Papers

HIV positive patients first presenting with an AIDS defining illness: characteristics and survival

^a Department of Genitourinary Medicine and Communicable Diseases, St Mary's Hospital Medical School, London W2 1NN, ^b Academic Department of Public Health, St Mary's Hospital Medical School, London W2 1NY

Correspondence to: Dr Poznansky.

Abstract

Objectives: To study the presentation and survival of patients who present with their first diagnosis of being HIV positive at the same time as their AIDS defining illness.
Design: Retrospective study of patients presenting with AIDS between 1991 and 1993.
Setting: Department of genitourinary medicine, St Mary's Hospital, London.
Main outcome measures: AIDS defining illness at presentation and survival after diagnosis of AIDS.
Results: Between January 1991 and December 1993, 97 out of 436 patients (22%) presented with their first AIDS defining illness coincident with their first positive result of an HIV test (group B). The remaining 339 patients (78%) had tested positive for HIV-1 infection within the previous eight years and had consequently been followed up in clinics before developing their first AIDS defining illness (group A). The two groups of patients did not differ in age and sex distribution, risk factors for HIV-1 infection, nationality, country of origin, or haematological variables determined at the time of the AIDS defining illness. However, the defining illnesses differed between the two groups. Illnesses associated with severe immunodeficiency (the wasting syndrome, cryptosporidiosis, and cytomegalovirus infection) were seen almost exclusively in group A whereas extrapulmonary tuberculosis and Pneumocystis carinii pneumonia were more common in group B. The survival of patients in group B after the onset of AIDS was significantly longer than that of patients in group A as determined by Kaplan-Meier log rank analysis (P=0.0026).
Conclusions: Subjects who are HIV positive and present late are a challenge to the control of the spread of HIV infection because they progress from asymptomatic HIV infection to AIDS without receiving health care. The finding that presentation with an AIDS defining illness coincident with a positive result in an HIV test did not have a detrimental effect on survival gives insights into the effects of medical intervention on disease progression after a diagnosis of AIDS.

Introduction

Previous studies have shown that the early detection of asymptomatic HIV-1 infection may lead to opportunities for the control of the spread of the infection and to interventions that may improve the prognosis for infected people.^{1 2 3 4} We identified a group of patients who presented with an AIDS defining illness who did not know that they were HIV positive and therefore had not received medical intervention in relation to HIV infection. We studied these patients to gain further insights into the effect of early medical intervention on the outcome of an AIDS defining illness.

Patients and methods

We retrospectively studied 436 patients who had presented to this hospital with an AIDS defining illness between 1 January 1991 and 31 December 1993. The patients were divided into two groups. In group A (339 patients) the time between the diagnosis of HIV seropositivity and the AIDS defining illness was greater than two months (range 2.1-120.2 months, median 46.1 months). In group B (97 patients) the time between a positive result in an HIV test and the AIDS defining illness was less than two months (range 0.0-2.0 months, median 0.0 months). Patients in group B had not been tested for HIV before developing their illness; seven of them received a clinical diagnosis of AIDS before an HIV test gave positive results, but the diagnosis was not confirmed for up to two months as a result of a delay in the completion of diagnostic tests such as culture of Mycobacterium tuberculosis in alveolar lavage specimens. One illness had precipitated the diagnosis of AIDS in all patients. Twelve patients had secondary AIDS defining illnesses, predominantly Kaposi's sarcoma.

The age at diagnosis of the first AIDS defining illness, sex, ethnic origin, country of origin, risk factors for HIV-1 infection, and the time between being diagnosed HIV positive and presentation with the AIDS defining illness was determined for each patient.⁵ The survival of patients until 31 December 1994 or death before this date was determined. Eight patients in group A and three patients in group B were lost to follow up after their AIDS defining illness. In addition, the following details were noted for the 305 patients presenting with their first AIDS defining illness during 1992 and 1993: the use of zidovudine or prophylaxis against Pneumocystis carinii pneumonia before the illness and haemoglobin concentration, mean red cell volume, neutrophil count, and CD4 positive T lymphocyte count at the time of the illness.

