NATAP: GRACE Study/HIV Care for African-Americans

[Guest guest]

Women's

HIV Care and Treatment Access for African-Americans and the GRACE Study

 

Comment from Jules: There is

another perspective to interpreting the results from the women’s GRACE Study.

Following this commentary by me is the NATAP report written about the

presentation at the HIV-DART meeting just completed in Puerto Rico on the

interim GRACE Study results. And below this commentary is a link to the entire

interim dataset reported in the poster by the study investigators at the Mexico

City international AIDS conference. The interim results report about 25% of

women withdrew from the study, and final results will be reported at the

Capetown international AIDS meeting in 2009. But 75% stayed in the study, and

the study dropout rate importantly highlights a very important domestic HIV

issue that has been neglected: African-American women with HIV. So some might

say that keeping 75% of women in the study is an accomplishment. The GRACE

Study merely reflects the healthcare problems and barriers to receiving good quality

HIV care facing HIV+ African-American women in the USA. This also highlights

the ethnic disparities of healthcare in the USA facing African-Americans,

Latinos, and poor. The GRACE Study was designed to provide additional

scientific information related to treatment and care for women, results from

sub-studies should be presented in the future. I expect we will learn from

these substudies. More important is what can we learn from this study that

might lend itself to improving care and treatment for African-American

women.  The results from the GRACE

Study provide an opportunity to discuss these concerns further and hopefully to

evoke others to understand this problem and to mobilize to address it.

For African-American women

overall, care and access to care and treatment for HIV is not as good as that

compared to whites and less underserved patient communities. There are serious

care problems for African-American men and women but women carry a higher

burden and face more barriers than men. Part of this problem is also related to

HCV-coinfection care and treatment and is discussed below. Disparities of care

highlighted in  the GRACE Study and

reported in other studies are that African-American women take ‘drug holidays’

perhaps untimely ‘holidays’, appear more likely to drop out of care, may have

poor relationships with their care providers, and have more personal problems

that interfere with optimizing care and treatment, and face additional barriers

compared to men and other patient groups.

When an African-American

woman presents herself for care to a clinic she presents the person facing the

barriers related to race integrated into her life, the barriers and problems of

gender, the problems related to economics and housing, her educational

background and id she is a parent the problems related to parenting she faces,

and perhaps the problem of being a single parent raising a child and being at

the same time disadvantaged financially and educationally. HIV is often placed

by her in the context of -- which of these problems appears more important to

her, HIV may not appear as important to her as we think it should. Perhaps she

suffers from thinking she doesn’t deserve the best shot at life, at good

quality care. Perhaps she doesn’t think she deserves to live; perhaps drug

addiction caused mental, emotional, and physical disease. Perhaps the clinic or

care provider feels overwhelmed and is unable to spend the extra time to

adequately help this patient. Perhaps the clinic system intended to help such

patients, the case manager etc, is incapable or underfunded.

We have neglected these

problems. Attention has been fixed on addressing global HIV in black Africa,

while we have a serious problem facing African-Americans and Latinos here in

the USA, in New York, in the inner urban neighborhoods of our cities like

Washington DC, Baltimore, Detroit, Miami, Los Angeles, Oakland, Chicago, and in

the rural areas and urban areas of the South.

There is a potential

solution that is obvious, at least a pathway for addressing the issues.

Providing better and targeted support programs for African-American women, and

men, can address and provide some relief. The kinds of programs needed could be

discussed and designed separately from this report but are not that difficult

to figure out The real problem is finding the resolve to do this. We send

hundreds of millions overseas for global HIV but we have as big a problem here

that some of this money could be used for. I certainly agree we need to provide

assistance for global HIV in undeveloped nations but we have neglected the care

system in the USA. We spend about 1 billion dollars through the White Care

Act so why does the public, and for that matter the private care system,

provide such lousy care. The public HIV care system in the USA is overburdened

and underfunded.

