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WHO: AIDS Epidemic Update 2002 - Visit this site

• 42 million people with HIV/AIDS worldwide
• 38.6 million are adults, 19.2 million women and 3.2 million are children under the age of 15
• 5 million new infection with HIV occurred in 2002 of which 4.2 million were adults and 2 million were women
• 3.1 million people died of HIV/AIDS related causes in 2002

Diagnosis

Made by detection of antibodies against the viral antigens by serologic testing.

• First test is ELISA (enzyme linked immunosorbent assay)
  • Sensitivity: higher than 99 percent
  • Specificity: 95 to 99 percent
• A positive ELISA should be confirmed by a second test. Most commonly used is Western blot. Can also use immunofluoresence assays
• Window period exists prior to the development of HIV antibodies. The window period is estimated to be 6 months or less. Patient can be infected but antibody negative in this period.

Treatment

Antiretroviral Regimens

• Non nucleoside Reverse Transcriptase Inhibitor-based Regimens (NNRTI)
  • Three NNRTIs currently marketed for use:
    • Delavirdine
      • The least potent of these agents and is generally not recommended for use as part of an initial antiretroviral regimen
    • Efavirenz
    • Nevirapine
    • Both efavirenz-based and nevirapine-based regimens were compared with PI-based and triple NRTI regimens, as well as to each other
  • The US Department of Health & Human Services (DHHS) panel recommends the following:
    • Efavirenz + (zidovudine or tenofovir or stavudine) + lamivudine as preferred initial NNRTI-based regimens (except for pregnant women). (AI)
    • (Efavirenz + didanosine + lamivudine) (except for pregnant women) or nevirapine-based regimen can be used as an alternative. (BII)
• Protease Inhibitor-based Regimen (PIs)
  • Seven protease inhibitors currently marketed for use:
    • Atazanavir
    • Indinavir
    • Ritonavir
    • Nelfinavir
    • Saquinavir
    • Lopinavir
    • PIs in combination with NRTIs have been evaluated several controlled trials with clinical outcomes
  • The US Department of Health & Human Services (DHHS) panel recommends the following:
    • Lopinavir/ritonavir + (zidovudine or stavudine) + lamivudine as preferred PI-based regimens (AI)
• Triple NRTI Regimen
  • Another approach to antiretroviral therapy is to use triple (3)-NRTI combination
  • Potential advantages the 3-NRTI strategy:
    • Save PIs and NNRTIs for later use
    • Avoid certain PI- or NNRTI-associated adverse effects
    • Minimal drug-drug interactions
    • Some clinicians, however, have concerns over the potency of this single-class regimen as well the potential of development of more NRTI mutations and limitation of future treatment options
  • The US Department of Health & Human Services (DHHS) panel recommends the following:
    • A 3-NRTI regimen consisting of abacavir + (zidovudine or stavudine) lamivudine may be used as an alternative to an NNRTI-based or a PI-based regimen in antiretroviral-naïve patients (CII)
    • This regimen should not be initiated in patients with baseline viral load >100,000 copies/mL (DII)
• Selection of Two Nucleosides as Part of Combination Therapy
  • Eight nucleoside/nucleotide HIV-1 reverse transcriptase inhibitors (NRTIs) are currently marketed:
    • Emtricitabine
    • Zidovudine
    • Lamivudine
    • Tenofovir
    • Didanosine
    • Stavudine
    • Abacavir
    • Zalcitabine - is less convenient and more toxic and should rarely if ever be recommended
  • The US Department of Health & Human Services (DHHS) panel recommends the following:
    • A combination of lamivudine with zidovudine as the 2-NRTI combination of choice as part of a combination regimen (AI). Combination of lamivudine with stavudine (AII) or tenofovir (AII) may be used as alternative.
    • The above is recognized by the panel as a convenient and reasonably potent co-formulation with an acceptable toxicity profile and extensive clinical experience
  • Dual nucleoside combinations are by far the most commonly utilized "backbone" of combination antiretroviral regimens upon which additional third or fourth agents confer sufficient potency for long-term efficacy
  • The choice of the specific two nucleosides is made on the basis of potency, short-and long-term toxicities, drug-drug interactions, the propensity to select for resistance mutations, and dosing convenience

