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O. HIV Wasting Syndrome [1] navigator

  1. Advanced HIV Infection only (much reduced with antiretroviral therapy, ART)
  2. Characteristics
    1. Involuntary weight loss >10% of baseline
    2. Absence of alternative diagnosis to explain symptoms
    3. Loss of lean body mass out of proportion to weight loss
    4. Rule out atypical mycobacteria, lymphoma, tuberculosis, other causes of weight loss
  3. Contributing Factors
    1. Chronic infections cause catabolism and wasting (likely due to cytokines such as TNFa)
    2. Malabsorption due to GI dysfunction, chronic infections, others
  4. Overview of Treatments [3]
    1. Exercise and resistance weight training can be very effective
    2. Combining exercise with other modalities may be most effective
    3. Enteral / Parenteral nutrition may be required
    4. Glutamine and/or ß-hydroxy-ß-methylbutyrate
    5. Megesterol Acetate (FDA approved)
    6. Dronabinol (FDA approved)
    7. Testosterone and other Androgens - mainly in men with reduced testosterone levels (also effective in eugonadal men [78])
    8. Anabolic Steroids - oxandrolone (oral), nandrolone (intramuscular)
    9. Human growth hormone (FDA approved)
    10. Exercise training - resistance and aerobic exercise k Thalidomide - inhibits TNFa production, increased weight >3% in most cases [70]
    11. Pentoxifylline (no efficacy to date)
  5. Megesterol Acetate [5]
    1. 400-800mg/d well tolerated
    2. Significant weight gains (without weight loss) in patients with AIDS wasting / cachexia
    3. Can cause adrenal insufficiency and hyperglycemia over long term with high dose
    4. High doses of Provera can also stimulate appetite
    5. FDA approved for HIV wasting
  6. Androgens [7]
    1. About 50% of all men with AIDS are hypogonadal
    2. Serum testosterone levels correlate with lean body mass in men with AIDS
    3. Testosterone enanthate 300mg im given every 3 weeks for 6 months
    4. All subjects had free testosterone levels less than 42 pmol/L (normal 42-121 pmol/L)
    5. Treated subjects gained 2.0kg fat free mass versus loss of 0.6kg for placebo
    6. Patients receiving testosterone reported improved quality of life, energy, appearance
    7. Addition of oxandrolone, an anabolic androgen, to resistance exercise and physiologic testosterone replacement substantially increased lean tissue mass
    8. Alternatively use 200mg testosterone enanthate 200mg im each week [78]
    9. Testosterone injections should be combined with exercise [7,78]
    10. Resistance training exercise is as effective as testosterone injections with better effects on lipid variables [78]
    11. Androstenedione supplements can increase testosterone levels in men [8]
    12. Therefore, superphysiologic androgens may be beneficial in HIV associated weight loss who have reduced testosterone levels
  7. Recombinant Human Growth Hormone (rhGH) [9,10]
    1. rhGH alone or in combination with IGF-1 showed modest improvement in weight gain
    2. There was little change in quality of life or daily activities with rhGH
    3. rhGH may be used in selected patients but is very expensive without clear outcomes
    4. FDA approved for HIV wasting
  8. Dronabinol (THC)
    1. Tetrahydrocannabinol (THC, found in marijuana)
    2. Stimulates appetite in HIV [84]
    3. Dose is 5mg po qd
    4. FDA approved for HIV wasting

