Referenced Quotes about HIV/AIDS Tests and Measurements

Alberta Reappraising AIDS Society

David Crowe, President
Phone: +1-403-289-6609
Fax: +1-403-206-7717
Email: David.Crowe@aras.ab.ca

Roger Swan, Treasurer
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6
Canada
Office
Phone: +1-403-220-0129
Email: aras@aras.ab.ca
Web: noaids.ca

Referenced Quotes about HIV/AIDS Tests and Measurements

Negative HIV Tests with AIDS

There are many cases of people with AIDS defining conditions, or at least AIDS-defining low CD4 cell counts, who are continuously negative for HIV antibodies. How can this be if HIV is the undisputed cause of AIDS? It probably is not another virus, because these people are geographically scattered. Could it be that HIV is not the cause of AIDS, but most people with AIDS produce similar antibodies as a consequence of their illness?

“There is another, rarer, immunodeficiency syndrome well described, and I have seen it in my practice, of a case called, a disease called idiopathic CD4 T cell lymphopaenia. This is a rare immunodeficiency disorder in which individuals lack CD4 T cells, they are in very low numbers the CD4 T cells, and we don't know why it happens, the cause is still not determined, but all of those patients - and some of those patients can develop opportunistic infections. All of those patients have been studied very, very intensively to determine if they have HIV infection because, of course, initially it was thought that they had some unusual form of HIV and, with every investigation that's been undertaken, no-one can find HIV in them and they have very low CD4 T cell counts. So I think that is evidence that having a very low CD4 T cell count doesn't mean that you will develop HIV infection”
French MA. Testimony at Parenzee hearing. Court of Criminal Appeal. 2007 Feb
“I recently saw a 64 year old man with a skin lesion on his knee that had been intermittently weeping pus over the past four weeks and had been growing in size…Four days [after removing the growth] I was called by a consultant pathologist, who started quizzing me about this patient…The patient was homosexual, and when I told the consultant so it seemed to confirm his suspicion. 'This looks like a nodular Kaposi's sarcoma,' he said…From what I knew about Kaposi's sarcoma, it was nearly always linked to HIV infection [it is, in fact, an AIDS-defining condition]…I finally heard back from the consultant in London: 'Yes this has all the features of Kaposi's sarcoma'…Then, a week later, I received some unexpected news from the clinic…several HIV tests had been carried out, and all were negative”
Taubert M. The bad news and the bad news. BMJ. 2005 May 7;330.
“we describe a case of seroreversion [going from HIV-positive to HIV-negative] after the start of highly active antiretroviral therapy (HAART) during acute HIV infection, with seronegativity being sustained for almost one year, after which the patient discontinued drug therapy leading to an immediate increase in both the viral load and antibody titre.”
Jurriaans S et al. HIV-1 seroreversion in an HIV-1-seropositive patient treated during acute infection with highly active antiretroviral therapy and mycophenolate mofetil. AIDS. 2004 Jul 23;18(11):1607-8.
“We carried out a prospective study of total lymphocyte counts in 124 adult patients who were diagnosed with HIV (human immunodeficiency virus) infection and/or AIDS (acquired immune deficiency syndrome) and were admitted to Port Moresby General Hospital (PMGH) [in Papua New Guinea] from January to June 2003…An apparent 11% of the patients who had a clinical suspicion of AIDS were HIV-antibody-negative.”
Lavu EK et al. Total lymphocyte counts in adult HIV/AIDS patients in Port Moresby General Hospital. P N G Med J. 2004 Mar-Jun;47(1-2):31-8.
“This is a report of an HIV-1-infected child with absent HIV-specific antibodies, in whom the appearance of HIV-specific antibodies followed after the initiation of highly active antiretroviral therapy (HAART)…An 11-month-old girl with a history of oral candidiasis, anaemia and failure to thrive was hospitalized for dyspnoea [difficulty breathing], tachypnoea [rapid breathing] and diarrhoea. Pneumonia was diagnosed by chest X-ray. Blood cultures were positive for Salmonella typhimurium. HIV-1 infection was considered, and enzyme immunoassay and Western blot were performed; HIV-1-specific antibodies were not detected. Shortly afterwards the child was diagnosed with hypertrophic cardiomyopathy and referred to a tertiary centre. The diagnosis of HIV/AIDS was again considered, and HIV-1-specific polymerase chain reaction and p24-antigen tests were performed, which were positive…[after the child recovered from illness] HIV-1-specific antibodies could be detected for the first time after 6 months of therapy. The Western blot showed antibodies specific for gp24 and gp160…[our conclusion is that] This patient suffered from a rapidly progressive HIV-1 infection, with a striking absence of HIV-1-specific antibodies.”
