P20 Triple protease inhibitor combinations in patients with multidrug resistant HIV infection

Abstract Background Individuals with HIV infection is at increased risk of low area bone mineral density (BMD) and fracture. However, data regarding volumetric BMD (vBMD) of central bone determined by quantitative computed tomography (QCT) which can distinguish the cortical and trabecular bone component are limited. Methods From November 2017 to October 2018, we measured spine and hip vBMD in HIV-infected men aged 30 years or older at the tertiary center. QCT data were compared with 1:2 matched control by age- and body mass index (BMI) sampled from a community-based healthy individual cohort. HIV-specific risk factors for low total hip vBMD as a primary outcome were identified using multivariate linear regression models. Results A total of 83 HIV-infected men and 166 control were analyzed (mean age 47.4 vs. 47.0 year; BMI 23.3 vs. 23.7 kg/m2; P > 0.05). In HIV-infected men, vBMD of trochanter, intertrochanter and total hip was significantly lower than that of non-infected men. (198 ± 31 vs. 213 ± 32; 339 ± 50 vs. 356 ± 47; 280 ± 41 vs. 296 ± 41 mg/cc; all P < 0.05) Association between HIV infection and lower total hip vBMD remained robust (Adjusted β -14.4; P = 0.013) after adjustment for age, diabetes, smoking, and vitamin D status. In HIV cohort, low CD4 T-cell count at initial diagnosis (< 200 vs. ≥200 cells/μL; Adjusted β = −6.7, P = 0.015) and use of protease inhibitor (vs. integrase inhibitor; Adjusted β = −29.9, P = 0.029) were negatively associated with total hip vBMD, after adjustment for age, BMI, and duration of HIV infection, whereas tenofovir disoproxil fumarate use was not. (Adjusted β −12.1, P = 0.280) In HIV-infected men with low tertile total hip vBMD, the levels of β-crosslaps (0.42 ± 0.23 vs. 0.30 ± 0.16 ng/mL; P = 0.012) and osteocalcin (22.10 ± 8.65 vs. 16.57 ± 6.04 ng/mL; P = 0.001) were higher than those with middle-upper tertile total hip vBMD. Conclusion HIV-infected men had lower hip vBMD compared with age- and BMI-matched non-infected men. Low baseline CD4 T-cell count and protease inhibitor use were independent risk factors for lower total hip vBMD. High born turnover was attributable to the negative effect on born health of HIV-infected men. Disclosures All authors: No reported disclosures.

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Protease inhibitor therapy for HIV infection: the effect on HIV-associated nephrotic syndrome

Nephrology Dialysis Transplantation ◽

10.1093/ndt/14.3.744 ◽

1999 ◽

Vol 14 (3) ◽

pp. 744-747 ◽

Cited By ~ 20

Author(s):

E. Dellow ◽

R. Unwin ◽

R. Miller ◽

I. Williams ◽

M. Griffiths

Keyword(s):

Nephrotic Syndrome ◽

Hiv Infection ◽

Protease Inhibitor ◽

Inhibitor Therapy ◽

Protease Inhibitor Therapy

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Cervicovaginal Levels of Lactoferrin, Secretory Leukocyte Protease Inhibitor, and RANTES and the Effects of Coexisting Vaginoses in Human Immunodeficiency Virus (HIV)-Seronegative Women with a High Risk of Heterosexual Acquisition of HIV Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00386-06 ◽

2007 ◽

Vol 14 (9) ◽

pp. 1102-1107 ◽

Cited By ~ 62

Author(s):

Richard M. Novak ◽

Betty A. Donoval ◽

Parrie J. Graham ◽

Lucy A. Boksa ◽

Gregory Spear ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

High Risk ◽

Hiv Infection ◽

Protease Inhibitor ◽

Genital Tract ◽

Secretory Leukocyte Protease Inhibitor ◽

Low Risk ◽

High Risk Women ◽

Increased Risk ◽

Immunodeficiency Virus

ABSTRACT Innate immune factors in mucosal secretions may influence human immunodeficiency virus type 1 (HIV-1) transmission. This study examined the levels of three such factors, genital tract lactoferrin [Lf], secretory leukocyte protease inhibitor [SLPI], and RANTES, in women at risk for acquiring HIV infection, as well as cofactors that may be associated with their presence. Women at high risk for HIV infection meeting established criteria (n = 62) and low-risk controls (n = 33) underwent cervicovaginal lavage (CVL), and the CVL fluid samples were assayed for Lf and SLPI. Subsets of 26 and 10 samples, respectively, were assayed for RANTES. Coexisting sexually transmitted infections and vaginoses were also assessed, and detailed behavioral information was collected. Lf levels were higher in high-risk (mean, 204 ng/ml) versus low-risk (mean, 160 ng/ml, P = 0.007) women, but SLPI levels did not differ, and RANTES levels were higher in only the highest-risk subset. Lf was positively associated only with the presence of leukocytes in the CVL fluid (P < 0.0001). SLPI levels were lower in women with bacterial vaginosis [BV] than in those without BV (P = 0.04). Treatment of BV reduced RANTES levels (P = 0.05). The influence, if any, of these three cofactors on HIV transmission in women cannot be determined from this study. The higher Lf concentrations observed in high-risk women were strongly associated with the presence of leukocytes, suggesting a leukocyte source and consistent with greater genital tract inflammation in the high-risk group. Reduced SLPI levels during BV infection are consistent with an increased risk of HIV infection, which has been associated with BV. However, the increased RANTES levels in a higher-risk subset of high-risk women were reduced after BV treatment.

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Darunavir (Prezista): A HIV-1 Protease Inhibitor for Treatment of Multidrug-Resistant HIV

Modern Drug Synthesis ◽

10.1002/9780470768594.ch3 ◽

2010 ◽

pp. 29-44 ◽

Cited By ~ 3

Author(s):

Arun K. Ghosh ◽

Cuthbert D. Martyr

Keyword(s):

Protease Inhibitor ◽

Multidrug Resistant ◽

Hiv 1

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Managing the Patient with Multidrug-Resistant HIV

10.1093/med/9780190493097.003.0022 ◽

2017 ◽

Author(s):

Ye Thu ◽

Naiel Nassar

Keyword(s):

Hiv Infection ◽

Treatment Guidelines ◽

Virologic Failure ◽

Multidrug Resistant ◽

Fixed Dose ◽

Combination Product ◽

The Past ◽

Antiretroviral Medication ◽

Dose Combination ◽

Therapy Treatment

During approximately the past 15 years, HIV infection has been transformed into a chronic manageable disease primarily due to the effectiveness of antiretroviral therapy. Treatment guidelines emphasize the need for at least two or preferably three fully active medications in the salvage regimens of patients experiencing virologic failure. The new regimen should be started with as little interruption as possible because the structured interruption of treatment in patient with multidrug-resistant HIV infection is associated with greater progression of the disease. The new pharmacokinetic enhancer, cobicistat, is available as a fixed-dose combination product with antiretroviral medication that allows the treatment to be simplified and reduces the pill burden.

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