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Symptoms of HIV and AIDS

There are numerous symptoms associated with "HIV Infection" and "AIDS" but some of the information about them seems arbitrary or contradictory.

The quotes are classified as:

Kaposi’s Sarcoma (KS)

KaposiÕs Sarcoma, a skin disorder often referred to as a cancer, was one of the diseases that defined GRID (Gay Related Immune Deficiency) even thought it isnÕt an immune deficiency. It stayed an AIDS-defining disease when GRID was expanded to be about 30 different diseases. By 1994 it was widely agreed that there was no HIV in KS lesions and the new theory was that KS was caused by Human Herpes Virus 8 (HHV8) helpfully called KSHV. But still, despite having a cause other than HIV, KS remained an AIDS-defining disease.

“We retrospectively studied all consecutive patients followed between 1995 and 2007 in two dermatology departments [in Paris, France]…During the study period, about 300 new cases of Kaposi sarcoma in HIV-negative individuals were seen…On the basis of the [undefined] inclusion criteria, 28 patients were identified as eligible for this study…[the most prevalent characteristic recorded was that] 22 patients were homosexual [the use of drugs, such as poppers, was not measured, and obviously none of the subjects were using AIDS drugs]…None of our patients had CD4 lymphopenia [low count of this type of white blood cell]; mean CD4 cell count was 920 [quite high]
Lanternier F et al. Kaposi's sarcoma in HIV-negative men having sex with men. AIDS. 2008 Jun 19;22(10):1163-8.
“We retrospectively studied all consecutive patients followed between 1995 and 2007 in two dermatology departments [in Paris, France]…During the study period, about 300 new cases of Kaposi sarcoma in HIV-negative individuals were seen…On the basis of the [undefined] inclusion criteria, 28 patients were identified as eligible for this study…[the most prevalent characteristic recorded was that] 22 patients were homosexual [the use of drugs, such as poppers, was not measured, and obviously none of the subjects were using AIDS drugs]…None of our patients had CD4 lymphopenia [low count of this type of white blood cell]; mean CD4 cell count was 920 [quite high]
Lanternier F et al. Kaposi's sarcoma in HIV-negative men having sex with men. AIDS. 2008 Jun 19;22(10):1163-8.
“A 19-year-old man was diagnosed with HIV 3 months earlier, with a self-reported history of purple skin lesions that appeared 2 years before and spontaneously remitted. At diagnosis he had extensive nodal and mucocutaneos KS [Kaposi’s Sarcoma], with a CD4 cell count of 182 cells/ml (13%) and a viral load of 21 000 copies/ml. He started antiretroviral therapy with lamivudine, stavudine, indinavir and ritonavir…He experienced an initial flattening of the KS lesions after 52 days, and was hospitalized with fever, vomiting and diarrhoea. Based on the time between the initiation of HAARTand an increase in CD4 cell numbers at the onset of the symptoms (an increase of CD4 cell count from 182 to 322 cells/ml in 18 days, last viral load 1840 copies/ml), IRIS was diagnosed by his original attending physician, who prescribed prednisone 20 mg twice a day and the patient was discharged. After 2 weeks of prednisone, he experienced an explosive growth of mucocutaneous [internal skin] lesions, facial oedema [swelling] and haemorrhagic [bleeding] lesions in both eyes. He reported that he perceived the oral lesions growing in a matter of hours, and was referred to our institution. An emergency tracheotomy was performed, steroids were withdrawn and a first cycle of 2mg vincristine and 15 mg bleomycin was administered. He developed Streptococcus pneumoniae purulent otitis media and thrombocytopenia. He was discharged with a silver cannulae, oral amoxycillin and unchanged HAART. Three weeks later he was hospitalized with epistaxis and profuse bleeding of the exophytic lesion in the oral cavity. Antiretroviral therapy was stopped, platelet aphaeresis was transfused and 5 days later a second course of bleomycin and vincristine was administered. He was discharged with a marked remission of all KS lesions as well as of the lymphoedema. He resumed HAART 2 weeks later…In the present case, a life-threatening exacerbation of KS shortly after steroids were used to treat IRIS was seen. In other corticoid-related KS manifestations in the literature, the onset was not explosive nor life threatening, and all remitted by simply removing steroids. The potential additive effects of IRIS with steroid use in KS, contraindicates its use as an anti-inflammatory therapy”
Volkow PF et al. Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome. AIDS. 2008 Mar 12;22(5):663-5.
“Sera were obtained from 2103 South African individuals (862 miners, 95 sex workers, 731 female and 415 male township residents; mean age 33.2 years). All sera were tested for antibodies to KSHV [Kaposi’s Sarcoma Herpes Virus, believed by some to be the cause of this skin cancer or cancer-like condition]…, HIV, gonococcus, herpes simplex virus type 2 (HSV-2), syphilis and chlamydia. Information on social, demographic and high-risk sexual behavior was linked to laboratory data…Overall KSHV and HIV prevalences were 47.5% and 40%, respectively…No significant difference in KSHV infection was observed among the residential groups. KSHV was not associated with any of the STI or any measures of sexual behavior.”
