HIV Long case

Presentation
  • How the diagnosis was made
  • presence or absence of seroconversion illness
  • nature of confirmatory testing
Risk factors:
  • Sexual activities, injecting drug use, previous blood transfusions
Investigations
  • Note current CD4 count and viral load
  • Evidence of resistance on genotyping
  • Co-existant STIs such as hepatitis A, B, C
Complications
  • AIDS related
    • CD4 cell count: 200-500 cells/uL: Herpes zoster, pneumococcal pneumonia, oral candidiasis, tuberculosis
    • 50-200 cells/uL: pneumocystis jiroveci, pneumonia, CNS toxoplasmosis, Cryptococcus, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, primary CNS lymphoma
    • < 50 cells/uL: disseminated mycobacterium avium complex, CMV retinitis, cryptosporidiosis
  • Non AIDS related co-morbidities
    • accelerated atherosclerosis an interplay between traditional risk factors
    • active ongoing inflammation 
    • HIV virus itself - causes 2 fold increase CVD risk
    • HIV related neurocognitive effects eg HIV associated dementia, peripheral neuropathy
    • HIV associated nephropathy - usually a collapsing focal segmental glomerulosclerosis, this is almost exclusively seen in black patients 
Management
  • Multidisciplinary team approach aiming for holistic care, suppression of viral load, restoration of CD4 count and treatment adherence with minimal side effects
  • Investigations at the outset:
    • HLA B5701 testing especially if about to commence abacavir
    • HIV antibody testing (if prior documentation is not available or if HIV RNA is below the assay’s limit of detection) 
    • CD4 T-cell count (CD4 count) 
    • Plasma HIV RNA (viral load)
      •  A patient’s pre-ART viral load level and the magnitude of viral load decline after initiation of ART provide prognostic information about the probability of disease progression.
      • High baseline viral loads can influence the choice of treatment, as some HAART treatments are not very effective if a patient has high viral loads
      • isolated blips after undetectable viral levels are not uncommon in successfully treated patients and are not predictive of virologic failure
    • Complete blood count, chemistry profile, transaminase levels, blood urea nitrogen (BUN), and creatinine, urinalysis, and serologies for hepatitis A, B, and C viruses 
    • Fasting blood glucose and serum lipids 
    • Genotypic resistance testing at entry into care, regardless of whether ART will be initiated immediately 
    • HbA1C
    • Note that HIV can also deplete memory B cells and some laboratories may measure memory B cell numbers
  • Initiation of HAART
    • Evidence from START trial that initiation should occur at start of diagnosis (decreases primary end point of serious AIDS illness, serious non–AIDS-related event, or death from any cause)
    • Viral load reduction to below limits of assay detection in an ART-naive patient usually occurs within the first 12–24 weeks of therapy.
    • Regimens should be tailored for the individual patient to enhance adherence and thus improve long-term treatment success.
    •  6% to 16% prevalence of HIV drug resistance in ART-naive patients - therefore should do a pretreatment viral genotype
    • Combination treatments exist, generally combining 2 nucleoside reverse transcriptase inhibitors with a non-nucleoside reverse transcriptase inhibitor or protease inhibitor
    • Patients with cardiovascular disease should avoid protease inhibitor combination and abacavir 
    • Protease inhibitors cause significant lipodystrophy
    • Tenofovir can cause a tubulopathy
    • Significant drug interactions exist
    • new integrase inhibitors are better on side effect profile and may be safer in patients who have cardiac disease
    • In general, 3 agents should be started, two of which should be nucleoside reverse transcriptase inhibitors and one being from another agent (integrase inhibitor, protease inhibitor with ritonavir pharmacokinetic boosting or non nucleoside inhibitor)
    • S/E to consider in choosing optimal therapy:
      • if CKD/ osteoporosis avoid tenofovir as it is associated with a tubulopathy (increased phosphaturia, risk of osteomalacia)
      • avoid efavirenz if there is HIV associated dementia or neuropsychiatric co-morbidities
      • efavirenz increases clearance of methadone, therefore may precipitate withdrawal symptoms 
  • Adherence issues
    • In patients with higher CD4 counts who are at risk of poor adherence, it may be prudent to defer treatment while addressing the barriers to adherence.
    • Pill counting, obtaining pharmacy prescription data
  • Initiation of PRIMARY prophylaxis at
    • CD4 cells < 200 for PCP and CNS toxoplasmosis - Cotrimoxazole DS 1 daily
    • CD4 cells < 50 – azithromycin 1g weekly
  • Secondary prophylaxis continued after induction treatment for OI, until immune restoration on HAART
  • Up to date vaccines
    • Hepatitis A, B
    • Influenzae and pneumococcal vaccine (S. pneumoniae 150 x more common in HIV affected patients)
  • Minimising cardiometabolic risk factors
    • aggressively treating co-morbidities
  • Osteoporosis screening if older than 50
  • Differential diagnosis for neurological disease in context of patient with HIV
    • Work-up: CSF – toxoplasma, EBV, HSV, VZV, JC virus PCR, HIV PCR
    • Consider HIV encephalopathy (HIV viral load in CSF), MRI and neurocognitive assessment
    • Differential diagnosis
      • CNS lymphoma (EBV in CSF), mycobacterial infection (TB), fungal infection (Cryptococcus), bacterial abscess, PML (JC virus PCR)
  • Immune restoration disease (IRD)
    • Most commonly seen with MTB, MAC, CMV but described in nearly all OIs
    • If MTB and CD4 > 50, treat TB and initiate HAART after 4 weeks
    • If MTB and CD4 < 50, treat TB and initiate HAART after 2 weeks