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  5th IAS Conference on HIV Pathogenesis, Treatment and Prevention
July 19th-22nd 2009
Capetown, South Africa
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African-American Women Need Services is Highlighted in: GRACE (Gender, Race And Clinical Experience): 48-Week Results of Darunavir/r-based Therapy in the Largest Trial in North America to Focus on Treatment-experienced Women
  "Discontinuations due to loss to follow up, relocation and withdrawal of consent reflect challenges that may be unique to women with respect to clinical trials"
Reported by Jules Levin, 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, South Africa, July 19-22, 2009
FROM JULES: As I have been saying the 2 biggest problems in HIV in the USA are related to African-Americans and aging (senesence, immune activation etc) but no one really listens or responds to these issues. This data from GRACE & the data reported by Kim Smith from HEAT show African-American women had lower viral responses and in GRACE this was found to be due to discontinuations lost to follow-up, relocation, withdrawal of consent....African-Americans, particularly African-American women, and Latinos as well, need better support services. This is more obvious now to ALL. The Federal & State governments and the drug companies should be more responsive to these needs, but I doubt the Federal government will. Their decisions are made on politics not need for patients. In addition the HEAT Study reported in a poster today that African-American women also had a worse virologic response. GRACE reported that African-American women discontinue therapy or drop out of the study; and this is likely due to a need for better support services. 
Kathleen Squires1; Judith Currier2; Dawn Averitt Bridge3; Debbie Hagins4; Carmen Zorrilla5; Robert Ryan6; Ron Falcon7;
Alan Tennenberg7; Joseph Mrus7; on behalf of the GRACE Study Group 1Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA; 2University of California, Los Angeles, School of Medicine, Los Angeles, CA, USA;
3The Well Project, Inc., Atlanta, GA, USA; 4Chatham County Health Department, Savannah, GA, USA; 5University of Puerto Rico School of Medicine, San Juan, PR, USA;
6Tibotec, Inc., Yardley, PA, USA; 7Tibotec Therapeutics, Bridgewater, NJ, USA
In the ITT-TLOVR analysis, which treats all study discontinuations as failures, the difference in virologic response rates between men and women was 9.6% (CI:
-19.9%, 0.7%) at Week 48
- After accounting for differential rates of discontinuation for men and women due to reasons other than VF, the response rates for men and women were similar
Women had significantly higher increases in CD4+ count compared with men in the observed analyses, as noted in previous ARV trials
Treatment with DRV/r was similarly tolerated between women and men, with no unexpected AEs, based on results from previous trials5-8
- No specific AE was identified as driving discontinuations in either group
Discontinuations due to loss to follow up, relocation and withdrawal of consent reflect challenges that may be unique to women with respect to clinical trials

The GRACE study successfully enrolled a high proportion of women and is, to date, the largest study in North America to assess sex-based differences in the efficacy and safety of an ARV regimen
Overall, the data from GRACE suggest that DRV/r can be used in women and men with similar safety and efficacy outcomes
Higher rates of discontinuation among women highlight the need for investigation into the retention of women in clinical trials
- Addressing the unique needs and challenges of women during the screening process and throughout the study may improve study retention
GRACE provides insight for the development and design of future clinical trials
- Setting a requirement of enrolling three women to one man appears to be an effective method of increasing the enrollment of women
Women account for an increasing proportion of patients living with HIV/AIDS in the United States (US)1,2, yet data on the effi cacy and safety of antiretrovirals (ARVs) in women are limited
- Several challenges, including socioeconomic factors, have led to difficulties in recruiting and retaining women in ARV clinical trials
Darunavir (DRV; PREZISTA), a protease inhibitor (PI) combined with a low dose of ritonavir (DRV/r), has been approved for use in the US as a therapeutic option for treatment-experienced, treatment-naïve and pediatric (aged 6 to <18 years) HIV-infected patients3 · We report 48-week results from the primary analysis of the GRACE (Gender, Race And Clinical Experience) trial, which was designed to enroll a high proportion of treatment-experienced women, in order to assess sex-based differences in the efficacy and safety of DRV/r-based therapy
- Analyses by race will be presented elsewhere
Study design and treatment