P. Central Nervous System (CNS) Disease [11] navigator

  1. Acute / Chronic Encephalitis
  2. Aseptic Meningitis
    1. Herpes Simplex Virus (HSV), Cytomegalovirus (CMV) (CD4<50 cells/µL)
    2. Neurosyphilis
    3. Human Herpesvirus 6 (HHV-6) may be involved in meningitis, dementia of HIV [12]
  3. Seizures
    1. CT scan must be done unless problem is chronic
    2. If chronic problem, new focal deficits and other symptoms must be elicited
    3. Negative CT scan should usually be followed by an spinal tap to rule out infection
  4. Late Problems
    1. Infections: cryptococcus, Progressive Multifocal Leukoencephalopathy (PML) [18]
    2. CNS Lymphoma
    3. Vacuolar Myelopathy
    4. AIDS Dementia - may involve HHV-6 as well as HIV [12]
  5. CNS Lymphoma [13]
    1. Lymphoma limited to cranium and/or spine; CD4 <100/µL most patients
    2. B Cell lymphomas in nearly all cases, many associated with EBV infection
    3. Symptoms: asymptomatic, headache, chang in mentation, visual changes, seizures
    4. Symptoms of increased intracranial pressure: headache, nausea, vomiting, obtundation
    5. Detection by CT (~50% are ring enhancing) or MRI scan
    6. Radiation + Dexamethasone fairly effective
    7. Average Survival: Untreated <1 month, treated ~3 months
  6. Ophthalmological [5]
    1. Ocular involvement in ~60% of adults with AIDS
    2. Most common ocular manifestation is cotton wool spots
    3. CMV Retinitis - retinovitreous disease, up to 40% of patients, CD4 usually <50/µL
    4. Candida and Toxoplasma - no increase in ocular disease in HIV versus normal population
    5. Eyelid disease - Kaposi Sarcoma, Herpes Zoster, molluscum contageousum
    6. Conjunctivitis - nonspecific, possibly autoimmune; up to 10% of HIV+ persons
    7. Rifabutin and Didanosine uveitis
  7. Depression
    1. Very common
    2. Aggressive therapy probably prolongs life; definitely improves quality
    3. Pentoxyphylline 400mg po tid (blocks TNFa production) may have some benefit
  8. Evaluation of Patients with CNS Abnormalities / Symptoms and HIV Infection
    1. MRI or CT: focal enhancing vs. nonenhancing; normal or atrophy
    2. Normal or atrophy found: meningitis, syphilis, dementia
    3. Focal nonenhancing white matter lesions: PML, dementia (consider biopsy; see below)
    4. Focal enhancing lesions: single versus multiple; toxoplasma serology is critical
    5. Positive toxoplasma titers: anti-toxo therapy and reassess in 2-3 weeks (see below)
    6. Negative toxoplasma titers: stereotactic biopsy (lymphoma, toxo, crypto, TB, others)
    7. Followup scans recommended to assess progression and/or treatment efficacy

Q. Central Nervous System Infection [11] navigator

  1. Focal
    1. Toxoplasmosis
    2. Non-Hodgkin's Lymphoma
    3. Progressive Multifocal Leukodystrophy (PML) - JC Virus
    4. HSV 1 and 2 (Encephalitis)
    5. Varicella zoster virus
    6. TB Abscess
    7. Syphilis
    8. CMV Retinitis
  2. Diffuse
    1. Cryptococcal Meningitis
    2. Tuberculous Meningitis
    3. HSV 1 and 2 Encephalitis
    4. CMV Encephalitis
  3. Cryptococcus neoformans [16]
    1. Fungal pathogen causing meningitis in late stage HIV infection
    2. Amphotericin B (0.7 mg/kg IV daily) is drug of choice
    3. Fluconazole 200mg qd-bid orally is acceptable for consolidation phase of therapy
    4. Maintenance therapy with fluconazole 100mg po qd is more effective than amphotericin
    5. Lifelong suppression required with fluconazole
  4. Syphilis
    1. In HIV, disease has accelerated course and commonly involves CNS
    2. Relapse may occur despite usual therapy
    3. Recommend longer treatment courses for primary and secondary syphilis
    4. Neurosyphilis should be excluded with spinal puncture in all HIV-syphilis patients
  5. Toxoplasmosis
    1. CD4 <200/µL (88% of patients); CD4 <100/µL (70%)
    2. Symptoms: change in mental status, focal findings, headache, confusion
    3. Other symptoms: fever, seizures, focal weakness, poor coordination
    4. Laboratory: WBC <4K/µL in 45% of patients
    5. Negative anti-toxo titers in 10-15% (proven disease)
    6. CSF: opening pressure ~160mm H20; WBC<5K/µL, glucose ~50mg/dL, Protein ~55mg/dL
    7. CT Scan: Ring or Diffuse Enhancement 91%, Normal Scan 3%; Edema 78%
    8. MRI is more sensitive than CT; multiple lesions usually seen on MRI
  6. Toxoplasmosis Treatment [19]
    1. Pyrimethamine (75mg qd) and Sulfadiazine (1-1.5gm po qid) has excellent success
    2. Clindamycin 600mg qid + pyrimethamine 75mg qd equally efficacious
    3. Folinic acid 10mg po qd must be given with pyrimethamine
    4. Lack of response in 10-14 days should prompt evaluation to rule out other etiologies
    5. Prophylaxis (see below) [20]
  7. CMV Retinitis [21]
    1. Most common HIV associated eye infection
    2. Usually occurs with CD4 <50/µL
    3. All patients with CD4 <100-200/µL need semiannual eye examinations
    4. May have substantial retinal damage from CMV before symptoms are noted
    5. Anti-CMV agents can be stopped in patients with stable CMV disease and CD4 counts >150/µL [22]
  8. Progressive Multifocal Leukencephalopathy (PML) [23]
    1. Caused by JC virus, a papovavirus (DNA Virus)
    2. May occur in ~4% of patients with AIDS, usually late stage
    3. Clinical and neuroradiologic abnormalities
    4. Focal nonenhancing white matter lesions most commonly found
    5. Stereotactic brain biopsy is usually required for diagnosis
    6. However, polymerase chain reaction (PCR) on CSF is highly specific for diagnosis
    7. Average survival after detection <4 months
    8. No known treatments