Fraaij PL et al. Initation of highly active antiretroviral therapy leads to an HIV-specific immune response in a seronegative infant. AIDS. 2003 Jan 3;17(1):138-40.
“The presence of multiple diseases was common. Acute pyogenic pneumonia (population-adjusted prevalence 39·1%, 116/264), Pneumocystis carinii pneumonia (27·5%, 58/264), tuberculosis (18·8%, 54/264), and cytomegalovirus infection (CMV, 20·2%, 43/264) were the four most common findings overall. The three most frequent findings in the HIV-1-negative group were acute pyogenic pneumonia 50%), tuberculosis (26%), and interstitial pneumonitis 18%); and in the HIV-1-positive group were acute pyogenic pneumonia (41%), P carinii pneumonia (29%), and CMV 22%). HIV-1-positive children more frequently had P carinii pneumonia (odds ratio 5·28, 95% CI 2·12–15·68, p=0·0001), CMV (7·71, 2·33–40·0, p=0·0002), and shock lung (4·15, 1·20–22·10, p=0·03) than did HIV-1-negative children. 51/58 (88%) cases of P carinii pneumonia were in children younger than 12 months, and five in children aged over 24 months. Tuberculosis was common in all age groups, irrespective of HIV-1 status.Findings The presence of multiple diseases was common. Acute pyogenic pneumonia (population-adjusted prevalence 39·1%, 116/264), Pneumocystis carinii pneumonia (27·5%, 58/264), tuberculosis (18·8%, 54/264), and cytomegalovirus infection (CMV, 20·2%, 43/264) were the four most common findings overall. The three most frequent findings in the HIV-1-negative group were acute pyogenic pneumonia 50%), tuberculosis (26%), and interstitial pneumonitis 18%); and in the HIV-1-positive group were acute pyogenic pneumonia (41%), P carinii pneumonia (29%), and CMV 22%). HIV-1-positive children more frequently had P carinii pneumonia (odds ratio 5·28, 95% CI 2·12–15·68, p=0·0001), CMV (7·71, 2·33–40·0, p=0·0002), and shock lung (4·15, 1·20–22·10, p=0·03) than did HIV-1-negative children. 51/58 (88%) cases of P carinii pneumonia were in children younger than 12 months, and five in children aged over 24 months. Tuberculosis was common in all age groups, irrespective of HIV-1 status.”
Chintu C et al. Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study. Lancet. 2002 Sep 28;360(9338):985-90.
“investigation of this highly exposed yet HIV-1-uninfected cohort failed to reveal consistent HIV-1-specific cellular immune responses…The only well-documented marker of resistance, homozygosity for the CCR5 mutation delta32, did not account for the absence of infection, suggesting a multifactorial mechanism.”
Yang OO et al. Immunologic profile of highly exposed yet HIV type 1-seronegative men. AIDS Res Hum Retro. 2002 Sep 14;18(4):1051-65.
“The maintenance of seronegativity despite exposure to HIV has been observed in sexual partners of HIV infected persons, infants born to HIV-infected mothers, commercial sex workers and health care workers occupationally exposed to HIV-contaminated body fluids”
Makedonas G et al. HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity. AIDS. 2002 Aug 16;16(12):1595-602.
[The CDC National STD and AIDS Hotline Responds] The 1993 definition [of AIDS} also allows for HIV negative patients or those of undetermined HIV status to be diagnosed with AIDS when other causes for immunodeficiency are ruled out AND the person is definitively diagnosed with an AIDS Indicator Disease.”]
CDC. Questions about Case Definition [Email exchange with Michael Wright]. Personal Correspondence. 2000 Oct 4
“This report describes the field and laboratory investigation of eight patients who had clinical evidence of HIV infection, but repeatedly negative HIV-1 antibody screening results in the course of their clinical care. In all patients, HIV infection was proven [sic] by other diagnostic methods [PCR/viral load, p24 antigen and culture techniques]...Patient 2...HIV EIA result was negative during admission, but HIV infection was identified by HIV p24 antigen testing and DNA PCR...His wife was tested for HIV infection by HIV EIA and DNA PCR; the results of both tests were negative”
Sullivan PS, Schable C. Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. AIDS. 1999 Jan 14;13(1):89-96.