Malope BI et al. No evidence of sexual transmission of Kaposi's sarcoma herpes virus in a heterosexual South African population. AIDS. 2008 Feb 19;22(4):519-26.
“Our institute focuses on chronic persisting viral infections, particularly retroviruses, such as HIV and the leukaemia viruses HTLV-1 and HTLV-2, but also include, to some extent, papilloma viruses that cause cervical cancers; herpes virus 8 [causes] Kaposi's sarcoma, it's a cancer named after a Hungarian physician [who lived] over 100 years ago. It's caused by herpes virus number 8…[Lawyer] In 1994 did you say that they [HIV proteins] have not been found in the tumour cells of Kaposi sarcoma? [Gallo] Sure that's true. I don't know if I said it in [1994]…It must have been in 1988 or '89…HIV is not the sine qua non of Kaposi's sarcoma. HIV markedly increases the incidence of it. Or the fungal diseases that occur in an immune [suppressed] person…[Lawyer] 'We have never found HIV DNA in the tumour cells of Kaposi tumour. In fact we have never found DNA in T cells'? [Gallo] T cells. What? In T cells?…Did you say T cells? I don't know where you are getting that from. Certainly in Kaposi's sarcoma DNA - the very first paper we published on molecular cells shows the T cells.”
“Tasmanian devils [a marsupial with a bad temper] could be suffering from an AIDS-like virus, say two respected scientists…the cancer ravaging Tasmania's icon species could be linked to a virus suppressing the immune system…[but the research of cytogeneticist Anne-Marie Pearse] did not discount a viral or environmental trigger…Cell-to-cell transfer of a cancerous cell is unknown in human pathology and virtually unheard of in the animal kingdom…she suspects a chemical in the environment may have caused a genetic change to spark an infectious cancer cell line in one, or a small number, of devils…'Because of the lesion's visual similarity with Kaposi's sarcoma in humans, a form of devil AIDS or devil HIV merits consideration,' [we are not making this up]
Bevilacqua S. Disease may be linked to AIDS. Sunday Tasmanian. 2006 Feb 5
http://www.themercury.news.com.au/common/story_page/0,5936,18044101%255E921,00.html
“The objective of this case series and literature review is to characterize the clinical course and prognosis of HIV-infected patients with Kaposi's sarcoma (KS) flare during immune reconstitution inflammatory syndrome (IRIS), a heterogeneous and sometimes fatal disorder of immune perturbation after initiation of highly active antiretroviral therapy (HAART). Medical records of 9 HIV-infected patients with KS flare after virologic and immunologic response to HAART were reviewed from a single institution. An additional 10 cases were abstracted by computerized search of the medical literature. In our single institution series, mean time to onset of KS flare was 5 weeks. Pretreatment mean CD4+ count was 190 cells/mm(3) and mean HIV viral load was 153,934 copies per milliliter. During flare, mean CD4+ count was 256 cells/mm(3) and mean HIV viral load was 1156 copies per milliliter. Similar aggregate results are represented in the literature. Six fatalities are reported, 4 from pulmonary KS and 2 from unrelated causes. Systemic chemotherapy universally led to tumor regression, but was administered in only 10 of 19 cases. In no instance was HAART discontinued. Onset of IRIS-associated KS flare is observed as early as 3 weeks, with most cases diagnosed within 2 months after immunologic and virologic response to HAART. Such a flare does not necessarily portend a poor prognosis. Even for those patients with rapidly symptomatic KS, early systemic chemotherapy is effective in suppressing IRIS-associated flare. Close clinical supervision is warranted for the KS patient initiating, changing, or resuming HAART. Particular vigilance is recommended for pulmonary involvement.”
Leidner RS, Aboulafia DM. Recrudescent Kaposi's sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. AIDS Patient Care STDS. 2005 Oct;19(10):635-44.
“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…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.
“A 33-year-old man was diagnosed with HIV-1 infection after a suicide attempt. This infection was acquired through homosexual contact. 3 years later he started therapy with zidovudine, lamivudine, and saquinavir because of falling CD4-positive cell counts, but he opted to discontinue treatment after a few months. A year later, he developed skin nodules on his left thigh and was diagnosed with Kaposi’s sarcoma, an AIDS-defining illness. His CD4-positive cell count was 389 cells per µL. He refused treatment for both his HIV infection and skin lesions. After 5 years, the Kaposi’s sarcoma progressed to include most of the upper left leg in a circumferential manner, with large nodules and infiltrated plaques, and prominent lymphoedema. Antiretroviral treatment was resumed with lamivudine, zidovudine, and nevirapine. Despite declining and eventually undetectable viral load measurements (<50 copies per mL) and a CD4-positive cell count of around 700 cells per µL the skin tumours progressed. He received six cycles of chemotherapy with doxorubicin (15 mg/m2) and three cycles of the liposomal preparation (20 mg/m2), without benefit. Radiotherapy with 10 MV photons (total dose of 22 Gy in 11 fractions) resulted in moderate perianal and groin radiodermatitis and proctitis. Further treatment with thalidomide or paclitaxel is currently being considered.”
