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HIV+ Individuals Are Often Diagnosed Late in the Disease Stage
  ...The findings presented here have important implications for early detection strategies. Primary care providers and the public health community in general need to have continued dialogue with health care consumers regarding HIV infection, routinely inquire about and raise awareness of one's risk for HIV infection among patients and communities, and engage the patient and the public regarding readiness to test. If persons at risk for HIV infection are aware of their risk and can be encouraged to undergo testing before symptoms develop, HIV infection will likely be diagnosed before extreme CD4 cell depletion occurs and opportunities to prevent further transmissions are missed. In addition, as nearly one in four patients in our population tested negative for HIV at some point in the 5 years before testing positive, methods used in posttest counseling sessions to encourage safer sex need to be evaluated for effectiveness. Renewed efforts also are needed to encourage risk reduction strategies and serial testing for those persons with continued risky behaviors....
Highly active antiretroviral therapy has dramatically reduced the morbidity and mortality attributed to HIV infection and has changed the view of HIV disease in the Western world from that of an inevitably progressive and fatal infection to more of a chronic manageable condition. The potential benefits of early diagnosis include reduced transmission of infection, preservation of immune function, and prolongation of disease-free survival. Recent reports have found an inverse relationship between CD4 cell count at first diagnosis of HIV infection and virologic suppression once a highly active antiretroviral therapy regimen has begun. Other studies report that patients initiating therapy at a higher CD4 cell count have a better prognosis than patients who initiate therapy at a lower CD4 cell count. Current national guidelines for the treatment of HIV infection recommend that providers consider initiating highly active antiretroviral therapy for HIV-infected patients with CD4 cell counts of <350/[mu]L, and treatment is strongly recommended for patients with CD4 cell counts of <200[mu]/L.
Despite the potential benefits of early detection, a large proportion of newly diagnosed HIV-infected individuals are being identified late in the course of their infection, after profound immune depletion has occurred. It has been reported from various settings that 30%-40% of persons with HIV infection have already reached the point of immunologic AIDS-i.e., CD4 lymphocyte counts of <200/[mu]L-by the time HIV infection is diagnosed. We also know from previously reported studies that after primary infection CD4 cell counts decrease at an estimated rate of 60-100/[mu]L each year. This estimated rate of decline in the presence of HIV infection suggests that most HIV-infected individuals with CD4 cell counts <200/[mu]L at diagnosis have been infected for a decade or more.
Recommendations by the Centers for Disease Control and Prevention and others encourage screening more routinely for HIV infection, particularly in areas of high prevalence. Yet despite these recommendations, there is little indication that either the mean CD4 cell count or the proportion of patients with CD4 cell counts of <200/[mu]L at diagnosis have improved over time. In addition, several years after the Centers for Disease Control and Prevention issued recommendations for universal prenatal screening, it is estimated that only one half of pregnant women in the United States are tested for HIV.
There are several barriers to testing for HIV. Risk factors for acquiring HIV infection have been well established, and ways to improve HIV risk assessment skills have been described. However, limited time for provider/patient interaction and age-old taboos can prevent frank discussions of sexual practices between provider and patient.
The mechanics of testing for HIV are relatively simple, and rapid testing may make it easier for some populations to be tested and made aware of their results. However, testing for HIV typically involves informed consent, appropriate specimen collection, and some degree of posttest counseling (23). Studies have evaluated these mechanics as well as other possible barriers to testing. Improved counseling strategies may make testing for HIV more convenient and acceptable. Other work has been done to examine the social stigma and shame associated with HIV testing and infection, the denial of risk or an altered sense of risk, and the perception of life after testing positive for HIV. These factors no doubt contribute to delayed testing for and identification of HIV infection. Access to health care is likely an additional barrier to early diagnosis for some populations, but the prevalence of late testing among populations with good access to care has not been described.
There are also clinical factors that make early detection of HIV infection difficult. The signs and symptoms of acute HIV infection are not easily distinguished from other more common viral illnesses and can be dismissed by patients and providers alike. Aside from the acute phase of infection, several specific clinical conditions have been suggested as potential indicators of longer-term underlying infection, and it has been suggested that these indicators may be important prompts for testing. However, to our knowledge, no study has been performed to describe the frequency with which such prompts occur in the period preceding the diagnosis of HIV infection or to describe the extent to which CD4 cell depletion has already occurred when patients present with these indicators. Separately, aside from general associations with male gender and increased age, attempts to identify predictors of late testing have revealed few certainties.
The aims of this study, the HIV Early Detection Study of Unrecognized Positives, were to gain further insight into the problem of late testing for HIV in a setting where the problem of access to care is minimized and to potentially shed light on possible strategies for bringing about earlier detection. Our approach was to conduct chart reviews to examine all of the medical encounters between patients newly diagnosed with HIV infection and their medical care system in the years preceding diagnosis. Our setting, a closed, prepaid medical system with large numbers of newly identified cases of HIV infection, is one of few settings in which such a study is possible. This may explain why our search of the literature found no other work in this area.
Our primary research questions were as follows: Does ready access to medical care result in earlier detection of undiagnosed HIV-1 infection than what has been reported for general populations? How often are HIV risk factors and clinical indicators of possible post-acute HIV infection documented before diagnosis, and are they present before severe CD4 cell depletion occurs (in essence, what is the potential benefit of more vigilant attention to signs of possible infection)? What patient characteristics or other factors that predate a diagnosis of HIV infection are associated with lower CD4 cell counts at diagnosis?