“A previously healthy 36-year-old male developed fatigue in early 1995. In April 1995, an EIA was negative for antibodies to HIV. He was admitted to the hospital in June 1995 for evaluation of a 27-lb weight loss, diarrhea, shortness of breath chills, headaches, myalgias, and right-upper-quandrant pain.…He was readmitted in August 1995…Gomori’s methenamine silver stain of an open lung biopsy yielded Pneumocystis carinii. The CD4/ lymphocyte count was 129/mm3, but an EIA [antibody test] and western blot assay [another kind of antibody test] for antibodies to HIV…were again negative…The patient had also been tested by EIA for antibodies to HIV while donating plasma multiple times between August 1990 and April 1994 at a plasmapheresis center. The records at the plasmapheresis center indicated that the patient had donated plasma 33 times during this interval, and an EIA was negative for antibodies to HIV each time…Assays for p24 antigen were weakly reactive, but because the reactivity was not neutralizable, the assay results were not clearly supportive of HIV infection…When subjected to base dissociation to disrupt immune complexes, the p24-antigen results became strongly reactive and neutralizable. HIV proviral DNA was also found in peripheral blood cells from the patient and his wife in a nested PCR (DNA-PCR) [these are extraordinary measures that would not have been taken if the patient had not had clinical signs interpreted as AIDS]
Reimer L et al. Absence of detectable antibody in a patient infected with human immunodeficiency virus. Clin Infect Dis. 1997 Jul;25(1):98-100.
“Patient A was a previously healthy, 31-year old homosexual man with a history of psoriasis who presented to his physician on 9 January 1995 with a 10-day history of fever, pharyngitis, dyspepsia [digestive problems], nausea, watery diarrhea, anorexia, sweats, and a generalized macular rash. He was not taking any medication…Result of HIV serology [ELISA, Western Blot, and testing for HIV-2 and HTLV-I] done on 13 February were nonreactive…Diagnostic HIV PCR perform on 28 March was positive, as were subsequent serum p24 antigen, HIV-1 coculture and HIV-1 plasma RNA quantitation assays. HIV-1 serologic testing remained negative. Patient A was hospitalized on 30 March and diagnosed with Pneumocystis carinii pneumonia [PCP] and esophageal cytomegalovirus infection…[he] had a continual decline in CD4 cell count, and subsequently died.”
Michael NL et al. Rapid disease progression without seroconversion following primary human immunodeficiency virus type 1 infection--evidence for highly susceptible human hosts. J Infect Dis. 1997 Jun;175(6):1352-9.
“The syndrome of idiopathic CD4+ T lymphocytopenia is defined by the Centers for Disease Control (1992) as cases which demonstrate depressed numbers (<300/cubic millimeter) and proportions (<20% of total T cells) on at least two consecutive occasions, with no laboratory evidence of HIV-1 or HIV-2 infection, and the absence of any defined primary or secondary immunodeficiency disease or therapy associated with depressed levels of CD4+ T lymphocytes...The patients have presented with a history of severe or recurrent infections with intracellular pathogens or virus-associated malignancies which, even before the description of AIDS, were recognised as being highly suggestive of underlying deficiency of cell-mediated immunity. Indeed, it was this constellation of clinical features...that clearly identified the new clinical entity of AIDS”
Bird AG. Non-HIV AIDS: nature and strategies for its management. J Antimicrob Chemother. 1996;37(Suppl B):171-183.
“In October 1995, the Utah Department of Health referred to CDC blood samples obtained from a man who had had onset of persistent fatigue and malaise during January 1995. During January-June 1995, he had sought medical care at several clinics. When he was admitted to a hospital in June because of respiratory illness and recent weight loss of 27 lbs, HIV-EIA was negative. In August, he was admitted with lung-biopsy-confirmed Pneumocystis carinii pneumonia (PCP) and a CD4+ count of 129 cells/microL; an HIV-EIA again was negative…Two blood samples obtained in October and in December 1995 were analyzed by CDC and the Food and Drug Administration (FDA). Both samples were weakly reactive for antibody (signal/cutoff ratio less than 2.2) when tested by the HIV-EIA kit from manufacturer A, but were negative by kits from manufacturers B and C. Because antibody detection assays were negative or weakly positive, additional assays were conducted. Assays for HIV-1 p24 antigen using the kit from manufacturer D on both samples were so weakly reactive that neutralization assays were invalid; however, after the samples were subjected to base dissociation to disrupt immune complexes, the p24-antigen results became strongly reactive and neutralizable. Antigen results also were positive using EIA kits from manufacturers E and F without immune complex disruption, including a positive neutralization test (kit E). HIV infection was diagnosed based on the positive p24-antigen test results.”
CDC. Persistent lack of Detectable HIV-1 Antibody in a Person with HIV Infection - Utah, 1995. MMWR. 1996 Mar 8;45(9):181-5.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00040569.htm#00001553.htm
“WHO case definition for AIDS surveillance