The entire system is corrupt

in a sense that money and funding provides the key incentives for the people in

charge of running the individual hospitals and clinics. These individuals have

become beset with finding adequate funding for their clinics rather than being

able to focus on providing the care that patients require. The system should be

overhauled so that the goal is to provide improved care, care that addresses

the barriers for patients. All patients ought to be provided an opportunity to

achieve the same successful care and treatment many of us are lucky to have. To

do this Federal officials need to do 2 things -- provide more money and

redesign the system in a way that addresses and prioritizes important barriers

and problems. Besides AIDS HCV coinfection is the leading cause of death in

HIV. HCV coinfection affects/infects mostly African-Americans and Latinos, and

that is a key to the high death rates. I wrote the HCV language that was

inserted into the White Care Act with these thoughts in mind. Many ADAP

formularies have HCV therapy on the list but the uptake is very low. The reason

is because the patient communities most disproportionately impacted are

communities of color and poor people, patients who need the most support,

education and programs for support to better undertstand HCV disease and

treatment. These problems reviewed above apply also to Latino communities. Many

of the very same issues and barriers apply to the diverse Latino communities

and often they have additional barriers related to culture and language, and

others.

Private HIV care is also

overburdened and underfunded so care in this system is also seriously lacking.

These problems have been overlooked for years and continue to get worse and

build in magnitude, There is an important context for these ethnic disparities

in the problem of aging with HIV. For patients in the USA the 2 most important

issues today are ‘Aging with HIV’ and the problems of African-Americans.

African-Americans and Latinos have higher rates of some of the comorbid

diseases facing HIV+ individuals. Diabetes and heart disease, as well as

hepatitis C coinfection are more prevalent among African-Americans and Latinos

than whites in the USA. The good news is that the NIH recently released 3

Requests For Applications for ‘Aging & HIV’ studies. The ACTG recently held

a half-day plenary on integrating aging studies into their research agenda.

Conferences and workshops have been discussing these questions increasingly

this year. So progress is being made but we must closely monitor this to make

sure the research is implemented and implemented properly in that it asks the

right questions; we must make sure and then the research findings are

interpreted properly, we need to make sure further research is funded, and we

need  to characterize and implement

interventions.

Jules LevinSafety, Tolerability and Efficacy of Darunavir/Ritonavir in Treatment-Experienced Women With HIV Infection: 24-Week Interim Analysis of GRACE (Gender, Race, And Clinical Experience) - (08/07/08) Reported in Mexico City

Dropout

Rate in Study of US Minority Women Near 25% at 24 Weeks

HIV DART 2008, December 9-12, 2008, Rio Grande,

Puerto Rico

Mark Mascolini

Almost one quarter of

antiretroviral-experienced women enrolled in the GRACE trial of

darunavir/ritonavir dropped out of the study by week 24, but usually not

because of side effects and in only one case because of virologic failure. GRACE

(Gender, Race, and Clinical Experience) aimed to enroll minority women in the

United States and Puerto Rico and succeeded in recruiting a population that is

nearly two thirds African American and nearly one quarter Hispanic. The dropout

rate suggests the difficulties in treating a poor, often marginalized

population, even in a wealthy country. (from Jules: and the diffiulty of

completing a study in the patient population, particularly when there are so

many more treatment options available today as compared to years ago without

having to remain in a study).

The primary endpoint of

GRACE is the difference in virologic response (under 50 copies) between women

and men at week 48. Enrollees could have hepatitis B or C infection if the

condition was clinically stable and did not require treatment during the trial.

GRACE excluded people who had already used darunavir, etravirine, enfuvirtide,

tipranavir, integrase inhibitors, or CCR5 antagonists. All enrollees had taken

a regimen including a protease inhibitor (PI) or a nonnucleoside for at least

12 weeks.