Sanders CJ et al. Kaposi's sarcoma. Lancet. 2004 Oct 23;364(9444):1549-52.
“Human Herpes Virus-8 (HHV-8) is associated with Kaposi's sarcoma (KS) in patients with AIDS as well as in patients with endemic KS who are HIV-negative. Studies in the United States and Europe have found the risk of KS and HHV-8 infection to be higher in HIV-positive men who have sex with men than in persons who acquired HIV-1 by injection drug use or heterosexual contact. Although KS is very common among patients with AIDS in Western countries, occuring in ~20% of male subjects with AIDS who have sex with men, only 0.2% of 101,945 adult or adolescent patients with AIDS in Thailand who were reported to the Ministry of Public Health (Bangkok) during 1994-1998 had KS…[In our study] 240 participants (24.2%) were HHV-8 positive, 749 were HHV-8 negative, and 3 had indeterminate results…Among men, seroprevalence was higher among those who were HIV-positive, but among the women, the seroprevalence did not significantly differe according [to] HIV serostatus…HHV-8 sero-prevalence was highest among HIV-positive wives of HIV- and HHV-8-positive husbands [32.3%], followed by HIV-positive wives of HIV-positive- and HHV-8-negative husbands [26.1%], HIV-negative wives of HIV- and HHV-8-positive husbands, and HIV-negative wives of HIV-positive and HHV-8-negative husbands…Among the 102 HHV-8 seropositive women in our study, only 32 (31.4%) of their husbands were also seropositive for HHV-8, indicating that most of the HHV-8 infections in these women were not acquired from their husbands. In addition, we did not find associations between HHV-8 seroprevalence and history of STD, number of sex partners, frequency of sex, or length of cohabitation. Furthermore, the seroprevalence of HHV-8 increased as the age at first sexual intercourse increased, which is the reverse of what one would expect if HHV-8 was commonly transmitted through sex.”
Chen N et al. Seroprevalence of Human Herpesvirus 8 Infection in Northern Thailand. Clin Infect Dis. 2004 Oct 1;39(7):1052-8.
“Although the innate immune system is implicated in the control of Kaposi's sarcoma (KS), the risk of developing KS is not associated with the nadir [lowest] natural killer (NK) cell count, and NK cell counts do not significantly increase or decrease during KS resolution. KS-associated herpesvirus replication was not demonstrated in vivo or in vitro within NK cells, suggesting that NK cells do not contribute to the resolution of KS. Their role appears limited to events occurring during early infection.”
Stebbing J et al. Natural killer cells are not infected by Kaposi's sarcoma-associated herpesvirus in vivo, and natural killer cell counts do not correlate with the risk of developing Kaposi's sarcoma. AIDS. 2003 Sep 5;17(13):1998-2000.
“Conclusions: Among individuals with HIV-KSHV coinfection, KSHV viremia identifies a subgroup with extremely high risk for developing KS [but they conveniently neglect to mention that only 7 out of 24 HIV+ men with AIDS-associated KS were KSHV DNA positive. This is greater than HIV+ men without KS (2/46) but not terribly convincing for a supposedly causative association.]
Engels EA et al. Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDS-associated Kaposi's sarcoma. AIDS. 2003 Aug 15;17(12):1847-51.
“Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS (35.1% versus 5.9%) [i.e. most men with HHV-8 did not have KS, and some men without HHV-8 did]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0% versus 32.4%). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions, and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions. Men with high HHV-8 antibody titers were more likely to have KS, but were less likely to have new KS lesions or HHV-8 DNA in PBMC or oral fluids [i.e. antibodies appeared to protect against infection, yet antibodies are also used to define infection!]
Cannon MJ et al. Risk factors for Kaposi's sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus. AIDS. 2003 Jan 24;17(2):215-222.
“The overall seroprevalence of antibodies against HHV-8 [believed by some to cause Kaposi’s Sarcoma] for the [Spanish] blood donor population was 6.5% [out of 1699 serum samples]…as blood donors are selected for the absence of other infectious disease, this prevalence rate for antibodies against HHV-8 is probably the lowest estimate for the general population of Spain [even though the vast majority of these people do not have Kaposi’s Sarcoma][And, after showing that 86.7% of HIV+ homosexual men, 28% of HIV- homosexual men, 17% of heterosexual men attending STD clinics and 11.5% of IV drug users are positive]…In summary, we have shown that HHV-8 is not a ubiquitous virus [huh? It’s in a significant population of the ‘not at risk’ population throughout Spain] that its distribution reflects that of KS [even though KS is rarely found in the general population]and is consistent with sexual transmission [and consistent with a lot of other things too!]…Nevertheless, some epidemiological descriptive findings require further clarification: despite the high prevalence of HHV-8 among homosexual men only a very small fraction will eventually develop KS, this fraction being even smaller among other transmission groups; regardless of HHV-8 prevalence, KS has a clear male preponderance in all of them”
Gambus G et al. Prevalence and distribution of HHV-8 in different subpopulations, with and without HIV infection, in Spain. AIDS. 2001 Jun 15;15(9):1167-74.
