Stages of HIV infection

• Stage 1- Laboratory confirmation of HIV with CD4 count >500/cmm. No AIDS defining conditions.
• Stage 2- Laboratory confirmation of HIV with CD4 count 200-500/cmm. No AIDS defining conditions.
• Stage 3- Laboratory confirmation of HIV with CD4 count <200/cmm or any one AIDS defining conditions.

AIDS defining conditions:

• Pneumocystis jeroveci infection
• Mycobacterium avium complex infection
• Mycobacterium tuberculosis infection
• Toxoplasmosis
• Candidiasis
• Histoplasmosis
• Cryptococcosis
• Cryptosporidiosis
• Leishmaniasis
• Cytomegalovirus disease
• Recurrent bacterial infections (>1 episode)
• Lymphomas
• Kaposi sarcoma
• Cervical cancer
• AIDS dementia complex
• Wasting syndrome

Hematological manifestations in HIV are due to

• Direct effect of HIV on hematopoietic tissue
• Immune dysregulation- 
  • Infected macrophages aberrantly release TNF alpha, TGF beta and IL1
  • Polyclonal B cell activation
• Complications of secondary infections
• Side-effects of medications- Most of the medicines used in HAART can cause cytopenia

Anemia with HIV

Seen in 70-80% patients

Causes:

• Decreased production
  • BM infiltration by lymphoma, Kaposi sarcoma etc
  • Infections- Mycobacterial, CMV, Parvovirus B19, Fungal infection
  • Drugs- Zudovudine, gancyclovir, Bactrim, amphotericin B
  • Direct damage- Viral infection of hematopoietic cells
  • Anemia of chronic disease
  • Nutritional anemia
• Increased destruction
  • Autoimmune hemolytic anemia
  • Hemophagocytic syndrome
  • TTP
  • DIC
  • Oxidant damage in G6PD deficiency

Treatment:

• Treatment of cause if found- Ex: IVIg for Parvoviral infection
• HAART therapy- Corrects anemia in most of the patients within 6 months. Mechanism of action is not known.
• Erythropoietin- 100-200Units/Kg- SC- 3 times a day. Then once a week once hemoglobin is between 11 and 12 gm/dL.

Neutropenia

Seen in 50% of patients

Causes:

• Infected macrophages aberrantly release TNF alpha, TGF beta and IL1 which suppress colony growth of GM-CFU
• Decreased G-CSF level
• Infections affecting BM
• HIV related myelodysplasia
• Medication induced- Zudovudine, ganciclovir, Bactrim

Treatment

• Treatment of cause if found
• HAART therapy- Improvement is seen in some of patients
• G-CSF- 5mcg/Kg, then titrate the dose as per the ANC

Thrombocytopenia

Seen in 40% of patients

Causes

• Primary HIV associated thrombocytopenia
  • Destruction of megakaryocytes as they also bear CD4 on the surface
  • Autoimmune destruction due to molecular mimicry between HIV GP 160/120 and platelet Gp IIb/IIIa
• Hypersplenism due to co-existing hepatitis/ cirrhosis
• Medications
• Marrow infiltration- malignancy, infections
• Thrombotic thrombocytopenic purpura

Treatment of Primary HIV associated thrombocytopenia

• Treatment of cause if found
• HAART therapy
• Interferon alfa
• High dose IVIg- Reserved for patients with active bleeding
• Splenectomy
• TPO agonists- Eltrombopag
• Glucocorticoids- Better avoided, as they enhance immunosuppression

Bone marrow aspiration changes in HIV

• Hyper/hypo/normo cellular
• Trilineage dysplasia
• Increased plasma cells
• Increased eosinophils
• Increased megakaryocytes
• Increased iron
• Sometimes granuloma
• Opportunistic infections
  • Mycobacterium avium
  • Cryptococcus
  • Toxoplasma
  • Leishmaniasis

Bone marrow biopsy changes

• Stromal changes- edema, gelatinous transformation
• Tumors- NHL, HL, Kaposi sarcoma, Castleman disease
• Increased reticulin

(For HIV associated lymphoma- Refer to chapter “Lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation”)