For the purposes of AIDS surveillance an adult or adolescent (>12 years of age) is considered to have AIDS if at least two of the following major signs are present in combination with at least 1 of the minor signs listed below, and if these signs are not known to be due to a condition unrelated to HIV infection.

Major signs

- weight loss >= 10% of body weight

- chronic diarrhoea for more than 1 month

- prolonged fever for more than 1 month (intermittent or constant)

Minor signs

- persistent cough for more than 1 month

- generalized pruritic dermatitis

- history of herpes zoster

- oropharyngeal candidiasis

- chronic progressive or disseminated herpes simplex infection

- generalized lymphadenopathy

The presence of either generalized Kaposi sarcoma or cryptococcal meningitis is sufficient for the diagnosis of AIDS for surveillance purposes.

Advantages of the WHO case definition for AIDS surveillance are that it is simple to use and inexpensive since it does not rely on HIV serological testing. Limitations of this case definition are its relatively low sensitivity and its low specificity particularly with respect to tuberculosis, since HIV-negative tuberculosis patients could be counted as AIDS cases because of their similarity in clinical presentation.

Advantages of the WHO case definition for AIDS surveillance are that it is simple to use and inexpensive since it does not rely on HIV serologic testing.”

WHO case definitions for AIDS surveillance in adults and adolescents. Wkly Epidemiol Rec. 1994 Sep 16;69(37):273-5.
“Stored serum samples from suspected AIDS/HIV-infected patients were obtained from Kisumu in western Kenya, Nairobi, and the coast seaport town of Mombasa. All these towns have the highest number of reported cases of AIDS in Kenya…A total of 913 samples were collected…A total of 265 samples were positive for HIV-1 as indicated by both ELISA and western blot for HIV-1”
Songok EM et al. Low prevalence of human T-lymphotrophic virus type I (HTLV-I) in HIV-positive patients in Kenya [letter]. J Acquir Immune Defic Syndr. 1994;7(8):876-7.
“The [Australian] National Centre in HIV Epidemiology and Clinical Research asked all specialists in clinical immunology and infectious diseases and other medical practitioners known to have an interest in immune disorders too provide information on any patient who had been diagnosed as immunodeficient on or after 1 January 1985 on the basis of a reduced CD4 lymphocyte count (no specific value was defined) or specific illnesses related to cell mediated immunodeficiency. The patients had to have had a negative result on serological testing for HIV-1 infection and congenital conditions and immunosuppressive treatment had to have been excluded…96 practitioners were contacted…12 case reports were submitted, of which seven satisfied the definition of idiopathic CD4 T lymphocytopenia with a CD4 lymphocyte count of <300 million/l or <20% of total lympocytes on more than one occasion. Supplemental tests (polymerase chain reaction and culture) for HIV-1 infection in three cases and tests for HIV-2 infection in four yielded negative results. Five patients had cryptococcosis…Only one patient gave a history of exposure to a factor associated with an increased risk of HIV infection: he had received multiple blood transfusions during 1982-3. CD4 lymphocyte counts six months after the diagnosis of immunodeficiency were available in all cases. In all except one CD4 lymphocytes as a percentage of total lymphocytes remained <20%. In three cases the absolute Cd4 lymphocyte count was >300 million/l. All seven patients were alive one year after diagnosis.”
McNulty A et al. Acquired immunodeficiency without evidence of HIV infection: national retrospective survey. BMJ. 1994 Mar 26;308(6932):825-6.
“We interviewed 31 of the 47 patients [hemophiliacs] identified with [HIV-negative AIDS, involving low immune cell counts (lymphocytopenia) and no record of positive HIV tests] and 23 of their contacts…19 persons had AIDS-defining illnesses (18 had opportunistic infections), 25 had conditions that were not AIDS-defining [except for their low CD4 cell counts] and 3 were asymptomatic…The investigation of contacts revealed no evidence of a new transmissible agent that causes lymphocytopenia.”