R. Peripheral Nervous System Disease [11] navigator

  1. Mononeuritis Multiplex (CD4>500/µL or <50/µL)
  2. Distal Symmetrical Polyneuropathy
    1. Similar to diabetic sensory neuropathy
    2. EMG shows distal axonopathy
    3. Analgesics, tricyclic agents, anticonvulsants and capsaicin may be effective
  3. Inflammatory Demyelinating Polyneuropathy (CIDP related)
    1. CD4<50/µL or >500/µL
    2. Often associated with LP abnormalities
    3. Responses to glucocorticoids, plasmapheresis, intravenous Ig reported
  4. Non-inflammatory Neuropathy, Sensorimotor Disease (early and late)
  5. Autonomic Nervous System
  6. CMV Polyradiculopathy (Cauda equina syndrome) [24]
    1. Patients with CMV infection in cauda equina region
    2. All symptoms of cauda equina destruction may occur
    3. Includes pain, lower extremity weakness, and incontinence
    4. Treatment: Foscarnet or Ganciclovir or both

S. Dermatologic Manifestations [25]navigator

  1. Drug Rashes
    1. Erythema multiforme
    2. Stevens-Johnson Syndrome
    3. Seborrheic Dermatitis
    4. Oral Hairy Leukoplakia
    5. Usual drug rashes - typically with pruritis, urticaria (hives)
  2. Kaposi Sarcoma
  3. Infections
    1. Herpes Simplex Virus (HSV)
    2. Herpes Zoster Virus (VZV)
    3. Molluscum contagiosum
    4. Syphilis
    5. Bacillary angiomatosis
  4. Psoriatic lesions may flare
  5. Eosinophilic folliculitis

T. Kaposi Sarcoma [26] navigator

  1. Neoplasm of endothelial cells due to infection with human herpesvirus 8
  2. Occurs mainly in homosexuals, both HIV infected and noninfected persons
  3. Also occurs in organ transplanation and other immunosuppressed patients
  4. Treatment depends on size/location of lesions
  5. Multimodality therapy is often required in HIV+ patients

U. Thrombocytopenia navigator

  1. Very common in late HIV
  2. Differential Diagnosis
    1. Idiopathic: autoimmune with anti-platelet antibodies
    2. Bone marrow infiltration with infection (such as mycobacteria) or neoplasm
    3. Direct toxicity of HIV on megakaryocytes and/or precursors
    4. Drug Induced
  3. Poor overall response to usual therapy for low platelets
  4. Treatment
    1. Transfuse only for Platelets <10-20K/µL or with symptoms
    2. Glucocorticoids - prednisone 0.5-1.0mg/kg po is usual therapy
    3. ART often has some effect
    4. IVIg - 1gm/kg iv q3-4 weeks required; RhoGam may also be effective
    5. IFNa (3MU sc 3x/week) recently shown benefit in resistant HIV thrombocytopenia

