 2.33; 95% confidence interval, 1.14-4.77) but not gonorrhea or syphilis. CONCLUSIONS: Despite reported increases in condom use, the overall high incidence of STIs reflects some ongoing condomless sex among HIV-positive men who have sex with men and transgender women, highlighting the importance of regular STI screening and counseling to support consistent condom use among HIV-positive individuals at risk for STIs.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Homosexuality, Male/psychology , Sexual Behavior/statistics & numerical data , Transgender Persons/psychology , Adult , Female , HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Humans , Male , Peru/epidemiology , Sexual Partners , Sexual and Gender Minorities , Sexually Transmitted Diseases/epidemiology , Transgender Persons/statistics & numerical data
17.
AIDS Behav ; 24(3): 914-924, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31300977

ABSTRACT

HIV prevalence is high among transgender women (TW), but how HIV is transmitted to this population is not well understood. This analysis aims to characterize sexual partners of TW (PTW) to understand how their behavior contributes to HIV risk among TW. We examined baseline data from TW, PTW, and men who have sex with men (MSM) from a treatment-as-prevention study in Lima, Peru. Individual and partnership characteristics were compared across groups, and Poisson regression was used to calculate prevalence ratios for associations between sexual concurrency and potential correlates. We found that 81% of PTW had no cisgender male partners. Prevalence of alcohol dependency, concurrency, and condomless anal intercourse was high and HIV testing was low compared to the other groups. Our results suggest that PTW are a distinct population from MSM and TW, engage in behavior associated with HIV transmission, and are likely not well reached by HIV prevention interventions.


Subject(s)
Alcoholism/epidemiology , HIV Infections/epidemiology , Sexual Behavior/statistics & numerical data , Sexual Partners , Transgender Persons , Adult , Bisexuality , Female , HIV Infections/prevention & control , Heterosexuality , Homosexuality, Male , Humans , Male , Peru/epidemiology , Prevalence , Sexual and Gender Minorities , Unsafe Sex/statistics & numerical data , Young Adult
18.
AIDS Behav ; 24(6): 1743-1751, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31720954

ABSTRACT

Limited data exists on intimate partner violence (IPV) among transgender women (TW), though global trends suggest IPV is associated with HIV risk in this population. We describe the prevalence of verbal, physical, and/or sexual violence as well as participant- and partner-level correlates of IPV among TW in Lima, Peru. Among 389 respondents, 15.2% reported IPV with one or more of their last three sexual partners: 9.2% verbal, 8.2% physical, and 2.3% sexual violence. Physical and verbal violence were more common with stable partners (aPR 3.46, 95% CI 1.17-10.25, aPR 2.46, 95% CI 1.14-5.28, respectively). Physical violence was associated with condomless receptive anal intercourse (cRAI) (aPR 2.22, 95% CI 1.19-4.13) and partner alcohol use (aPR 4.38, 95% CI 1.56-12.33) while verbal violence correlated with participant inebriation (aPR 4.86, 95% CI 1.63-14.46). Our results link IPV with stable partnerships, alcohol use, and cRAI, suggesting TW in Peru may benefit from multidimensional IPV prevention strategies to foster supportive relationships and reduce HIV transmission.


Subject(s)
Alcohol Drinking/adverse effects , Condoms/statistics & numerical data , Intimate Partner Violence/statistics & numerical data , Sex Offenses , Sexual Partners , Transgender Persons/statistics & numerical data , Unsafe Sex/statistics & numerical data , Adolescent , Adult , Alcohol Drinking/psychology , Female , Humans , Intimate Partner Violence/psychology , Male , Middle Aged , Peru/epidemiology , Prevalence , Sex Offenses/psychology , Sex Offenses/statistics & numerical data , Sexual Behavior , Transgender Persons/psychology , Young Adult
19.
Subst Use Misuse ; 55(3): 399-404, 2020.
Article in English | MEDLINE | ID: mdl-31682179