Smith DK, Neal JJ, Homsberg SD. Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. N Engl J Med. 1993 Feb 11;328(6):373-9.
“Recently, patients have been described with profound CD4+ T-lymphocytopenia [deficiency in CD4 immune cells] but without evident HIV infection...We studied 12 patients with CD4+ T-lymphocytopenia...(10 men and 2 women) [who] ranged in age from 30 to 69 years. Eight had risk factors for HIV infection. The clinical manifestations were heterogeneous: five patients had opportunistic infections, five had syndromes of unknown cause, and two had no symptoms. Two patients died from acute complications of their immunodeficiency.”
Ho DD, Cao Y, Zhu T et al. Idiopathic CD4+ T-Lymphocytopenia - Immunodeficiency without evidence of HIV infection. N Engl J Med. 1993 Feb 11;328(6):380-5.
http://content.nejm.org/cgi/content/short/328/6/380
“These four patients [described in this paper] have CD4+ T-lymphocytopenic immunodeficiency of unknown cause. Several lines of evidence strongly suggest that none are infected with HIV-1 or HIV-2. First, in contrast to the patients in the earliest reports of the acquired immunodeficiency syndrome (AIDS), none of our patients reported any of the major risk factors traditionally associated with AIDS, except Patient 1, whose last contact with prostitutes occurred several years before AIDS was first reported. Second, extensive searches for evidence of HIV-1 and HIV-2 infection were all negative. Third, in addition to CD4+ T-lymphocytopenia, all our patients had depletion of B cells, CD8+ T cells, or natural killer cells, or of all three types of cells, and three patients did not have the progressive depletion of CD4+ T lymphocytes that is characteristic of advanced HIV infection [but patient 1 did have a progressive decline, and patient 2 had such low values that a decline would be impossible, and patient 4 also had a decline, although perhaps not ‘progressive’]
Duncan RA et al. Idiopathic CD4+ T-lymphocytopenia--four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993 Feb 11;328(6):393-8.
“Our attention is now focused on the considerably large number of the seronegative group (135/227, 59%) who were clinically diagnosed as having AIDS. All the patients had three major signs [from the WHO’s so-called ‘Bangui’ definition of AIDS]: weight loss, prolonged diarrhoea, and chronic fever. Many of them also had other AIDS-associated signs, such as lymphadenopathy, tuberculosis, dermatological diseases, and neurological disorders.”
Hishida O et al. Clinically diagnosed AIDS cases without evident association with HIV type 1 and 2 infections in Ghana . Lancet. 1992 Oct 17;340(8825):971-2.
“Before the emergence of AIDS, disseminated infection with Mycobacterium avium intracellulare (MAI) was very rare…We report, as a further contribution to the debate on 'HIV-negative AIDS' a woman with disseminated MAI infection who was not infected with HIV and had no known primary or acquired immunodeficiency state…In 1980 this woman had had a blood transfusion (after an accident)…She had been repeatedly seronegative by ELISA and western blot for HIV-1, HIV-2, and HTLV-I/II, and tests for HIV-1 p24 antigen were negative; no reverse transcriptase activity or HIV-1 antigen was detected; and a polymerase chain reaction on fresh mononuclear cells and alveolar cells remained negative. In June, 1981, she deteriorated with persistent fever, severe weight loss, and an increase in pulmonary interstitial infiltrate. In September, 1991, an open lung biopsy was consistent with pulmonary alveolar proteinosis. Specific stains and cultures were negative for pathogens. She died in October, 1991.”
Couderc LJ et al. Disseminated Mycobacterium avium intracellulare infection without predisposing conditions. Lancet. 1992 Sep 19;340(8821):731.
