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1.
J Antimicrob Chemother ; 77(2): 500-506, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-34791296

RESUMEN

BACKGROUND: Tenofovir disoproxil fumarate-containing pre-exposure prophylaxis (PrEP) has been associated with decreases in bone mineral density (BMD), but the bone effects of other non-tenofovir disoproxil fumarate candidate PrEP regimens are not well described. METHODS: The HPTN 069/ACTG A5305 study randomized 406 US cisgender men and transgender women, and 188 cisgender women at risk for HIV infection to one of four double-blinded regimens: (i) maraviroc; (ii) maraviroc + emtricitabine; (iii) maraviroc + tenofovir disoproxil fumarate; or (iv) tenofovir disoproxil fumarate + emtricitabine. BMD was measured in a subset of participants at the lumbar spine (LS) and hip by dual-energy X-ray absorptiometry (DXA) at baseline and 48 weeks. Percentage change in LS and hip BMD was compared between the tenofovir disoproxil fumarate- and non-tenofovir disoproxil fumarate-containing arms by Wilcoxon rank-sum tests and multiple linear regression adjusting for sex, race and baseline BMI. RESULTS: At baseline (n = 307), the median age was 33 years, 56% male and 43% black. At the hip, the median percentage change in BMD at 48 weeks was -1.05% in the tenofovir disoproxil fumarate arms and 0.0% in the non-tenofovir disoproxil fumarate arms (between group P = 0.001). No interaction by sex was observed. The median percentage change in LS BMD was not different between arms. CONCLUSIONS: Tenofovir disoproxil fumarate-containing PrEP was associated with significantly greater bone loss compared with maraviroc ± emtricitabine PrEP at the hip, but not the LS. The BMD changes at the hip were similar in magnitude in men and women.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Método Doble Ciego , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Masculino , Maraviroc/uso terapéutico , Tenofovir/uso terapéutico
2.
J Infect Dis ; 217(11): 1770-1781, 2018 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-29401318

RESUMEN

Background: Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. Methods: In this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Results: Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was -2.6 percentage points (P = 0.08) in lymph node specimens and -1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by -0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (-1.0 percentage point; P = .001) and fibronectin deposition (-2.4 percentage points; P < .001) were observed, with no between-arm differences. Conclusions: In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Antihipertensivos/uso terapéutico , Fibrosis/tratamiento farmacológico , Ganglios Linfáticos/efectos de los fármacos , Telmisartán/uso terapéutico , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Tejido Adiposo/virología , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Femenino , Fibrosis/metabolismo , Fibrosis/patología , Fibrosis/virología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Inflamación/virología , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Masculino , Persona de Mediana Edad , PPAR gamma/metabolismo
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