“HHV-8 [Human Herpes Virus 8, also known as Kaposi’s Sarcoma Herpes Virus] in [a group of gay, HIV-negative men] was similar to that in the general population (0-8%), and lower than the 30-37% seroprevalence noted...in HIV-1-infected homosexual men in the MACS [study] [There is no mention of cases of Kaposi’s Sarcoma, even though this virus is supposed to cause this disease]
Wang QJ et al. Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. Blood. 2001 Apr 15;97(8):2366-2373.
“in KS, KSHV/HHV8 and HIV-1 could share the responsibility for a high prevalence of this tumor, the KSHV/HHV8 being the etiologic agent and the HIV-1 representing the critical cofactor determining the epidemiologic characteristics. A key question remains unanswered: Why does HIV-1 not appear to increase the level of endemicity of KSHV/HHV8 as tested by the prevalence of KSHV/HHV8 antibodies?”
de The G et al. Prevalence of Human Herpesvirus 8 Infection Before the Acquired Immunodeficiency Disease Syndrome-Related Epidemic of Kaposi's Sarcoma in East Africa. J Natl Cancer Inst. 1999 Nov 3
“Kaposi's Sarcoma (KS)-associated herpesvirus or human herpesvirus-8 likely plays an important role in KS pathogenesis because KSHV seropositivity precedes KS and KSHV DNA is found in almost all KS lesions, whether or not there is a coexisting human immunodeficiency virus infection...KSHV infection in tumor tissue or in lymphoma-derived cell lines is predominantly latent”
Ballestas ME, Chatis PA, Kaye KM. Efficient Persistence of Extrachromosomal KSHV DNA Mediated by Latency Associated Nuclear Antigen. Science. 1999 Apr 23;284:641-4.
“In the present study, HHV-8 seroprevalence was investigated in HIV-seronegative subjects by an immunofluorescence assay to detect antibodies to both latent and lytic HHV-8 antigens. In general, we found a high HHV-8 seropositivity (64%) rate for HIV-seronegative age- and sex-matched control subjects from central and southern Italy. When HIV-seronegative KS patients from the same regions were analyzed, a 100% seropositive rate was determined.”
Cattani P et al. Human Herpesvirus 8 Seroprevalence and Evaluation of Nonsexual Transmission Routes by Detection of DNA in Clinical Specimens from Human Immunodeficiency Virus-Seronegative Patients from Central and Southern Italy, with and without Kaposi’s Sarcoma. J Clin Microbiol. 1999 Apr;37(4):1150-3.
“HHV-8 antibodies are highly prevalent in Egyptian children, suggesting that, in developing countries, HHV-8 infection may be acquired early in life through routes other than sexual transmission. The lower seroprevalence of HHV-8 relative to that of the other herpesviruses suggests that HHV-8 is less transmissible than other common herpesviruses…Anti-lytic and anti-latent HHV-8 antibodies were detected in 44.7% and 8.5% of the study participants, respectively. The prevalence of anti-lytic antibodies tended to increase with age, exceeding 50% in children older than 6 years…Egypt appears to be a country with a low incidence of KS. KS represents less than 1% of all the cancers diagnosed in the country and a minority of all skin tumors.”
Andreoni et al. High seroprevalence of antibodies to human herpesvirus-8 in Egyptian children: evidence of nonsexual transmission. J Natl Cancer Inst. 1999 Mar 3;91(5):465-9.
“One factor ties together the four epidemiological forms of KS [Kaposi's Sarcoma] – the novel herpes virus KSHV (or HHV-8), invariably found in KS tissues. If, as evidence suggests, HHV-8 is not ubiquitous, then its consistent presence in KS must indicate a key etiological role, which in turn would imply that the four forms of KS [including one that is HIV-associated] are indeed one, but with different (but unknown) augmenting cofactors. It is also clear, however, that in itself, HHV-8 is a very low risk factor for KS development. To illustrate: Most reports suggest a 2 to 10% global prevalence rate for HHV-8, with much higher rates in some areas. Assuming a 5% prevalence rate of HHV-8 in the United States and a 1970s baseline incidence of KS in men in the United States (about 0.3 cases per 100,000 men) the HHV-8 rate would be one case of KS in every 17,000 HHV-8 infections. The opposite trend is true for HIV-1, which is clearly not needed to cause KS, in that three of the four epidemiological forms of KS occur without HIV-1. Nonetheless, HIV-1 infection is associated with an enormous increase (by a factor of 20,000 to 50,000) in the incidence of KS in the presence of HHV-8.”
Gallo RC. The Enigmas of Kaposi's Sarcoma. Science. 1998 Dec 4;282:1837-9.
“Kaposi's sarcoma can occur in persons with a relatively intact immune system”
O'Brien SJ, Goedert JJ. HIV causes AIDS: Koch's postulates fulfilled. Curr Opin Immunol. 1996 Oct;8(5):613-8.