V. Transmission of HIV [2,27,28] navigator

  1. Risk Factors for Transmission
    1. Sexual transmission (homosexual and heterosexual)
    2. Oral-genital only transmission has been documented as well
    3. HIV is shed from genital herpes simplex lesions in HIV-1 infected men [29]
    4. Needle sharing by intravenous drug abusers (IVDA) is increasing source
    5. Prior to blood screening, Factor VIII concentrates were a major problem (before 1985)
    6. Contact with prostitutes
    7. Large number of sexual partners
    8. Infectious HIV is found in the semen even on triple therapy with very low HIV RNA [30]
    9. Plasma HIV RNA levels are also the best predictor of heterosexual transmissibility [31]
    10. Viral load <1500 copes/mL is associated with very rare transmission rates [31]
    11. HAART reduces semen levels of HIV by 1.65 log units over 6 months [77]
  2. Mother to Fetus or Infant Transmission [6,27,36]
    1. Risk of prematurity or other adverse fetal outcome not affected by HIV infection
    2. Risk of transmission of HIV to fetus is ~20% without ART prophylaxis [38,81]
    3. Most transmission occurs from 36 weeks to labor (50% of cases)
    4. 30% of infections occur intrapartum, ~15% at 14-36 weeks, and ~5% in <14 weeks
    5. Breast feeding contributes another 14-20% of infections [89]
    6. Formula feeding is superior to breast feeding, even with ZDV prophylaxis [89]
  3. Prevention of Maternal-Fetal Transmission [6,27,36,73]
    1. ART should be used during pregnancy to reduce perinatal transmission
    2. Triple therapy including NNRTIs can reduce transmission rates to <1.5% [6,36]
    3. Zidovudine (ZDV), another nucleoside reverse transcriptase inhibitor, plus a protease inhibitor are recommended to prevent transmission with HIV RNA >1000/mL [17]
    4. Nevirapine single dose to mother intrapartum and to neonate within 72 hours leads to
  4. 7% overall transmission rates at 18 months, compared with 25.8% for ZDV [88]
    1. Elective cesarean section reduces transmission >50% versus other delivery modes [35]
    2. Cesarean section at 38 weeks should be considered in women with HIV RNA >1000/mL
    3. Amniocentesis is not recommended as it can increase risk of transmission
    4. Standards for treatment change rapidly: for updates, see http://www.hivatis.org
  5. Treating children with perinatal HIV with double or triple ART reduces risk of death by 30% and 71% respectively [75]
  6. Nonoxynol-9 vaginal gel does not reduce (may increase) risk of HIV transmission [86]
  7. Prophylaxis for Occupational or Sexual Exposure to HIV [2,28]
    1. Clear that ART reduces risk of contraction of HIV
    2. Triple drug therapy should be instituted while monitoring viral load for ~6 months

W. Antiretroviral Prophylaxis [43,44,87] navigator

  1. ART Recommended for Treatment or Prophylaxis After Exposure [87]
    1. Combination therapy is always recommended
    2. Nucleoside reverse transcriptase inhibitors (NRTI): Zidovudine, Didanosine, Lamivudine, Abacavir
    3. Non-nucleoside reverse transcriptase inhibitors (NNRTI): Efavirenz, Nevirapine
    4. Protease Inhibitors (PI): Indinavir, Nelfinavir, Lopinavir-Ritonavir, Atazanavir-Ritonavir
    5. Three drugs are usually given
    6. Zidovudine + lamivudine + indinavir prevented recipient infection in one case report of transfusion of HIV+ infected blood [74]
    7. Immune system recovery after true infection with 3 drug therapy is incomplete, but significant [45,76]
  2. Considerations for use of ART in New HIV Infection [2,46,47]
    1. Consultation with clinician experienced in using ART is essential prior to initiating therapy as any treatment limits future options
    2. Goal is increase in CD4 counts and reduction in Viral Load <500/mL
    3. Resistance testing is essential
    4. NNRTI + NRTI Combination (Zidovudine-Lamivudine or Abacavir-Lamivudine) OR
    5. PI + NRTI Combination
  3. HIV Drug Resistance [47,48,49]
    1. Prolonged use of ART, particularly 2 or fewer, can lead to HIV resistance
    2. Poor and partial patient compliance also contributes to generation of resistance
    3. Multidrug resistant HIV strains may have decreased transmissibility
    4. Diagnostic tests for specific HIV mutations should help guide selection of therapies
    5. Genotyping (mutation detection) found drug resistance mutations in 16% of primary HIV-1 infected persons (phenotypic assay correlated in 85% of cases) [50]
    6. Phenotypic assay found resistance >10 fold in 2% of 140 primary HIV infections [51]
    7. Resistance of 2.5-10 fold was found in 36% of 140 patients (unknown significance)
    8. In addition, moderate resistance did not correlate with genotyping data
    9. Therefore, significant HIV resistance is likely to be low in primary infection
    10. Resistance testing is recommended in ALL treatment failures and in pregnant women [71]
    11. Fusion inhibitors effective in highly resistant HIV [4]