“A 37-year old man presented with pruritus, night sweats, and cough. He denied risk factors for HIV infection. He had enlarged liver, spleen, and lymph nodes, but declined investigation for 6 months, by which time he also had anorexia, weight loss, productive cough, and breathlessness. His white cell count was 10,200/microliter (lymphocytes 600/microliter)…Biopsy studies revealed reactive lymph-node changes and pneumocystis carinii pneumonia (PCP). CD4, CD8 and Ig levels were low. Tests for HIV-1 and HIV-2 antibody, p24 antigen, and HIV env sequence were negative on two occasions. 9 months later he had an ulcerating lymph-node mass in the groin and hard, purple nodules over his trunk…tests for HIV (and HTLV-I) were again negative…The second patient was a 46-year-old male liver transplant recipient with a history of tuberculosis in childhood, legionella pneumonia, salmonella septiciemia, and recurrent shingles. He denied risk factors for HIV infection. His maintenance immunosuppression was prednisolone, azathioprine, and cyclosporin. 3 months after transplantation PCP developed. CD4 and CD8 counts were low but an HIV antibody test was negative…Over the next 6 months he had repeated bacterial pneumonia and cholangiitis [inflammation of the bile duct], multidermatomal shingles, and disseminated eczema herpeticorum. HIV antigen, antibody, and env sequence tests were negative.”
Kaczmarski RS et al. Idiopathic CD4+ T-lymphocytopenia. Lancet. 1992 Sep 5;340(8819):608; author reply 609.
“In 1984 we established a cohort of 965 intravenous drug users participating in drug treatment programmes in New Jersey and we have been following up this cohort with serological testes for HIV infection and lymphocyte subsets. 623 were HIV seronegative on study entry; and so far, 50 HIV seroconverters have been found. 106 men and 74 women have been HIV seronegative at all times and have had flow cytometry done at least once. For those studied more than once, we calculated mean CD4 counts and the CD4/CD8 ratios…3 men and 2 women in this HIV-seronegative cohort have CD4 counts below 500/microliter. All 5 are alive, and we have serial data confirming CD4 counts below 500/microliter for 3 of these patients, with different patterns exhibited. HIV-1 p24 antigen, HIV western blot, and HTLV serology are negative in all 3 and family histories are negative for diseases or syndromes associated with congenital immunodeficiencies.”
Weiss SH et al. Idiopathic CD4+ T-lymphocytopenia. Lancet. 1992 Sep 5;340(8819):608-9; author reply 609.
“Individuals presenting with opportunistic infections and/or low CD4 + cell counts but with no evidence of HIV infection were first described in 1985 and have been reported infrequently over the past few years.”
Moore JP, Ho DD. HIV-negative AIDS. Lancet. 1992 Aug 22;340(8817):475.
“One infant dying of histologically confirmed HIV encephalopathy was repeatedly seronegative”
Kind C et al. Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Eur J Pediatr. 1992;151:442-8.
“serologically negative blood of asymptomatic donors has been shown to transmit the virus [HIV]
Bruisten SM et al. Enhanced detection of HIV-1 sequences using polymerase chain reaction and a liquid hybridization technique. Application for individuals with questionable HIV-1 infection. Vox Sang. 1991;61:24-9.
“349 homosexual or bisexual men with biopsy proven KS seen in a university hospital-based dermatology practice between 1981 and 1989 were tested for antibodies to HIV-1, and 6 were HIV-1 negative. Case histories and laboratory data for the HIV-1 negative patients (pts) are presented. All patients were alive at December 21, 1989, with a median duration of disease of 60 mo (range 14 to 101 mo) from the date of diagnostic biopsy. 4 of these 6 patients gave histories of one or more sexually transmitted diseases, including gonorrhea (5), syphilis (4), herpes simplex virus (3), amoebiasis (2), and condyloma acuminata (1). Inhaled nitrite (poppers) use was reported by 5. Other workers have identified homosexual men with KS and no HIV infection.”
Friedman-Kien AE et al. Kaposi’s Sarcoma in HIV-negative men. Lancet. 1990;335(8682):168-9.
“The proportion of AIDS cases with HIV-antibody test results reported among cases meeting the pre- 1985 case definition (proportion tested) was 73% overall, but varied by area, being ³95% in 31 of the 54 states and territories, 85-95% in 19, and <85% in only 4: New York (39%), Massachusetts (59%), California (61%), and Illinois (76%). Between the last quarter of 1987 and the last quarter of 1988, the proportion tested increased in New York (from 33 to 47%), Illinois (73 to 87%), and overall (70 to 76%). The proportion tested was negatively correlated with the cumulative incidence of AIDS by area [i.e. the more AIDS in an area the less likely someone with “AIDS” was to have ever had an HIV test]