“Even among HIV-infected individuals, the risk for KS varies widely, with high rates observed in HIV-positive homosexual men and very low rates among HIV-infected hemophiliacs and children. These and other data have suggested that a second, sexually transmitted cofactor may be involved in KS etiology or pathogenesis, an inference that is further sustained by the occasional occurrence of KS in HIV-negative homosexual men…genomic sequences of a novel herpesvirus, termed KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), have been identified in KS tissues by polymerase chair reaction…These sequences are found in virtually all AIDS-KS specimens, and in the majority of HIV-negative KS cases as well…Our data indicate that, unlike most herpesviral infections described to date, infection with HHV8 is not ubiquitous, at least as judged serologically. Rather, HHV8 seropositivity appears to be limited to a rather small proportion of the population. We emphasize that the assay employed here is a first-generation serologic test and is not maximally sensitive. For example, it detects infection in only 83% of AIDS-related KS cases even though virtually all [about 90%] such cases are KSHV infected as judged by PCR detection of viral DNA in the KS tumor itself…Given the limited sensitivity of the test, the 1% prevalence we observe in the blood donor population is clearly a minimal estimate…Our serologic results contrast sharply with a recent PCR-based survey of HHV8 DNA in semen samples from low-risk individuals. In that study 91% of the 33 donors tested were reported to have amplifiable viral sequences in semen.”
Kedes DH et al. The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nat Med. 1996 Aug;2(8):918-24.
“In the current papers [July 25, 1996 in NEJM and August 1 in Nature Medicine], Chang, Moore, and co-workers report that antibodies to putative KSHV proteins are common only among those with KS - and among people who eventually develop the disease. "This is essentially the last piece of evidence needed for proving causality," said Moore…But they have had trouble convincing other leaders in the field, including Robert Gallo, who thinks that HIV itself leads to KS. "Nothing rules it out," Gallo says. However, he adds, "these data are certainly not proof of causation." Among his reasons for doubt…is a recent report from Philip Browning of Vanderbilt University offering evidence that…the virus may be widespread in populations that don't develop KS.”
Cohen J. Reports bolster viral cause of KS. Science. 1996 Aug 2;273(5275):573.
“Corticosteroid therapy has been linked with increased risk of KS in both HIV-infected and non-infected patients…[this] is not in conflict with the purported role of the newly described Kaposi's sarcoma-associated herpes viruses (KSHV)”
Enwonwu CO et al. Elevated cortisol levels in whole saliva in HIV infected individuals. Eur J Oral Sci. 1996 Jun;104(3):322-4.
“Jon Cohen reports that Yuan Chang described a Kaposi's sarcoma-associated herpesvirus (KSHV)-infected KS cell line. Actually, we and our collaborators have identified a lymphoblastoid cell line from an AIDS-associated non-Hodgkin's lymphoma, but not a KS cell line. We also have not found long-established KS cell lines to be KSHV infected, which is in agreement with the findings of Robert Gallo and others. In vitro KS cell lines appear to initially contain KSHV DNA sequences that are rapidly lost during in vitro passage”
Moore PS, Chang Y. Kaposi's sarcoma findings. Science. 1995 Oct 6;270(5233):15.
“Recent evidence suggests the presence of a novel infectious agent in Kaposi’s sarcoma (KS). Two DNA fragments, KS330Bam and KS631Bam, with significant homology to gammaherpesviruses, are present in a very high proportion of KS tissues. In contrast, control tissues from non-acquired immunodeficiency syndrome (AIDS) patients without KS are largely negative. These sequences have also been identified in eight non-Hodgkin’s lymphomas (NHLs) occurring in human immunodeficiency virus (H1V)- positive individuals, all of which are body cavity-based lymphomas (AIDS-BCBLS).~ These lymphomas appear to represent a distinct group of B-cell NHLs with a strikingly similar and unusual constellation of clinical, morphologic, immunophenotypic, and molecular genetic characteristics that distinguishes them from the vast majority of AIDS-related lymphomas…Sequence analysis of the KS330Bam and KS631Bam fragments, as well as of cloned flanking regions,’ has shown homology to two viruses in particular: EBV” and herpesvirus saimiri (HVS).” Both of these viruses are members of the gammaherpesvirinae subfamily of herpesvirus, which members are characterized by their ability to replicate in lymphoblastoid cells.” The degree of homology, with amino acid identities in the range of 30% to 50%, is consistent with these sequences belonging to a novel member of the same family, which we refer to as Kaposi’s sarcoma-associated herpesvirus (KSHV)…We have strong circumstantial evidence in support of the hypothesis that KSHV sequences represent a portion of a novel human herpesvirus. However, we have not yet shown transmissibility of KSHV or the presence of KSHV virions.”
Cesarman E et al. In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood. 1995 Oct 1;86(7):2708-14.