STATISTICAL METHODS

All categorical variables were compared between the two groups by Fisher's exact test. The survival time from the AIDS defining illness until death was compared between the two groups by Kaplan-Meier log rank analysis. The Mann-Whitney U test was used for comparison of all other continuous variables.

Results

Patients in group A did not differ significantly from patients in group B with respect to their age at presentation with their AIDS defining illness, sex, ethnic origin, the ratio of British citizens to non-British citizens, or risk factors for HIV infection (table I). Patients in group A did not differ from those in group B with respect to their haemoglobin concentration, neutrophil count, or CD4 positive T lymphocyte count (table II).

TABLE I--Patient characteristics. Values are numbers (percentages) of
 patients unless stated otherwise
---------------------------------------------------------------
                                     Group      Group B
                                    (n=339)      (n=97)
---------------------------------------------------------------
Sex:
  Male                              316 (93)     88 (91)
  Female                             23 (7)       9 (9)
Mean (SD) age (years):             37.8 (8.5)   38.3 (7.9)
Citizenship:
  British                           243 (72)     65 (67)
  Non-British                        96 (28)     32 (33)
Ethnic origin:
  White                             306 (90)     84 (87)
  Afro-Caribbean                     29 (9)      12 (12)
  Other                               4 (1)       1 (1)
Risk factors for HIV-1 infection:
  Homosexual/bisexual               261 (77)     77 (79)
  Heterosexual                       36 (11)     22 (22)
  Partner HIV positive               22 (6)       3 (3)
  Prostitute                          4 (1)         0
  Intravenous drug misuser           15 (4)         0
  Haemophilia                        1 (0.3)        0
---------------------------------------------------------------
Group A=patients unaware of HIV status at presentation with AIDS defining
illness; group B=patients knowing HIV status at development of AIDS
defining illness.

TABLE II--Haematological variables in patients at time of first AIDS
 defining illness in 1991, 1992, and 1993. Values are medians (ranges)
---------------------------------------------------------------------------
                                             Group A         Group B
                                             (n=236)         (n=69)
---------------------------------------------------------------------------
Haemoglobin (g/l)                         121 (60-166)     118 (71-169)
Mean cell volume (fl)                      95 (77-135)      90 (82-106)
Neutrophils (x106/l)                1.9 (0.2-7.8)    2.1 (0.6-16.4)
CD4 positive T lymphocytes (x106/l)  68 (0-460)       58 (20-410)
---------------------------------------------------------------------------
Group A=patients unaware of HIV status at presentation with AIDS defining
illness; group B=patients knowing HIV status at development of AIDS
defining illness.

Extrapulmonary M tuberculosis infection was diagnosed in 23 of the 339 (7%) patients in group A and in 15 of the 97 (15%) patients in group B (P=0.019, Fisher's exact test) (table III). The wasting syndrome, cytomegalovirus infection, and cryptosporidiosis were diagnosed in only three (3%) patients in group B but in 21 (6%), 31 (9%), and 17 (5%) patients, respectively, in group A (table III).

TABLE III--AIDS defining illness in patients. Values are numbers
 (percentages) of patients
-------------------------------------------------------------------------------
                                                    Group A        Group B
                                                    (n=339)        (n=97)
-------------------------------------------------------------------------------
Pneumocystis carinii pneumonia                      89 (26)        37 (38)
Kaposi's salcoma                                    44 (13)        20 (21)
Oesophageal candidiasis                             38 (11)         7 (7)
Cytomegalovirus infection                           31 (9)          2 (2)
Wasting syndrome                                    21 (6)          1 (1)
Non-Hodgkinson's lymphoma                           14 (4)          5 (5)
Mycobacterium tuberculosis infection                23 (7)         15 (15)
Cryptosporidiosis                                   17 (5)            0
Toxoplasmosis                                       14 (4)          4 (4)
Mycobacterium avium infection                        8 (2)          2 (2)
Other                                               40 (12)         4 (4)
-------------------------------------------------------------------------------
Group A=patients unaware of HIV status at presentation with AIDS defining
illness; group B=patients knowing HIV status at development of AIDS
defining illness.