X. Prophylaxis for Opportunistic Infections (OI's) [20,72]navigator

  1. Incidence of and prophylaxis for OI's much reduced since advent of ART [52]
    1. OI's are concerning in persons in first few months of initiation of ART
    2. OI's especially concerning in patients with CD4<50/µL
    3. Persons with CD4<50/µL require close surveillance after initiation of ART
    4. Must distinguish between primary and secondary prophylaxis
    5. Prophylaxis may be discontinued in patients with CD4 >200/µL (100-200/µL) for at least 6 months, even in patients with previous infections [85]
  2. Drug interactions must be considered in all patients, particularly those with HIV [82]
  3. PCP Prophylaxis [20,22]
    1. Primary: TMP/SMX DS or SS 1 po qd or 3X/wk; secondary 1 DS po qd
    2. Dapsone +/- Pyrimethamine - check G6PD Levels prior to beginning dapsone therapy
    3. Dapsone dose is 50mg po bid or 100mg po qd; pyrimethamine 50mg po q week
    4. Leucovorin (folinic acid) should also be given 25mg po q week with pyrimethamine
    5. Atovaquone 1500mg po qd may also be used
    6. Primary PCP prophylaxis initiated for CD4<200-250/µL or esophageal candidiasis
    7. Primary PCP prophylaxis can be stopped in patients on ART with CD>200/µL [53,54,55]
  4. Toxoplasmosis
    1. Recommended in patients with toxoplasma Ab+ (IgG+) and CD4 counts <100/µL or with previous infection
    2. TMP/SMX: Bactrim® 1 DS or SS tablet po qd
    3. Dapsone 100mg / Pyrimethamine 50mg both q week nearly as effective as TMP-SMX
    4. Leucovorin 25mg po q week for any use of pyrimethamine
    5. Twice weekly sulfadiazine + pyrimethamine prophylaxis not as effective as daily [56]
    6. Atovaquone 1500mg po qd also effective
    7. Secondary prophylaxis with pyrimethamine 50mg po qd + leucovorin 10mg po qd AND sulfadiazine 1gm po bid-qid OR clindamycin 300mg po qid
  5. Tuberculosis (TB) Overview
    1. Exposure to TB should prompt tuberculin skin test (TST) with 5 units PPD
    2. Positive TB test in HIV+ is >4mm induration
    3. Chest radiography (CXR) recommended for HIV+ with positive TST
    4. Prophylaxis usually with three drugs for HIV+ without active disease by CXR
    5. For treatment of active infection, usually initiate 4 drug regimen
    6. Additional agents may be used if high risk for drug resistance in active TB infection
    7. Any isolates must be cultured for multi-drug resistance
  6. Tuberculsosis Prophylaxis
    1. Isoniazid (INH) 300mg + pyridoxine 50mg both daily or twice weekly for 9 months OR
    2. Two months of INH + rifampin and pyrazinamide
    3. Rifabutin may be substituted for rifampin
    4. Rifampin should not be given with protease inhibitors or NNRTIs
    5. Rifabutin should not be used with protease inhibitor hard-gel saquinavir or delavirdine
    6. Rifampin + pyrazidamide effective for prevention of TB in HIV+ patients [57]
    7. Equally effective for prevention in HIV+ when dosed daily or twice weekly [58]
    8. Most cost effective and best tolerated regimen for prophylaxis in HIV+ persons [58]
    9. HIV+ patients with one episode of TB should receive INH prophylaxis for 1 year following completion of their initial treatment [80]
  7. Mycobacterium avium-complex (MAC)
    1. Prophylaxis for patients with CD4 < 50/µL
    2. Clarithromycin 500mg bid or azithromycin 600mg bid once weekly are approved
    3. Prophylaxis with azithromycin + rifabutin 300mg po qd more effective than single agent
    4. Rifabutin 300mg po qd is also effective, but less so than macrolides
    5. Clarithromycin (first line) should not be used with rifabutin (second line)
    6. Prophylaxis can be discontinued if CD4+ T counts increase to >100/µL >3-6 months [69,79]
    7. Secondary prophylaxis can be discontinued if CD4+ T cells >100/µL for >6-12 months
  8. Candida albicans [59]
    1. Nystatin solution or Clotrimazole troches
    2. Fluconazole (100mg/d) - well tolerated but leads to resistance and is second line
    3. Fluconazole significantly increased cure and improvement over ketoconazole
    4. Long term continuous prophylaxis with fluconazole is not recommended
    5. Intermittant, low dose fluconazole is as effective with less resistance [60]
    6. Intermittant or continuous fluconazole 200mg/d equally effective when CD4+ <350/µL
    7. In patients who develop resistance, fluconazole 800mg/d usually effective
    8. Fluconazole 200mg/week reduces oral and vaginal but not esophageal candidiasis [61]
    9. Fluconazole also reduces risk of cryptococcosis
    10. Itraconazole may also be used for prophylaxis
  9. Cryptococcosis
    1. Routine testing for asymptomatic patients is not recommended
    2. Prophylaxis for cryptococcus should be used if other infections such as candida warrent
    3. Fluconazole 100-200mg po qd reasonable for patients with CD4<50/µL
    4. Prophylaxis may be discontinued with CD4>100/µL for >3 months (limited data)
  10. Cytomegalovirus
    1. Routine CMV serum antibody testing is recommended
    2. Seropositive persons with CD4 cells <50/µL should be considered for prophylaxis
    3. Oral ganciclovir 1000mg tid is effective prophylaxis against CMV (CD4<50/µL [62,63]
    4. Acyclovir or valacyclovir should not be used for CMV prophylaxis
    5. Regular fundoscopic exam by an ophthalmologist is indicated with CD4 <50/µL
  11. Herpes Simplex Viruses (HSV)
    1. Prophylaxis of initial episode of HSV disease is not recommended
    2. Recurrent disease can be prevented with suppressive doses of acyclovir 200-400mg tid
    3. Famciclovir 500mg po bid reduced HSV-2 shedding and reactivation >80-90% [64]
    4. Intravenous foscarnet or cidofovir can be used to treat resistant HSV infections
  12. Varicella Zoster Virus (VZV)
    1. HIV+ persons without a history of vaccination or chicken pox should avoid exposure
    2. For exposure in naive persons, administer VZV immune globulin within 96 hours
    3. Data are lacking on efficacy of antiviral agents
  13. Bacterial Infections
    1. Pneumococcal vaccine for all patients with CD4>200/µL
    2. Humoral response and pneumococcal vaccine efficacy diminished with CD4<200/µL
    3. Type B H. influenza vaccine only recommeded routinely in children
    4. TMP/SMX (usually for pneumococcus) suppresses bacterial respiratory infections
    5. Clarithromycin or azithromycin (for MAC prophylaxis) also reduce bacterial infections
    6. Fluoroquinolones are useful for prevention of enteric infections in endemic areas
  14. Intravenous immune globulin may be of some benefit in severe AIDS
  15. Vaccinations