All study participants began

twice-daily darunavir/ritonavir plus a background regimen selected by the

investigator. The trial provided etravirine (the newest nonnucleoside),

emtricitabine, tenofovir, fixed-dose tenofovir/emtricitabine, and zidovudine

but did not mandate their use. Participants could not take enfuvirtide,

tipranavir, integrase inhibitors, or CCR5 antagonists.(from Jules: perhaps some

women dropped out to access raltegravir).

A planned 24-week interim

analysis of this 65-site study involved 203 of 429 enrolled people who

completed 24 weeks of treatment or discontinued therapy. The 24-week population

included 180 women and 23 men. Their age averaged 42 years, 64% were African

American, and 21% were Hispanic. Among women, pretreatment viral load averaged

4.67 log (about 45,000 copies) and median pretreatment CD4 count measured 206

(range 1 to 868).

Most women--107 of 180 or

59.4%--had already taken two or more PIs. Of 173 women whose background regimen

was analyzed, 29 (17%) had no active background drugs, 45 (26%) had one active

drug, and 99 (57%) had two or more active drugs, not counting etravirine.

Fifty-nine women (33%) entered GRACE after a treatment interruption of 4 or

more weeks.

At the 24-week point, 44 women (24.4%) and 2 men (8.7%) had dropped out of the

trial. Fourteen women (32% of dropouts) and 1 man quit because of side effects,

and 1 woman stopped because of virologic failure. The remaining dropouts were

attributed to loss to follow-up (11 women, 25% of dropouts), protocol

violations (5 women, 11%), withdrawn consent (5 women, 11%), and other reasons

(8 women, 18%).

A

time-to-loss-of-virologic-response analysis figured a 50.5% sub-50-copy

response rate for women at week 24 (91 of 180 women). An analysis that excluded

women who dropped out for reasons other than virologic failure figured a 65.5%

sub-50-copy response rate (91 of 139 women). In a noncompleter-equals-failure

analysis, the average CD4 count among women rose by 86 cells through 24 weeks.

The investigators did not figure response rates separately for men because of

their low number. Eighty-two of 203 people (40%) in this analysis took

etravirine, but the investigators did not dissect responses according to

etravirine use or number of active drugs in the background regimen.

Thirty women (17%) had a serious adverse event, including 8 with pneumonia.

None of the 23 men in the interim analysis had pneumonia. The most common grade

2 to 4 adverse events possibly or probably related to study drugs in women and

men were nausea (5.9%), diarrhea (5.4%), rash (3.0%),

weight gain (3.0%), dizziness (2.0%), and dyspepsia (painful or difficult

digestion) (2.0%). Rates of these problems did not differ between women and

men. The most frequent grade 2 to 4 lab abnormality was hyperglycemia (in 16%

of women and 19% overall) and total cholesterol (in 12% of women and 13%

overall). Grade 2 to 4 AST elevations affected 6% of women (6.3% overall), and

ALT elevations affected 4% of women (6% overall).

The

investigators concluded that 24-week virologic response rates and adverse event

incidence in GRACE generally reflect those in earlier trials of

darunavir/ritonavir in treatment-experienced people. Although entry criteria

included "ability to comply with protocol requirements," that did not

prevent the 30 dropouts for reasons other than toxicity or virologic failure.

Carmen Zorrilla (University of Puerto Rico) noted that the target population

shoulders a heavy burden of sociologic problems and comorbidities such as

mental illness. In their effort to recruit high proportions of women and

minorities, trial planners sought out several sites with little experience in

clinical trials. Perhaps that inexperience translated into a diminished ability

to retain patients in the study. It would also be interesting to see how many

people who signed up for GRACE during a drug holiday quit the study before week

24.

 

Reference

1. Zorrilla C, Currier J, Squires K, Bridge DA. Safety, tolerability and

efficacy of darunavir/ritonavir in treatment-experienced women with HIV

infection: interim analysis of GRACE (Gender, Race, And Clinical Experience