A total of 305 patients presented with their first AIDS defining illness in 1992 and 1993 (236 patients in group A and 69 patients in group B). In group A, 115 (49%) patients were taking zidovudine and 147 (62%) were receiving prophylaxis against P carinii pneumonia before their illness. No patients in group B were receiving either treatment before their defining illness.

A Kaplan-Meier survival analysis was performed for patients presenting with new AIDS diagnoses between 1991 and 1993 (figure). Patients in group B survived longer with AIDS than patients in group A (P=0.0026, log rank analysis). The observed number of deaths during follow up was 209 in group A and 41 in group B. The expected number of deaths under the null hypothesis and with the size of the groups taken into account was 194 and 56 respectively.

View larger version (0K): [in this window] [in a new window]   Kaplan-Meier survival curves for patients with AIDS presenting early (group A) and late (group B)

Discussion

We identified a group of patients who presented with an AIDS defining illness at the same time as being found to be HIV positive; such patients thus develop AIDS before receiving health advice and medical intervention. Over one fifth of patients presenting with new AIDS diagnoses fell into this category between January 1991 and December 1993 despite there being a high profile HIV centre based in the Jefferiss Wing at St Mary's Hospital. A recent study reported that patients who were unaware of whether they were HIV positive up to nine months before being diagnosed as having AIDS were predominantly heterosexual, non-white, and aged between 15 and 24.⁶ In our study the two groups of patients did not differ in these respects. However, the criteria used to define late presenters were different in the two studies.

The pattern of AIDS defining illnesses differed between the two groups of patients. The incidence of P carinii pneumonia as the defining illness in patients in group A fell from 32% in 1991 to 16% in 1993, probably as a result of changing local prophylaxis guidelines from dapsone and pyrimethamine to co-trimoxazole.^{7 8} This is in contrast to the finding that the incidence of P carinii pneumonia in group B remained between 38% and 39% from 1991 to 1993. AIDS defining illnesses associated with severe immune deficiency such as the wasting syndrome, cryptosporidiosis, and cytomegalovirus infection were almost exclusively seen in group A.⁹ Conversely, there was an excess of AIDS defining illnesses associated with lesser degrees of immune deficiency in group B (particularly extrapulmonary M tuberculosis infection.) This may be because patients in group A presented with AIDS at a later stage in the decline of the function of their immune system than did those in group B. This is borne out by the finding that patients in group A who died within six months of presenting with an AIDS defining illness had lower CD4 positive T lymphocyte counts than patients in group A as a whole (P=0.007, Mann-Whitney U test). Paradoxically, the CD4 count at presentation with the others was higher, although not significantly, in patients in group A than in patients in group B (table III). The Concorde study suggested that a higher CD4 count attributable to the use of zidovudine during asymptomatic HIV infection was not associated with a clinical benefit.¹⁰

The survival of patients in group B, who presented late, was found to be significantly better than the survival of patients in group A, who presented early. This finding is consistent with the view that the onset of AIDS is delayed in patients who receive early medical intervention in HIV infection.^{10 11 12} However, the finding suggests that the subsequent survival of these patients when they develop AIDS may be commensurately decreased. We believe that our data are compatible with the results of the Concorde and other studies, in which early intervention with zidovudine delayed the development of AIDS but did not affect survival overall.^{10 12 13}

In conclusion, this study highlights the scale of the public health problem posed by patients presenting with AIDS coincidental with their first positive result in an HIV test. It also contributes to the debate on the effects of medical intervention on survival after an AIDS defining illness has developed.

We thank Dr Valerie Kitchen for insights into the data and Dr Geraldine A Johnson for her editorial assistance.

Source of funding: Department of Genitourinary Medicine and Communicable Diseases.

Conflicts of interest: None.