“If HHV-8 is the cause of KS, said Gallo, "this would be the most unorthodox virus in nature." Gallo noted AIDS-KS is found almost exclusively in gay men and only rarely in women or injection drug users who are infected with HIV. Yet herpesviruses are famous for spreading freely throughout populations. Gallo is also concerned because his co-workers cannot find evidence of the virus in a cell line derived from an AIDS-KS tumor they have shown cann cause KS-like lesions in mice. "The problem for us is very serious," said Gallo, who argues that HIV itself might play a central role in causing KS…Oncologist Parkash Gill…said he has failed to find DNA sequences from KSHV in 11 KS cell lines…NCI epidemiologist Robert Biggar, [was] enthusiastic about the early evidence but now [has] doubts about the virus…Biggar's doubt stems largely from a 27 May [1995] Lancet paper that describes how researchers…found evidence of KSHV in various skin lesions…This evidence runs counter to the notion that KSHV is unique to KS. "Suddenly we've found the cause of all cancers," Biggar scoffed.”
Cohen J. Controversy: is KS really caused by new herpesvirus?. Science. 1995 Jun 30;268(5219):1847-8.
“Our results suggest that KSHV [Kaposi’s Sarcoma Herpes Virus] is associated with lesions other than KS in non-AIDS immunocompromised patients”
Rady PL et al. Herpesvirus-like DNA sequences in non-Kaposi’s sarcoma skin lesions of transplant patients. Lancet. 1995 May 27;345(8961):1339-40.
“We have done skin biopsies in 16 patients, 14 were HIV negative (1 immunosuppressed patient, 10 classic KS, and 3 endemic KS) and 2 had AIDS-associated KS. Homologous normal skin was obtained in 9 HIV-negative patients…PCR amplification of HHV-like sequences was done with KS 330/233 primers…KS 330/233 sequences were detected in KS lesions from all patients tested and in normal homologous skin in only 3 of 9 patients, but were not detected in PBMC from the 5 patients tested. Only 3 of 6 primary cultures were positive. Of these 3 positive samples, 2 remained positive until the second passage. 4 other cultures were negative at the second passage. All cell cultures were negative at the third passage (n=8) and at the fourth passage (n=9).”
Lebbe C et al. Kaposi's sarcoma and new herpesvirus. Lancet. 1995 May 6;345(8958):1180.
“Extensive investigations, however, have not demonstrated an etiologic [causative] association between [CMV, Hepatitis B, HHV6, HIV and Mycoplasma penetrans] and AIDS-KS. Noninfectious environmental agents, such as nitrite inhalants, also have been proposed to play a role in KS tumorigenesis…20 or 27 (74%) of AIDS-KS DNA specimens hybridized with [DNA found in other KS tumors]…In contrast to AIDS-KS lesions, only 6 of 39 (15%) non-KS tissues from patients with AIDS hybridized [leading the authors to conclude that this DNA represents a virus that causes KS]
Chang Y et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9.
“In KS lesions of AIDS patients, Columbia's Yuan Change, Patrick Moore, and their co-workers report…they found DNA sequences that appear to be from a new herpesvirus [later called HHV8 or KSHV][but] questions center on Change and Moore's claim that the new herpesvirus is found only rarely-if at all-outside gay men…The Columbia group biopsied KS tissue from 27 patients who died of AIDS and found that 25 had unique DNA sequences that appear to be from the herpesvirus family. In comparison, those sequences turned up in only 6 of 39 non-KS tissues from AIDS patients and none of 85 non-KS tissues from people without AIDS.”
Cohen J. Is a new virus the cause of KS?. Science. 1994 Dec 16;266(5192):1803-4.
[the author quotes Robert Gallo as saying] [What I found reasonable was Peter Duesberg's] concept to combine virus with certain chemicals like poppers in the monkey model, because that's KS [Kaposi's Sarcoma]. KS, there is no question, is multifactoral. KS, there is no question, is enormously augmented by HIV, but clearly it's multifactoral. We've been arguing that from the beginning. We know that. You don't just take HIV and get Kaposi's sarcoma”
Hoke F. Robert C. Gallo looks beyond NIH and defends the past. The Scientist. 1994 Nov 14;8(22):12.
“Compared with all other AIDS patients…homosexual men were seven times more likely to have Kaposi's sarcoma”
Parekh BS et al. Dynamics of maternal IgG antibody decay and HIV-specific antibody synthesis in infants born to seropositive mothers. The NYC Perinatal HIV Transmission Study Group. AIDS Res Hum Retro. 1993 Sep;9(9):907-12.
