The outcome of HIV infection is divided into four stages (or groups) according to the Centers for Disease Control (CDC) (Table 23.1), and it is not yet clear what factors determine whether (or how rapidly) movement occurs from one stage to the other.
After the initial seroconversion, which is often associated with a febrile mononucleosis-like illness, patients who are HIV antibody-positive enter either group 2 (chronic asymptomatic infection) or group 3 (persistent generalized lymphadenopathy).
Persistent generalized lymphadenopathy, or extended lym-phadenopathy syndrome, should be diagnosed only if enlarged lymph nodes in at least two extrainguinal sites have been present for 3 months. There is no evidence that progression into group 4 is different in these patients from those without node enlargement. Biopsy is not now routinely undertaken but may be necessary to exclude lymphoma or Kaposi's sarcoma in a node that suddenly enlarges or, occasionally, in pyrexia of unknown origin, to exclude infection with acid-fast bacilli.
Three histological patterns have been described in biopsies of lymph nodes from HIV antibody-positive patients. Type I is the most common pattern seen in persistent generalized lymphadenopathy in which there is follicular hyperplasia with or without paracortical hyperplasia. The germinal centres are greatly expanded and may show necrosis and haemorrhage (Figure 23.1a). There is a variable loss of surrounding mantle zone lymphocytes. Type II is also seen in persistent generalized lymphadenopathy but is less common and may herald the development of AIDS. There is diffuse lymphoid hyperplasia with loss of germinal centres. Type III pattern, seen in patients with established AIDS, is marked by the absence of lymphoid follicles and severe depletion of both T and B lymphocytes (Figure 23.1b).
Infection with HIV is associated with a range of haematological abnormalities. The mechanisms for these changes are multiple: quantitative and qualitative marrow defects and immune cyto-penias are a direct result of HIV infection, whereas the effects of opportunistic infections, lymphoma and a myriad of drugs against infection, malignancy or HIV itself play an important role. With such a varied assault on the haemopoietic system it is not surprising that peripheral blood and bone marrow abnormalities are common in HIV infection and increase in frequency with advancing disease.
Cytopenia is common in HIV disease and is often associated with morphological abnormalities in peripheral blood and bone marrow cells suggestive of myelodysplasia. It is likely that HIV directly affects marrow production either by direct infection of precursor cells or by infecting stromal or accessory cells, thereby inducing altered production of regulatory cytokines.
Studies of purified haemopoietic progenitors (CD34+), as well as haemopoietic colonies obtained from semisolid culture, have yielded conflicting results with respect to the presence of HIV DNA, although HIV infection of monocytes/macrophages, promonocyte cell lines, megakaryocytes and eosinophils has been demonstrated as well as infection of bone marrow-derived fibroblast cell lines. Although susceptibility of marrow progenitor cells to infection by HIV in vitro has been demonstrated, the extent to which progenitor cell infection in vivo contributes to
Table 23.1 Stages of HIV infection according to the Centers for Disease Control (CDCI classification).