1. Rothenberg R, Woefl M, Stoneburner R, Milberg J, Parker R, Truman B. Survival with the acquired immunodeficiency syndrome: experience with 5,833 cases in New York City. N Engl J Med 1987;317:1297-302. [Abstract]
2. Bachetti P, Osmond D, Chaisson RE, Dritz S, Rutherford GW, Swig L, et al. Survival patterns of the first 500 AIDS cases in San Francisco. J Infect Dis 1988;157:1044-77. [Medline]
3. Drotman DP. Earlier diagnosis of human immunodeficiency virus (HIV) infection and more counselling. Ann Intern Med 1989;110:680-1.
4. Graham NMH, Zegger SL, Park LP, Phair JP, Detels R, Vermund SH, et al. Effects of zidovudine prophylaxis and pneumocystis prophylaxis on progression of HIV-1 infection to AIDS. Lancet 1991;338:265-9. [Medline]
5. Centers for Disease Control. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR 1987;36(suppl 1): 3-15S.
6. Porter K, Wall G, Evans B. Factors associated with the lack of awareness of HIV infection before diagnosis of AIDS. BMJ 1993;307:20-3.
7. Coker RJ, Nieman R, McBride M, Mitchell DM, Harris JRW, Weber JN. Co-trimoxazole versus dapsone-pyrimethamine for prevention of Pneumocystis carinii pneumonia. Lancet 1992;340:1099.
8. Peters BS, Beck EJ, Coleman DJ, Wadsworth MJH, McGuinness O, Harris JRW, et al. Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS. BMJ 1991;302:203-7.
9. Hanson DL, Horsburgh R, Fann SA, Havlik JA, Thompson SE. Survival prognosis of HIV-infected patients. J Acquir Immune Defic Syndr 1993;6:624-9.
10. Concorde Coordinating Committee. Concorde: MRC/ANRS randomised double blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 1993;343:871-81.
11. Cooper DA, Gatell JM, Kroon S, Clumeck N, Millard J, Goebel F-D, et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ counts greater than 400 per cubic millimeter. N Engl J Med 1993;329:297-303. [Abstract/Free Full Text]
12. Volberding PA, AIDS Clinical Trials Group of the NIAIDS. The duration of zidovudine benefit in persons with asymptomatic HIV infection. Prolonged evaluation of protocol 019 of the AIDS clinicala trials group. JAMA 1994;272:437-42. [Abstract/Free Full Text]
13. Oddone E, Cowper P, Hamilton JD, Matchar DB, Hartigan P, Samsa G, et al. Cost effectiveness analysis of early zidovudine treatment of HIV infected patients. BMJ 1993;307:1322-5.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    Twitter    What's this?

This article has been cited by other articles:

• LIONG, S Y, SUKUMAR, S A (2009). An African woman presenting with acalculous cholecystitis and sclerosing cholangiopathy. Br. J. Radiol. 82: 699-703 [Full text]  
• Lane, B. R., Liu, J., Bock, P. J., Schols, D., Coffey, M. J., Strieter, R. M., Polverini, P. J., Markovitz, D. M. (2002). Interleukin-8 and Growth-Regulated Oncogene Alpha Mediate Angiogenesis in Kaposi's Sarcoma. J. Virol. 76: 11570-11583 [Abstract] [Full text]  
• Freedberg, K. A., Samet, J. H. (1999). Think HIV: Why Physicians Should Lower Their Threshold for HIV Testing. Arch Intern Med 159: 1994-2000 [Full text]  
• Samet, J. H., Freedberg, K. A., Stein, M. D., Lewis, R., Savetsky, J., Sullivan, L., Levenson, S. M., Hingson, R. (1998). Trillion Virion Delay: Time From Testing Positive for HIV to Presentation for Primary Care. Arch Intern Med 158: 734-740 [Abstract] [Full text]  
• Coker, R. J., Poznansky, M. C., Bach, P. B., Guerra-Romero, L., Vazquez, F. P., Macher, A. M., Goosby, E. P., Kitahata, M. M., Maxwell, C. L., Volberding, P. A. (1996). Physicians' Experience and Survival in Patients with AIDS. NEJM 335: 349-351 [Full text]  
• (1995). Does Early HIV Diagnosis Improve Survival?. JWatch Psychiatry 1995: 22-22 [Full text]  
• (1995). Early Intervention Fails to Prolong Post-AIDS Survival. AIDS Clin Care 1995: 7-7 [Full text]  
• (1995). Does Early HIV Diagnosis Improve Survival?. Journal Watch Dermatology 1995: 17-17 [Full text]  
• (1995). DOES EARLY HIV DIAGNOSIS IMPROVE SURVIVAL?. JWatch General 1995: 8-8 [Full text]