“Thirty-nine patients who have not had a transplant have been reported to have KS associated with corticosteroid therapy…The authors studied 10 patients with the appearance of KS during corticosteroid therapy (6 men, 4 women; age range, 42-79 years)…Most patients had received prednisone, one had received triamcinolone, and one had received betamethasone and methylprednisolone…The interval between initiation of steroid therapy and appearance of KS lesions ranged from 3 months to more than 36 months…4 patients experienced complete regression of the KS lesions: in one after steroid withdrawal, in one after steroid withdrawal and radiation therapy, in one with no change in steroid dosage, and in one with radiation therapy. 4 patients experience partial regression after reduction or withdrawal of steroids. In two patients there was no progression after reduction of the steroid dosage. One of the patients who had a partial regression…exhibited progression of the lesions after reinstitution of steroid therapy…The true nature of KS, whether hyperplasia [abnormal skin cell growth] or neoplasia [cancer], remains controversial. Rapidly progressive forms of KS suggest a malignant process, as does the histopathology of the advanced tumor stage. Conversely, early lesions do not exhibit features of malignancy, and the fact that KS lesions are composed of multiple cell types does not support the concept of a monoclonal neoplastic process and the multicentric origin of KS. Our observations on spontaneous remissions in our patients after withdrawal of corticosteroids make it difficult to accept KS as a truly neoplastic process. However, although most reports showed absence of aneuploidy in AIDS-related KS and African endemic-type KS, we observed aneuploidy in most cases of steroid-induced KS.”
Trattner A et al. The appearance of Kaposi sarcoma during corticosteroid therapy. Cancer. 1993 Sep 1;72(5):1779-83.
“Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency.”
Barillari G et al. Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression. Implications for AIDS-Kaposi's sarcoma pathogenesis.. J Immunol. 1992 Dec 1;149(11):3727-34.
“The causal agent of Kaposi’s sarcoma is unknown. That the disorder is 10 times more common in homosexual or bisexual men with AIDS than in other HIV transmission groups suggests that a certain aspect of their behaviour exposes them to the agent or facilitates its spread...Sexual practices in which there was contact with partner's faeces before AIDS developed were the main determinants of Kaposi's sarcoma risk. Risk increased with frequency of insertive "rimming" (oral-anal contact): Kaposi's sarcoma developed in 18% of the men with AIDS who reported never having practised insertive rimming compared with 50% who practised it less than once a month, 73% between once a week and once a month, and 75% or more once a week (two-sided exact p-value for trend less than 0.001)....The men with Kaposi's sarcoma also tended to be more sexually active and were more likely to engage in other sexual activities that entailed contact with faeces than were the men who had other features of AIDS only.”
Beral V et al. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet. 1992 Mar 14;339(8794):632-5.
“Use of poppers was not significantly related to Kaposi’s sarcoma. Popper use was related to insertive rimming: about half the men who had never used poppers or had used them less than once a month reported practising insertive rimming, whereas most (20/26) of the men who used poppers at least once a week also practised insertive rimming. Stratification of the data by insertive rimming shows that there is no trend at all in Kaposi’s sarcoma risk with frequency of popper use [but flaws in this analysis include self-reporting of drug use (usually under-reported), a control comparison with other people with other AIDS diseases rather than with the general population, an overall high usage of poppers (30 out of 65) compared to rare usage in the general population, and no estimate of the total lifetime exposure to poppers (just current usage). Only 6 people studied claimed never to have used poppers (less than 10%) and more than half used poppers more than once a month]
Beral V et al. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet. 1992 Mar 14;339(8794):632-5.
“This difference [between time to AIDS in gay men versus hemophiliacs] largely disappears when Kaposi sarcoma (KS) is eliminated as an AIDS-defining illness, as KS occurs almost exclusively in gay men and often at a level of immune dysfunction less severe than seen with AIDS-associated opportunistic infections.”
Blattner WA. HIV epidemiology: past, present, and future. FASEB. 1991 Jul;5(10):2340-8.
“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.
“For Kaposi’s sarcoma, the annual rate among cohort members without AIDS rose from 1.6 cases/1000 persons in 1981 to 12.9 cases/1000 in 1987. However, because of the larger increase in other AIDS-associated diseases during these years, the percentage of Kaposi’s sarcoma cases has steadily declined to 61% in 1982, 48% in 1983, 44% in 1984, 30% in 1985, 29% in 1986, 27% in 1987, 23% in 1988, and (to date) 25% in 1989 [drug use was extremely high among this cohort, both in those with and without KS]
Lifson AR et al. Kaposi’s Sarcoma in a cohort of homosexual and bisexual men. Epidemiology and analysis for cofactors. Am J Epidemiol. 1990 Feb 13;131(2):221-31.
http://aje.oxfordjournals.org.ezproxy.lib.ucalgary.ca/cgi/reprint/131/2/221.pdf
“Among persons with AIDS the percentage with Kaposi’s sarcoma ranges from 1% in haemophliac men to 21% in homosexual or bisexual men…People born in Caribbean and African countries whose HIV was acquired by heterosexual contact had the next highest risk, 6% having Kaposi’s Sarcoma…Nitrite inhalants (poppers) or other substances to which homosexual men have been preferentially exposed have been suggested as a cause of Kaposi’s Sarcoma. The use of poppers is highly correlated with behaviours that provide opportunities for acquiring sexually transmitted infections. Kaposi’s sarcoma has been associated with both sexual practices and the use of poppers…The occurrence of Kaposi’s sarcoma in children and elderly people with parenterally transmitted HIV and in one-tenth of AIDS patients in Africa, where poppers are not used, suggests that poppers cannot account for the pattern of occurrence of Kaposi’s sarcoma in AIDS patients [but then, neither can homosexual practices such as rimming and fisting, which are presumably also rare in those groups!]