Urologic Manifestations of AIDS

• Renal disease. AIDS associated nephropathy (HIVAN).
• Renal obstruction can result from non-Hodgkins lymphoma causing retroperitoneal lymphadenopathy.
  • Treatment: Systemic therapy (chemotherapy) with use of percutaneous nephrostomy tubes or stents as needed in bilateral disease
• Malignancies
  • Kaposi's sarcoma (KS).
    • Development of KS in HIV population is from a KSassociated herpes virus that is sexually transmitted.
    • Treatment:
      • Small local solitary lesion: local excision, laser fulguration, or radiation therapy
      • Large multi-centric lesions: use radiation therapy for palliation, side effects include urethral strictures and fistulae
      • Disseminated KS: chemotherapy including vincristine, bleomycin, and doxorubicin. Response rates of up to 88 percent are reported. In patients with CD4 count above 600/uL, IFN-a can be used and results in 18to 30-month response.
  • Testicular tumors
    • Most series report an increase in nonseminomatous germ cell tumors but one reported an increase in seminomas
    • Testicular lymphoma in HIV + patients presents in younger men and with higher grade tumor than in non-HIV men. Still overall greater number of germ cell tumors in HIV+ men than testicular lymphomas
  • Urethra
    • Primary urethral T- and B-cell lymphomas reported
• Opportunistic infections
  • Unusual infections found in association with immunosuppression, such as toxoplasmosis, aspergillosis, histoplasmosis CMV, MAI, fungal infections, throughout GU tract including testes and kidneys. Specific infections include the following.
    • Bacterial prostatitis
      • Treat with minimum of 6 weeks of fluorquinolones; relapses are frequent and require retreatment. Prostatic abscess can develop; abscess must be drained transurethrally or transperineally. Can have abscess despite sterile cultures.
    • Fungal prostatitis
    • Diagnosis on fungal stains or cultures of prostatic tissue
    • Treatment is with IV amphotericin (total dose 2 g) plus oral flucytosine. Persistent infection or relapses treated with oral fluconazole
    • Urethra.
      • There is an unexplained association between AIDS and Reiter's syndrome: urethritis, arthritis, and uveitis · Presents as urethral discharge unresponsive to antibiotic therapy
    • Epididymis
      • Can develop salmonella infection, which is difficult to eradicate
      • Treatment is 10 days of IV bactrim followed by life-long oral maintenance therapy.
      • Cytomegalovirus (CMV) epididymitis.
        • Diagnostic histologic appearance for CMV is an inclusion body in the nucleus of the infected cell.
        • Urine culture is positive for CMV
        • Treatment is gancyclovir or likely epididymectomy.
    • Higher incidence of tuberculosis infection in HIV+ men.
• AIDS and semen
  • Viral excretion in the semen is independent of clinical stage of the HIV infection; it does correlate with CD8 counts.
• Impotence
  • Increased incidence of erectile dysfunction from primary and secondary gonadal failure with testicular atrophy and decreased testosterone levels, psychological depression, AIDS-related dementia, and neurogenic dysfunction including peripheral neuropathy from viral myelitis and myelopathy, which occurs in 30 to 40 percent of AIDS patients
• Voiding dysfunction
  • From neurogenic dysfunction as above
  • Associated with high incidence of toxoplasmosis opportunistic infection of CNS
• Fluid and electrolytes
  • Increased incidence of hyponatremia
  • Euvolemic hyponatremia from syndrome of inappropriate antidiuretic hormone (SIADH) secondary to pulmonary or CNS infection
  • Hypervolemic causes include acute renal failure.
  • Hematuria

References

Sexually Transmitted Diseases
Treatment Guidelines 2002
MMWR
Morbidity and Mortality Weekly Report
Recommendation and Reports
May 10, 2002/Vol. 51/No.RR-6

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