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central nervous system side effects, indinavir- and atazanavir-associated hyperbili-
rubinemia, antiretroviral drug-associated peripheral neuropathy, lipodystrophy and
hyperlipidemia, NRTI-related pancreatitis, and tenofovir-associated renal proximal
tubulopathy. Thus, pharmacogenetics is expected to play an important role in HIV
treatment in the near future.
Role of Diagnostic Testing in Management of HIV
Role of diagnostic testing in management of patients with HIV infection is as follows:
- Detection of HIV-infected individuals
- Evaluation of newly-diagnosed patients
- Monitoring of therapeutic regimens
- Prognosis of disease progression (CD4 plus viral load)
- Management of drug resistance
- Prevention of adverse reactions to drugs
A number of assays have been developed to detect the presence of HIV-1 infec-
tion and quantify the level of virus in the blood of infected individuals:
- EIA tests for the detection and quantifi cation of HIV-1 p24 antigen.
- Western blot.
- Latex agglutination.
- Radioimmunoprecipitation.
- Immunofl uorescence for the detection of antibodies to HIV-1.
- Viral cultures for the isolation and semiquantifi cation of HIV-1.
ViroSeq HIV-1 Genotyping System (Celera) has been cleared by the FDA and is
CE Marked for use in detecting HIV genomic mutations that confer resistance to
specifi c types of antiretroviral drugs, as an aid in monitoring and treating HIV infec-
tion. ViroSeq can be used for managing therapy changes in HIV-1 infected patients
whose drug regimen has failed and in HIV-1 infected individuals at initial presenta-
tion, before starting treatment. ViroSeq’s high throughput processing provides an
integrated system from sample preparation to the fi nal interpretive resistance report
to aid in treatment decisions. ViroSeq can be used to detect HIV-1 subtype B viral
resistance in samples with a viral load ranging from 2,000 to 750,000 copies/mL
and provides sequence analysis of the entire HIV-1 protease gene from codons 1–99
and two-thirds of the reverse transcriptase gene from codons 1–335.
In 2011 ViiV Healthcare, which was formed by GlaxoSmithKline and Pfi zer in
2009 to focus on HIV medications, started a phase III trial for Celsentri/Selzentry.
Called MODERN (Maraviroc Once daily with Darunavir Enhanced by Ritonavir in
a Novel regimen), the trial compares Celsentri/Selzentry with Truvada (emtric-
itabine/tenofovir), both in combination with darunavir/ritonavir. The 96-week trial
assessed a 2-drug regimen against a 3-drug regimen for treating antiretroviral-naive
patients infected with CCR5-tropic HIV-1. MODERN was the fi rst large-scale trial
11 Personalized Management of Infectious Diseases