Beral V et al. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?. Lancet. 1990 Jan 20;335(8682):123-8.
“Although there is a clear correlation between HIV-1 infection and the aggressive, epidemic form of AIDS-KS [Kaposi’s Sarcoma], no genomic sequences of HIV-1 or of any other virus have been detected in KS tissues.”
Salahuddin SZ et al. Angiogenic properties of Kaposi’s sarcoma-derived cells after long-term culture in vitro. Science. 1988 Oct 28;242(4877):430-3.
“The first sign that a new disease was afoot was the appearance of a rare cancer called Kaposi’s sarcoma among the “wrong” patients...James W. Curran of the CDC and his colleagues, who had been following the nascent epidemic, clearly favored the notion of a new infectious agent”
Gallo RC. The AIDS virus. Sci Am. 1987;256:45-6.
“Kaposi’s sarcoma is highly prevalent [in central Africa], and cases in children and young adults…similar to those…in homosexual men with AIDS were documented in 1971”
Saxinger WC et al. Evidence for exposure to HTLV-III in Uganda before 1973. Science. 1985 Mar 1;227(4690):1036-8.
“None of five Kaposi's sarcoma tissue specimens examined was positive for HTLV-III [HIV] DNA sequences…Southern hybridizations can detect less than one viral DNA copy per 10 cells, [therefore] we interpreted these data to indicate that the three Kaposi's sarcoma lesions did not contain HTLV-III sequences.”
Shaw GM et al. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165-71.
“For [Kaposi’s Sarcoma and PCP] cases, the median lifetime use [of nitrite inhalants] was 336 days, compared with 168 days and 264 days for clinic and private controls, respectively.”
Jaffe HW et al. National case-control study of Kaposi’s sarcoma and Pneumocystis carinii pneumonia in homosexual men: Part 1, epidemiologic results. Ann Intern Med. 1983 Aug;99(2):145-51.
“Patients [with Kaposi’s Sarcoma] reported significantly longer histories of ever having been exposed to chemicals or solvents at work (risk ratio = 7.5) [compared to matched patients without KS]...A number of significant differences between the two groups appeared, however, in self-reports of ever having used various recreational drugs, including amyl nitrite, ethyl chloride, cocaine, phencyclidine (‘angel dust’), methaqualone, and amphetamines, each of which was associated with a risk ratio of 4 or greater [i.e. patients with KS were at least 4 times more likely to have used each of these drugs, than those without]...Significant dose-response relationships were found for amphetamines, amyl nitrite, cocaine, and ethyl chloride, but not for phencyclidine or methaqualone”
Marmor M et al. Risk factors for Kaposi’s Sarcoma in homosexual men. Lancet. 1982 May 15;1:1083-6.
“During the past 30 months, Kaposi’s sarcoma (KS), an uncommonly reported malignancy in the United States, has been diagnosed in 26 homosexual men (20 in New York City, 6 in California).”
Kaposi’s Sarcoma and Pneumocystis pneumonia among homosexual men - New York City and California. MMWR. 1981 Jul 3;30(25):305-8.
“The rarity of familial cases [of Kaposi’s Sarcoma], even in the areas considered endemic, is of special interest.Between 1908 and 1955, only six instances of families with multiple cases of KS had been found, and since then only two other familial cases have been reported. In a review of 96 documented cases of KS seen at this center between 1949 and 1975, only one instance of multiple cases in a family was noted…Average survival time in the American series is reported to be eight to 13 years; however, there are also a number of reports of spontaneous regressions and survival up to 50 years in the literature…An increased incidence of KS has also been reported in patients with disorders of the immune system such as immunodeficiencies, plasma cell dyscrasia, thymoma, or polymyositis. Also in 1974, Myers and coworkers observed two cases of renal transplant recipients who developed KS during the course of immunosuppressive therapy. The KS nodules regressed when immunosuppressive therapy was tapered down or discontinued. Several other reports also emphasize this correlation between the immunodeficiency states and the development of KS.”
Safai B, Good RA. Kaposi's sarcoma: a review and recent developments. CA Cancer J Clin. 1981 Jan-Feb;31(1):2-12.
“A rare neoplasm, disseminated visceral Kaposi’s sarcoma, appeared rapidly during the late rejection of a homograft kidney in a 35-year-old Negro woman. No evidence of tumor was present in the recipient prior to transplantation, and postmortem examination of the donor also revealed no neoplasia. Some features of Kaposi’s sarcoma suggest its similarity to neoplasms of the Burkitt’s type. It appears possible that immunosuppressant therapy may have permitted the development of this tumor in a transplant recipient.

Siegel JH et al. Disseminated visceral Kaposi's sarcoma. Appearance after human renal homograft operation. JAMA. 1969 Feb 24;207(8):1493-6.

Courtesy Alberta Reappraising AIDS Society, December 7, 2012.

© Copyright December 7, 2012 by Rethinking AIDS.