CDC 1 Recently observed illness with seroconversion (1)
CDC 2 Well, no generalized lymphadenopathy (2)
CDC 3 Well, with generalized lymphadenopathy (3)
CDC 4A Significant constitutional disease (ARC or AIDS)
Fever or night sweats for over 1 month (ARC) (4) Weight loss > 10% (ARC) (5) Diarrhoea for over 1 month, no cause (ARC) (6) "Wasting syndrome (AIDS) weight loss and diarrhoea, or fever and weakness for over 1 month (7)
CDC 4B Neurological
CDC 4C1 Infections in AIDS
*Pneumocystis carinii pneumonia (15) "Cerebral toxoplasmosis (16) *Cryptosporidiosis over 1 month (17) "Oesophageal Candida (18) "Bronchial Candida (19) "Cryptococcosis (20)
* Mycobacterium avium complex (MAC) (21)
*CMV retinitis (22)
*CMV oesophagitis (23)
*CMV colitis (24)
*CMV pneumonitis (25)
*Other proven CMV (26)
"Mucocutaneous HSV over 1 month (27)
CDC 4C1 "Progressive multifocal leucoencephalopathy
(PML 29) "Isosporiasis (30) "Histoplasmosis (31) "Coccidioidomycosis (32) "Extrapulmonary TB (33) "Pulmonary TB (46) "Recurrent salmonella septicaemia (34) "Recurrent bacterial chest infections (73)
*Pneumocystis carinii pneumonia (37) "Cerebral toxoplasmosis (38) "Mycobacteriu-avium complex (MAC), only AFB+ (39) "Oesophageal Candida (40) PCP - recent symptoms, abnormal chest radiograph, Pao2 < 9.3 and no bacterial pathogen
CDC 4C2 Infections in ARC
Oral hairy leucoplakia (43) Shingles, multidermatomal (44) Nocardis (45) Oral Candida (47)
Diagnosed by definitive method "Cerebral lymphoma (50) "Kaposi's sarcoma (51) "Non-Hodgkin's lymphoma (52) "Invasive cervical carcinoma (78)
Diagnosed presumptively "Kaposi's sarcoma (55) "Cerebral lymphoma (66)
CDC 4E Possible HIV-associated disease (not AIDS)
Constitutional (not ARC or AIDS) Fatigue (59)
Intermittent diarrhoea (60) Intermittent fevers/sweats (61) Weight loss < 10% (62)
Presumptive CMV disease (66)
Salmonella, septicaemia - one episode (69)
Amoebic dysentery (74)
Other infections (75)
CDC 4E Neoplasms
Hodgkin's lymphoma (76) Invasive anal carcinoma (77) Other neoplasms (79)
HZV, shingles, one dermatome (87) Facial warts (88)
Non-genital molluscum contagiosum (89) Other skin (90) Fungal toenail dystrophy (91) ZDV nail dyschromia (113)
Aphthous ulcer (94)
Angular stomatitis/cheilitis (95)
Sinusitis, chronic (96)
Otitis externa, chronic/recurrent (97)
Thrombocytopenia, idiopathic = < 20 (100) Thrombocytopenia 21-150 (101) Anaemia, no cause except HIV (104) Haematological other (105)
Aseptic meningitis (107) Guillain-Barre syndrome (108) Neurological other (109)
Cardiomyopathy (114) Cardiovascular other (115)
Sclerosing cholangitis (116) Other GI (117)
General other Arthralgia (102) HIV myopathy (103) Splenomegaly (111) ZDV myopathy (112) Primary gonadal failure (118) Endocrine other (119) General other (120)
"Denotes AIDS diagnosis. A CD4 count < 200 without an AIDS defining illness is considered as an AIDs diagnosis in the USA (but not in Europe).
Number in brackets is the diagnosis code.
abnormal haemopoiesis is uncertain, and it is likely that the effect of HIV on stromal or accessory cells is more important. Infection of marrow accessory cells, T lymphocytes, macrophages, fibroblasts and dendritic cells with HIV leads to overproduction of cytokines, such as tumour necrosis factor (TNF), interleukin 1 (IL-1) and interferons, which have inhibitory effects on marrow progenitor cells. In vitro infection of stromal cells leads to impaired colony growth. T-cell depletion of marrow enhances marrow colony production in HIV-infected patients and, when T-cell-depleted marrow is cocultured with increasing concentrations of circulating or marrow T cells, an inverse correlation of T cells with progenitor colony growth is observed. This inhibitory effect of T lymphocytes is not seen in patients who are not infected with HIV.
Cell cultures of bone marrow from patients with HIV infection show a normal response to recombinant growth factors but colony formation is suppressed when anti-HIV antibodies are added to the culture system. This effect is not seen in marrow cultures from seronegative donors, suggesting that anti-HIV antibodies exert a suppressant effect directly on HIV-infected progenitor cells or indirectly on HIV-infected marrow accessory cells.
Was this article helpful?
Now if this is what you want, you’ve made a great decision to get and read this book. “How To Cure Yeast Infection” is a practical book that will open your eyes to the facts about yeast infection and educate you on how you can calmly test (diagnose) and treat yeast infection at home.