Selik RM et al. Impact of the 1987 revision of the case definition of acquired immune deficiency syndrome in the United States. J Acquir Immune Defic Syndr. 1990;3(1):73-82.
“9 infants (8%) were [HIV] seronegative [at 18 months] but had persistent or transient clinical signs [of HIV infection]…In 4 of 5 infants who had signs or symptoms of HIV infection after becoming seronegative, we detected evidence of HIV infection with use of hybridization studies carried out after the genome was amplified with the PCR method. 1 infant who became seronegative was totally free of symptoms but carried the HIV genome”
Blanche S et al. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. N Engl J Med. 1989 Jun 22;320(25):1643-8.
“Our data support the use of category I as a positive result [positive WB if 3 of 4 "key" bands are positive - this was the method used by FDA at the time]; however, if this were the only criterion that was finally established as unequivocal positive, more than 50% of patients with AIDS would be put into a ‘probable’ positive or indeterminate category. Our data support the inclusion of categories I, IIa and IIb as unequivocal positives [basically you need 2 of 4 key bands]. Applying these criteria would increase the percent positive for patients with AIDS to 79% without diminishing specificity [but note that 21% of AIDS patients would be HIV-negative!]
Lundberg GD. Serological diagnosis of Human Immunodeficiency Virus infection by Western Blot testing. JAMA. 1988 Aug 5;260(5):674-9.
“A 5-month-old white girl having persistent oral candidiasis was brought to medical attention because of acute respiratory distress, pneumonia, and hypoxia that worsened despite supportive care and antibiotics...The diagnosis of AIDS was suspected, although ELISA and Western blot tests were both negative for HIV antibody...The mother was HIV antibody positive by ELISA and Western blot but belonged to no high-risk group and was asymptomatic except for chronic diarrhea. The father was HIV antibody negative...The patient...remains HIV negative [after 6 months]
Goetz DW et al. Pediatric acquired immunodeficiency syndrome with negative human immunodeficiency virus antibody response by enzyme-linked immunosorbent assay and Western blot. Pediatrics. 1988;81:356-9.
“If laboratory tests for HIV were not performed or gave inconclusive results and the patient had no other cause of immunodeficiency…then any disease listed in Section I.B [including a variety of infections and cancers] indicates AIDS if it was diagnosed by a definitive method [as opposed to presumptive][Section III] With Laboratory Evidence Against HIV Infection [i.e. negative HIV tests] With laboratory test results negative for HIV infection a diagnosis of AIDS for surveillance purposes is ruled out unless: A. all the other causes of immunodeficiency listed above in Section I.A are excluded; AND B. the patient has had either: 1. Pneumocystis carinii pneumonia diagnosed by a definitive method; OR 2.a. any of the other diseases indicative of AIDS listed above in Section I.B diagnosed by a definitive method; AND b. a T-helper/inducer (CD4) lymphocyte count < 400/cubic millimeter] [i.e. AIDS can be diagnosed with a negative HIV test if no other reason for immunodeficiency is known, one of a specific list of illnesses is present (including PCP), and CD4 count is less than 400]
Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome. MMWR. 1987 Aug 14;36(1S):1S-15S.
http://www.cdc.gov/mmwr/pdf/other/mmsu3601.pdf
“Approximately one-third of AIDS patients in the United States have been from New York City and San Francisco, where, since 1985 [until 1987], less than 7% have been reported with HIV-antibody test results, compared with greater than 60% in other areas…[The 1987 definition is still valid today as it was incorporated by reference in the 1993 definition] A case of AIDS is defined as an illness characterized by one or more of the following ‘indicator’ diseases, depending on the status of laboratory evidence of HIV infection, as shown below…I. Without Laboratory Evidence Regarding HIV Infection. If laboratory tests for HIV were not performed or gave inconclusive results [e.g. indeterminate western blot or any test in a child under 15 months of age] and the patient had no other cause of immunodeficiency [steroid usage, etc.]