University of Louisville Hospital, Louisville, Kentucky

9-323

Current antiretroviral therapy prescribing practices in HIV-infected men versus women with drug resistance mutations

Lauren Kirkpatrick, PharmD; Mary Bishop, RPh, AAHIVP; Cathy Spencer, PharmD, BCPS, AAHIVP; Jennifer Wiedmar, PharmD, BCCCP, BCPS; Daniel Truelove, PharmD, BCPS (AQ-ID), BCACP, AAHIVP

University of Louisville Hospital, Louisville, Kentucky

Background

Current HIV treatment guidelines are based on evidence from clinical trials enrolling 80% men.1 Existing literature suggests that sex-based differences in antiretroviral efficacy and pharmacokinetics may exist, but previous trials lack appropriate power to demonstrate a statistically significant difference due to small sample sizes of women and high drop-out rates.1-4 Authors of these studies conclude further trials with an adequate representation of women would provide more information on efficacy and potential pharmacokinetic differences of antiretroviral agents.3,4

Literature Evaluating Gender Differences

Currier, et al.3

Women had higher drug exposure to certain antiretroviral agents such darunavir and ritonavir.

Sax, et al.4

Women had a significantly better efficacy with tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF). This difference was not observed in men.

In addition to under-representation of women in clinical trials, there is minimal data evaluating sex-based differences for patients with drug resistance mutations to antiretroviral agents used in HIV treatment. Current HIV treatment guidelines recommend using a regimen that contains three fully active antiretroviral agents in patients with drug resistance mutations.5

From August 2014 to June 2015, a pilot study was conducted at the University of Louisville HIV Clinic, specifically focusing on prescribing practices in HIV-infected females with resistance mutations.6

? M184V was the most common mutation

(M184V: High level of resistance to emtricitabine, but enhanced susceptibility to TDF7)

? Most commonly prescribed regimen for patients with M184V was emtricitabine/TDF and a boosted protease inhibitor (PI), which only contains two fully active agents in the presence of this mutation

? Viral suppression was attained more commonly with this regimen when compared to regimens containing three fully active antiretroviral agents

Results suggest that regimens containing two active drugs may be as efficacious as a three drug regimen in women with the M184V mutation. This could reduce daily pill burden for patients and reduce medication costs, potentially increasing adherence.6 Outcomes from this study raise questions about if this effect is also observed in men with drug resistance mutations on similarly prescribed antiretroviral regimens.

Purpose

To determine if gender differences impact the ability to attain viral suppression in patients with drug resistance mutations.

Methods

? Single center, retrospective electronic medical record review conducted October 1, 2016 through January 1, 2017 ? University of Louisville Institutional Review Board approved October 2016 ? Patients receiving HIV treatment at the University of Louisville HIV Clinic from January 1, 2003 to July 30, 2016

Inclusion Criteria > 1 major drug resistance mutation

Exclusion Criteria

? Lack of a genotype result prior to initiating or changing antiretroviral therapy

? Inadequate documentation of viral load or CD4 counts prior to and/or following the initiation of new therapy

Matching Criteria

? Age ? Length of HIV diagnosis ? Viral load and CD4 count at time

of genotyping

? This study focused on prescribing practices in HIV-infected men compared to women with one or more drug resistance mutation(s) ? The most common drug resistance mutations were identified and drug regimens were evaluated for viral suppression success ? Data was analyzed using descriptive statistics, Chi-square tests, and logistic regression

Outcomes

Primary Outcome

Proportion of men achieving viral suppression (HIV-1 RNA < 200 copies/mL) compared to women

Secondary Outcomes

Proportion of patients achieving viral suppression on regimens with two fully active antiretroviral agents compared to three fully active agents

549 male cases identified 01/1/2003 - 07/30/2016

Preliminary Data

Most Common Mutations in Men

30

Excluded n=154

Included n=43

25

25

Number of Reported Mutations

No major drug resistance mutation

n=145

No documented genotype

n=9

Baseline Characteristics

Age (yr)

45.7 + 10.5

Ethnicity (n,%) African American Caucasian Other

21 (48.8) 17 (39.5) 5 (11.6)

Diagnosis Date 1999-2004 2005-2009 2010-2014

9 (20.9) 21 (48.8) 13 (30.2)

Treatment Na?ve

13 (30.2)

Treatment Experienced >3 antiretrovirals 3 antiretrovirals

9 (20.9) 21 (48.8)

20

15

12

10

6

6

5

4

0

M184V/I

K103N M41L

K65R

Resistance Mutations

L100I

Preliminary Results

Viral Suppression in Men with M184V/I Mutation

VL and CD4 count at genotyping

Two fully active ARV Three fully active ARV

(n=12)

(n=13)

VL > 100,000 & CD4 < 200

0/3

2/4

VL < 100,000 & CD4 > 200

6/7

5/7

VL < 100,000 & CD4 < 200

Total percent achieving viral suppression

1/2 58.3%

1/2 61.5%

Future Considerations

The preliminary data was collected from October 1, 2016 through November 18, 2016. Data will continue to be collected through the predetermined endpoint of January 1, 2017. After all data is collected, male patients will be matched with female patients based on the previously specified criteria and outcomes will be analyzed to determine if gender differences impact the ability to attain viral suppression in patients with drug resistance mutations.

Study Limitations

The study design is limited in that it is a single center study, which can lend to its internal validity, but the utility of this study to other institutions may not be as strong. In addition, with a retrospective study design we are unable to measure medication adherence to antiretroviral regimens. Lack of adherence has a huge impact on the development of drug resistance mutations and ability to achieve viral suppression. To minimize this limitation, it was only reported whether viral suppression was ever achieved or not on the newly prescribed antiretroviral regimen rather than how long the patient maintained viral suppression.

References

1. Firnhaber C, Smeaton LM, Grinsztejn B, et al. Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial. HIV Clin Trials. 2015 May-Jun;16(3):89-99.

2. Soon G, Min M, Struble K, et al. Meta-Analysis of Gender Differences in Efficacy Outcomes for HIV-Positive Subjects in Randomized Controlled Clinical Trials of Antiretroviral Therapy (2000?2008). AIDS Patient Care STDS. 2012 Aug;26(8):444-53.

3. Currier J, Bridge D, Haggins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: The GRACE (Gender, Race, and Clinical Experience) Study. Ann Intern Med. 2010; 153(6): 349-357.

4. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomized, double-blind, phase 3, non-inferiority trials. Lancet. 2015 Jun 27;385(9987):2606-15.

5. DHHS Panel. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. .

6. Wojak M, Peyrani P, Bishop M, Cox M, Truelove D. Current practices in prescribing antiretroviral therapy in HIV-infected female patients with resistance mutations: experience from an academic-based HIV clinic. ASHP Midyear Clinical Meeting Poster Presentation 2014.

7. Soo-Yon Rhee, Matthew J. Gonzales, Rami Kantor, Bradley J. Betts, Jaideep Ravela, and Robert W. Shafer (2003) Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Research, 31(1), 298-303.

Disclosure

Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have direct or indirect interest in the subject matter of this presentation.

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