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  HIV DART 2008
Rio Grande, Puerto Rico
December 9-12, 2008
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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 at the time of the interim report, and the study dropout rate importantly highlights a very important domestic HIV issue that has been neglected: African-American women with HIV. 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. It also highlights the limitations and poor care overall in HIV. The GRACE Study was designed to provide additional scientific information related to treatment and care for women, and results from sub-studies are expected to be presented in the future when we will have a better opportunity to evaluate the study findings. I expect we will learn from these substudies. Of particular importance is what can we learn from this study that might lend itself towards improving care and treatment for African-American women. As an added benefit this gives us an opportunity to discuss the failings of the HIV care system for all with HIV. 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 'holidays' that are particularly inappropriate, appear more likely to drop out of care, may have poor relationships with their care providers, feel race impairs provider relationship & impacts care they receive (ICAAC '08), have more personal problems that interfere with optimizing care and treatment, and face additional barriers compared to men and other patient groups. A study presented at ICAAC found African-American women eligible for HAART were less likely to receive it according to WIHS study results reported at ICAAC. African-American women may have more fractured families.
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 if 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 impairments. Perhaps the clinic or care provider feel overwhelmed and is unable to spend the extra time to adequately help this patient. Perhaps the clinic service provision system intended to help such patients, the case manager etc, is incapable or underfunded. Perhaps when such a patient is referred to see a case manager or other type of support service the patient never shows up; she needs to be 'handed off' to the other service provider. It appears that better quality service provision is needed for African-American women. I argue that services provided for all HIV patient populations are inadequate, it is just that African-American women are particularly impacted by the poor quality of these services because they need better services than others due to having more needs and facing more barriers than others.
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. In fact the HIV care system is inadequate and lacking for all, and getting worse. 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 Ryan 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, and so is the private care system which is also beset by severe limitations imposed by private insurance carriers. Why can't we provide additional needed financial support to both the private and public systems.
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 needs and barriers for patients. This includes private office care to. All patients ought to be provided an opportunity to optimize their success with care and treatment. To do this Federal officials need to do 2 things -- provide more money and redesign the system, both private and public care, in a way that addresses and prioritizes important barriers and problems and whereby patients can receive high quality HIV care. After AIDS HCV coinfection is the leading cause of death in HIV. HCV coinfection affects/infects mostly African-Americans and Latinos, and fact that HCV coinfection mostly impacts the highly disadvantaged African-American and Latino patient communities and IVDUs is a key to the high death rates caused by HCV coinfection. I wrote the HCV language that was inserted into the Ryan 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. Many of the very same issues and barriers discussed here apply to the diverse Latino communities and often they have additional barriers related to culture and language and other problems. How often does a patient hear from their HIV doctor that their ALT, liver enzyme levels, are normal so they do not have a problem with hepatitis C, 'they can postpone treatment'. And this patient does not receive further attention or a liver biopsy. The advice is incorrect and puts that patient at serious risk for HCV disease progression, cirrhosis, and death. In fact, 25% of patients can have normal ALT and still have advanced liver disease that calls for consideration of therapy. This scenario may not happen as often as it used to because awareness about HCV has improved but it still occurs. As well, other inappropriate scenarios like this occur which prevent HCV coinfected patients from receiving proper care and timely treatment. The reasons for this situation are either the doctor/care provider was not well educated about HCV, the doctor did not want to spend the time explaining the situation to the patient, the doctor was overwhelmed with their patient load, and a support system to properly educate the patient was not in place.
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. When any patient visits their HIV care provider today, in private or public care, the amount of time is often limited to 15 minutes of discussion about the patient's situation before the doctor quickly ushers the patient out the door. HIV is a very complex disease and considering we have an entire legislative program, one billion dollars from the Ryan White Care Act, and immense stakes tied to addressing HIV, why is it that we are providing such inadequate HIV care? Doctors and the entire HIV care system are stretched as far as they can be, it is immensely underfunded. Doctors are leaving care and going to work for drug companies, and this has been going on for years. The reason these problems affect African-American women more is because they have more issues, more barriers, and problems that stand between them and realizing optimal care and successful therapy. Today the patient with the best opportunity to achieve success is the one who is well educated and/or completely dedicated to achieving these goals. But these inadequacies in the care system affect all patients regardless of the patient's education and economics. It is just that when patients see their doctor they may not realize how much their care is severely cut and limited. We have come to the point where now the doctor's time is constricted by the need to be totally consumed with how much income is needed to make a profit or to run the clinic. The clinic or doctor is reimbursed by how many patients they see and not rewarded but is dis-incentivized for providing better care and spending more time with the patient. That is why the patient gets 15 minutes, why the doctor may not have the time to comprehensively address the patient's needs. Today care is much more complicated than prescribing HAART. Today actually a patient may need more time than in the past because the disease related issues have been expanded to importantly have to consider many comorbid conditions including diabetes, heart disease, bone disease, aging, bone disease, and neurological conditions in addition to discussion about the HAART regimen and when to begin therapy or when to switch to another regimen if the patient has HIV drug resistance. How many care providers are well qualified at interpreting HIV drug resistance reports they receive from a lab? A patient with extensive drug resistance in a large public inner urban city hospital may not get the advice and support they need in selecting the proper regimen and the support needed to understand their situation. What about bone disease? The rates of bone loss are very high among HIV+ individuals. Are doctors prepared for this, for the most part they are not. They are not educated about this problem, they don't screen patients for this. And patients are not educated about this. Reimbursement for bone-dexas is not generally available, we don't have guidelines or recommendations for screening and care.. Proper screening and testing is not performed in HIV offices today although studies report 60% of HIV+ individuals have osteopenia and at the stunning average age of 45 yrs old. Unfortunately the research community, HHS guidelines committee members, and government officials are not effectively addressing bone disease in HIV either.
There is an important context for the ethnic disparities in HIV care experienced by African-Americans and Latinos 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, and particularly African-American women. 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 aging 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 research findings are interpreted properly, we need to make sure further research is funded, and we need to characterize and implement interventions. But ethnic disparities in HIV care may predict who lives longer with HIV. It is important to continue conducting HIV research studies in women of color so we better understand the barriers to good care and identify solutions, raise awareness about important issues and conduct good science to improve health and longevity. Jules Levin
Safety, 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.
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). HIV DART 2008, December 9-12, 2008, Rio Grande, Puerto Rico. Abstract 34.