…then any disease listed in Section I.B indicates AIDS if it was diagnosed by a definitive method [12 are listed including candidiasis, KS and PCP]…III. With Laboratory Evidence Against HIV Infection. With laboratory test results negative for HIV infection, a diagnosis of AIDS for surveillance purposes is ruled out unless: all the other causes of immunodeficiency listed above in Section 1.A are excluded; AND the patient has had either: [PCP] diagnosed by a definitive method; OR any of the other diseases of AIDS listed above…diagnosed by a definitive method; AND a T-helper/inducer (CD4) lymphocyte count <400/cubic mm.”
Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome. MMWR. 1987 Aug 14;36(S1).
http://www.cdc.gov/mmwr/pdf/other/mmsu3601.pdf
“Of 85 children with human-immuno-deficiency-virus (HIV) infection based on clinical (opportunistic infection), epidemiological (mother a drug addict or known to be HIV infected), and immunological (helper-T-cell deficiency and impaired proliferative response to pokeweed mitogen) features, 9 were found to lack antibody to HIV as measured by a commercial enzyme-linked immunoassay (ELISA). All 9 children had detectable levels of HIV antigen in simultaneous plasma specimens, measured by a sensitive antigen-capture ELISA. The use of the western blot assay and an ELISA with recombinant HIV antigens was able to identify HIV infection in 4 of the 9 children.”
Borkowsky W et al. Human-immunodeficiency-virus infections in infants negative for anti-HIV by enzyme-linked immunoassay. Lancet. 1987 May 23;1(8543):1168-71.
“We have seen an infant, born to seropositive parents, who was persistently seronegative for HIV antibody before the onset of severe immunodeficiency..The diagnosis of AIDS in this child rests on the opportunistic infections, decreased T4/T8 [immune cell] ratios, impaired T-cell immunity, loss of functional antibody, and seropositivity in the parents”
Marshall GS et al. AIDS in a child without antibody to HIV. Lancet. 1987 Feb 21;1(8530):446-7.
“only about 50% of European or North American patients with AIDS show detectable antibodies against one of either core proteins, more frequently p25 [now known as p24]
Montagnier L. Lymphadenopathy-Associated Virus: From Molecular Biology to Pathogenicity. Ann Intern Med. 1985 Nov;103(5):689-93.
“All but one of the 18 AIDS patients, a man with Kaposi’s sarcoma (KS) was found to be positive by IFA. He was also negative by ELISA and Western blot. A heterosexual man with KS [not considered AIDS, perhaps because only gay men are expected to get KS] also scored negative in all three tests”
Sandstrom EG et al. Detection of human anti-HTLV-III antibodies by indirect immunofluorescence using fixed cells. Transfusion. 1985 Jul;25(4):308-12.
“Among the 88 patients with AIDS tested, the HTLV-III [HIV] ELISA indicated a positive result in 72 cases (82%)”
Weiss SH et al. Screening test for HTLV-III (AIDS agent) antibodies: specificity, sensitivity, and applications. JAMA. 1985 Jan 11;253(2):221-5.
“Of the 32 AIDS patients, 14 had titers higher than 1/400, 7 had titers between 1/100 and 1/400 and 11 had titers between 1/40 and 1/100…In the control group, 2 had a titer higher than 1/400…and 3 had titers between 1/40 and 1/100…the significance of the higher rate of LAV seropositivity in hospitalized patients without AIDS but with tuberculosis or malaria and the significance of the correlation of seropositivity with lowered T4/T8 ratios and decreases of T4 lymphocytes are still unknown. [today these people would probably be classified as ‘AIDS’]
Brun-Vezinet F et al. Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS. Science. 1984 Oct 26;226(4673):453-6.
“Prevalence of antibodies to LAV [now known as HIV] p25 [now known as p24]…in serum from AIDS…patients and from control groups…AIDS patients…41 [% positive] LAS [swollen lymph nodes]…72 [% positive]…Controls…Homosexual men…1978…1 [% positive]…1980…24 [% positive] [the only group with ‘AIDS’ with more than 50% positive for p25 were gay men with Kaposi’s sarcoma at 63% positive]
Kalyanaraman VS et al. Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS. Science. 1984 Jul 20;225(4659):321-3.

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