Open-label, single-arm, Phase IIIb study conducted at 65 sites across the US, Puerto Rico and Canada for 48 weeks (Figure 1)
Samples taken at screening and at virologic failure (VF) were analyzed for resistance by Virco®TYPE HIV-1 genotype and predicted phenotype analysis (Virco BVBA, Mechelen, Belgium)


aPatients were allowed to enter the study on treatment interruption of ≥4 weeks; bInvestigator-selected NRTIs and NNRTIs were allowed; ENF, TPV or agents from novel classes were not allowed; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; HAART, highly-active antiretroviral therapy; DRV/r, darunavir/ritonavir; ETR, etravirine; ENF, enfuvirtide; TPV, tipranavir; bid, twice daily; OBR, optimized background regimen





a'Other' classification was selected by the investigator as reason for discontinuation; 'Other' reasons for discontinuation that each occurred in one woman only were sponsor's decision, safety (older patient taking too many concomitant medications), no decrease in viral load, time restraints on visit attendance and new antiretroviral regimen started in favor of study medication; 'Other' reasons for discontinuation that each occurred in one man only were ineligibility to continue treatment and site closure


aSignificantly different for women and men (P<.05); bBy Virco®TYPE; SD, standard deviation; BMI, body mass index; CDC, Centers for Disease Control and Prevention; PI, protease inhibitor; IAS, International AIDS Society



aThe 95% confi dence interval (CI) crossed zero for both ITT and non-VF censored analyses; The 95% CI only included
-15% in the ITT-TLOVR analysis; ITT, intent-to-treat; TLOVR, time-to-loss of virologic response; VF, virologic failure
The median change from baseline in the observed CD4+ count was higher in women than men (Figure 4)
The median change from baseline in CD4+ count for the ITT-last observation carried forward analysis was similar in women and men (Figure 4)


aThe least-squares mean difference between sexes in the observed and ITT-LOCF analyses, adjusted for baseline viral load and CD4+ count, was 34\ cells/mm3 (95% confi dence interval [CI]: 0.4, 68; P=.047) and 11 cells/mm3 (95% CI: -18, 39; P=>.05), respectively; ITT, intent-to-treat; LOCF, last observation carried forward


aOut of 82 women and 42 men with confi rmed virologic failure (HIV-1 RNA >50 copies/mL), 27 and 17, respectively, had genotypes available at baseline and virologic failure; bGenotype determined only for patients with HIV-1 RNA >1000 copies/mL; IAS, International AIDS Society; PI, protease inhibitor; RAM, resistance-associated mutation; NRTI, nucleoside reverse transcriptase inhibitor; DRV, darunavir
Overall, 259 (90.2%) women and 118 (83.1%) men experienced at least one AE (Table 3)
- The majority of AEs were mild-to-moderate in severity
- In total, 134 (46.7%) women and 61 (43.0%) men experienced at least one AE considered by the investigator to be at least possibly related to DRV/r
The most common AEs were nausea (women, 24.4%; men, 14.1%), diarrhea (women, 16.4%; men, 22.5%), upper respiratory tract infection (women, 11.1%; men, 7.7%) and vomiting (women, 11.5%; men, 6.3%)
Serious AEs were reported in 47 (16.4%) women and 33 (23.2%) men; the mostcommonly reported were pneumonia (2.6% overall) and Pneumocystis jiroveci pneumonia (1.2% overall)
- Four deaths were reported; all were considered unrelated to DRV/r by the investigator


1. Centers for Disease Control and Prevention. HIV/AIDS surveillance report. Cases of HIV infection and AIDS in the United States and Dependent Areas, 2007, Vol. 19. Available from: http://www.cdc.gov/hiv/topics/surveillance/ resources/reports/2007report/pdf/2007SurveillanceReport.pdf. Accessed May 5, 2009
2. Centers for Disease Control and Prevention. HIV/AIDS among women. Available from: http://www.cdc.gov/hiv/topics/women/resources/factsheets/pdf/women.pdf. Accessed May 5, 2009
3. PREZISTA® (darunavir) Tablets. Full prescribing information. Available from: http://www.prezista.com/prezista/documents/us_package_insert.pdf. Accessed April 6, 2009
4. Johnson VA, et al. Top HIV Med 2008; 16(5): 138-145
5. Ortiz R, et al. AIDS 2008; 22(12): 1389-1397
6. Molina JM, et al. J Acquir Immune Defi c Syndr 2007; 46(1): 24-31
7. Clotet B, et al. Lancet 2007; 369(9568): 1169-1178
8. Madruga JV, et al. Lancet 2007; 370(9581): 49-58