Y. HIV Vaccine Development [65,66,67,68]navigator

  1. Obstacles to Developing Vaccine
    1. Very high mutation rate of RNA viruses, particularly env protein
    2. Lack of clear understanding of protective immunity to HIV
    3. Rapid and persistent replication of virus
    4. Reservoires of virus with latency in various cell types
    5. Live-attenuated vaccines might recombine with wild-type viruses and become virulent
    6. Difficulty inducing both antibody and cytotoxic T cell responses
  2. Even an incompletely vaccine that only modifies disease course could be useful [68]
  3. Period of weeks after primary infection is likely useful for vaccination
    1. Burst of viremia with dissemination
    2. Early seeding and destruction of gut associated lymphoid tissue (GALT)
    3. Establishment of HIV reservoir with latent component
  4. Antibody Induction
    1. Neutralizing Abs can be produced with surface (gp120 or gp160) vaccines
    2. Abs have some cross-reactivity to other strains but generally do not completely protect
    3. Vaccines with several gp120 proteins may be needed to cover most strains of HIV
  5. Main focus now is using other antigens and stimulating cytotoxic T cell (CTL) responses
  6. DNA based HIV-1 vaccines can induce CTL responses (nef, rev and tat genes used) [66,68]
  7. Therapeutic immunization with recombinant gp160 had mild effect on disease markers [65]

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