Early detection of HIV infection improves prognosis and reduces transmission, but 30%-40% of cases are diagnosed late. A comprehensive and systematic review of medical encounters before diagnosis has not been done. This study reviews 5 years of medical encounters before the diagnosis of HIV infection in members of a large managed care organization where access to care is reasonably good. Patient characteristics, HIV risk factors, and clinical events preceding diagnosis were examined and tested for association with late diagnosis (CD4 cell count of <200/[mu]L at diagnosis). Of 440 HIV-infected patients, 62% had CD4 cell counts of <350/[mu]L, 43% had CD4 cell counts of <200/[mu]L, and 18% had CD4 cell counts of <50/[mu]L at diagnosis. Twenty-six percent of all patients had risks documented >1 year before diagnosis. Only 22% of patients had one of eight clinical indicators suggested in the literature as reasons to test for HIV >1 year before diagnosis. In multiple logistic regression, older age, male sex, race, risk group, no prior HIV testing, physician-initiated testing, and having any of eight clinical indicators before diagnosis were each associated with late diagnosis (p [le] .05). Late diagnosis remains a challenge despite good access to care. In our setting, effective risk assessment before symptoms arise offers greater potential for raising the mean CD4 cell count at diagnosis than does increased awareness of selected HIV-associated clinical prompts.
Separately, 26 patients (6%) had other AIDS-defining conditions at diagnosis (11 had Pneumocystis carinii pneumonia, 5 had Kaposi sarcoma, 5 had lymphoma, and 5 had other conditions). Only three patients who had AIDS-defining conditions (Kaposi sarcoma and lymphoma) at diagnosis did not also have immunologic AIDS.
Conversely, patients with decreased odds of having a CD4 cell count of <200/[mu]L at diagnosis were those who were female, those with a prior negative HIV test, and those who requested testing as opposed to the test being recommended by the clinician. Also in this model, the overall effect of race was associated with CD4 cell count at diagnosis at a level suggestive of significance (p = .05). This effect was driven in part by the subgroup of Asians who, despite having an unstable estimate due to the small number of patients in this subgroup, were the only individual race group to have a significantly increased risk of having a CD4 cell count of <200/[mu]L at diagnosis. Neither site size nor years of medical history available for review were associated with CD4 cell count at diagnosis.
Our data indicate that even among persons who have reasonable access to medical care and reside in geographic areas known for a high prevalence of HIV infection, where attention to the HIV epidemic is relatively high, nearly one half with newly diagnosed HIV infection had AIDS-defining CD4 cell depletion or another AIDS-defining condition at first diagnosis of HIV infection, and 62% had progressed to the point that national guidelines indicate that highly active antiretroviral therapy may be appropriate. This finding is in line with data reported from various other settings over the last 10 years (10-17) and suggests that reasonable access to care (i.e., care available to members enrolled in a large, integrated prepaid health plan) is not sufficient for early detection.
It is also apparent from both the data collected in this study and findings of other recently reported studies that despite recommendations to screen more routinely and to lower the threshold for testing, new cases of HIV infection were not being detected any earlier in 1998 than nearly a decade before.
Our data, in agreement with findings of previously reported studies, also indicate that increased attention to clinical indicators on the part of clinicians may lead to the earlier diagnosis of HIV infection in some patients. However, in our setting, the proportion of cases that might have been detected >1 year earlier as a result of more vigilant attention to clinical prompts to test for HIV was relatively small. Although 61% of patients had one or more of eight clinical indicators in the 5 years leading up to diagnosis, only 22% had these symptoms >1 year before diagnosis. Furthermore, our data indicate that aside from the clinical signs of acute infection, by the time patients present with clinical signs of possible HIV infection, CD4 cell counts have already fallen to levels warranting medical attention. Thus, increased attention to the clinical indicators studied here will not by itself lead to a substantially higher mean CD4 cell count at diagnosis. Our data suggest that this is true even when the population being served is at increased risk of infection.
Our finding that patients with undocumented HIV risks before diagnosis are more likely to have a CD4 cell count of <200/[mu]L at diagnosis is not surprising, since lack of documentation may reflect a lack of awareness of existing risks on the part of the provider or denial of those risks on the part of the patient. Regardless of the reason why risks were not documented, our finding that they were not underscores the need to perform an effective risk assessment and to document any risks so they can be further addressed by that provider or by other providers at subsequent visits.
The association between race/ethnicity and CD4 cell count at diagnosis was of borderline significance and was largely driven by the small subgroup of Asian patients. However, there are other data to suggest that there may be an association between race and a clinician's assessment of risk . Race deserves further study as a predictor of late testing, particularly with respect to patients of Asian descent. With regard to the association between who initiated testing and CD4 cell count at diagnosis, our data suggest that patients who recognize that they are at risk and actively seek testing are more likely to be diagnosed earlier than patients who are not tested until the clinician appreciates the situation and recommends testing.
JAIDS Journal of Acquired Immune Deficiency Syndromes 2003; 32(2):143-152 Daniel Klein; Leo B. Hurley; ÓDeanna Merrill; Charles P. Quesenberry Jr.; CHAIR (Consortium for HIV/AIDS Interregional Research). Kaiser Permanente Medical Center, Hayward, and áKaiser Foundation Research Institute, Division of Research, Oakland, California; and The Kaiser Permanente, Consortium for HIV/AIDS Interregional Research, Denver, Colorado, U.S.A.
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