ABSTRACT

Background: Binge drinking (BD) is common in Peru, but may not be routinely detected by standard assessments of hazardous drinking. Objectives: We describe prevalence and risk behaviors of men who have sex with men (MSM) and transgender women (TW) in Peru who met criteria for BD as compared with those who met criteria for hazardous drinking. Methods: In a cross-sectional sample of MSM and TW from Lima (2012-2014), we calculated prevalence of BD (consuming ≥6 alcoholic drinks per occasion by AUDIT-3 criteria), conducted bivariate analyses of associations of BD with demographic and behavioral characteristics, and compared prevalence and behaviors of BD to those of hazardous drinkers (identified by AUDIT-10 criteria). Results: Of 1,520 MSM (n = 1,384) and TW (n = 137) with median age 27 years, 74.4% of MSM and 86.9% of TW met criteria for BD. Among MSM, BD was associated with a greater likelihood of using alcohol (41.6% vs. 13.8%; p < .01) or drugs (7.8% vs. 2.8%; p < .01) prior to a recent sexual contact. Among TW, BD was associated with greater frequency of alcohol use (44.9% vs. 11.1%; p < .01) or unprotected anal intercourse (58.8% vs. 33.3%; p = .04) during ≥1 of their three most recent sexual contacts. There was a higher prevalence of BD (75.5%) than hazardous drinking (53.2%) in our sample, with binge drinkers exhibiting similar sexual risk behaviors to hazardous drinkers. Conclusions: Binge drinking is common among MSM and TW in Lima, associated with risky sexual behavior, and may not be adequately captured by AUDIT-10 criteria.


Subject(s)
Binge Drinking , Risk-Taking , Sexual and Gender Minorities , Transgender Persons , Adult , Binge Drinking/epidemiology , Cross-Sectional Studies , Female , Homosexuality, Male , Humans , Male , Peru/epidemiology , Unsafe Sex , Young Adult
20.
Sex Transm Infect ; 95(5): 336-341, 2019 08.
Article in English | MEDLINE | ID: mdl-31010954

ABSTRACT

OBJECTIVE: While men who have sex with men (MSM) are disproportionately affected by Peru's overlapping HIV and STI epidemics, there are few data on how partnership-level and network-level factors affect STI transmission in Peru. We explored partnership-level and network-level factors associated with gonorrhoea/chlamydia (Neisseria gonorrhoeae and/or Chlamydia trachomatis (NG/CT)) and/or syphilis infection among MSM in Peru. METHODS: We present the results of a cross-sectional secondary analysis of MSM (n=898) tested for syphilis and NG/CT infection as part of the screening process for two STI control trials in Lima, Peru. Participants completed questionnaires on demographics, sexual identity and role, characteristics of their three most recent sexual partners (partner sexual orientation, gender, role, partnership type, partner-specific sexual acts) and 30-day sexual network characteristics (number of sexual partners, partnership types, frequency of anal/vaginal intercourse). Participants were tested for syphilis and urethral, rectal and oropharyngeal NG/CT. Differences in network characteristics were analysed with χ2 and Kruskal-Wallis tests. RESULTS: Approximately 38.9% of participants had a new STI diagnosis (syphilis (rapid plasma reagin ≥16): 10.6%; NG/CT: 22.9%; syphilis-NG/CT coinfection: 5.4%). Condomless anal intercourse (CAI) was not significantly associated with an STI diagnosis. Gay-identified participants with exclusively homosexual networks had a higher prevalence of STIs (47.4%) than gay-identified MSM with only heterosexual/bisexual partners (34.6%, p=0.04), despite reporting fewer sexual partners (any partners: 2, 1-4 vs 3, 2-6; p=0.001; casual partners: 1, 0-3 vs 2, 1-4; p=0.001) and more stable partnerships (1, 0-1 vs 0, 0-1; p=0.003) in the last month. CONCLUSIONS: Network size and the number of casual sexual partners were associated with NG/CT infection among MSM in Peru. Despite reporting fewer sexual risk behaviours (smaller network size, more stable partnerships, less CAI), MSM with homosexual-only sexual networks had a higher prevalence of NG/CT and syphilis. These findings suggest network composition among MSM in Peru plays an important role in the risk for STI acquisition.


Subject(s)
Chlamydia Infections/epidemiology , Gonorrhea/epidemiology , Sexual and Gender Minorities/statistics & numerical data , Syphilis/epidemiology , Adult , Chlamydia Infections/diagnosis , Chlamydia Infections/prevention & control , Chlamydia Infections/psychology , Cross-Sectional Studies , Female , Gonorrhea/diagnosis , Gonorrhea/prevention & control , Gonorrhea/psychology , Homosexuality, Male , Humans , Male , Middle Aged , Peru/epidemiology , Sex Workers/statistics & numerical data , Sexual Behavior , Sexual Partners , Syphilis/diagnosis , Syphilis/prevention & control , Syphilis/psychology , Young Adult
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