(+)sense RNA (plus-sense RNA): A virus with a single-stranded RNA genome of the same polarity ('sense') as mRNA.

(-)sense RNA (minus-sense RNA): A virus with a single-stranded RNA genome of the opposite polarity ('sense') as mRNA.

Abortive Infection: When a virus infects a cell (or host), but cannot complete the full replication cycle, i.e. a non-productive infection.

Acute Infection: Relatively brief infections, i.e. a few days to a few weeks, following which the virus is usually eliminated completely from the body by the immune system.

'Arboviruses': A large a diverse group of viruses, taxonomically unrelated which are classically transmitted by arthropod vectors, e.g. mosquitoes, ticks, etc.

Assembly: The stage of replication during which all the structural components come together at one site in the cell and the basic structure of the virus particle is formed.

Attachment: The binding of a virus particle to a specific receptor on the surface of a host cell.

Capsid: A protein shell comprising the main structural unit of a virus particle.

Chronic Infection: The converse of acute infections, i.e. prolonged and stubborn. Caused by viruses which are able to persist in the body.

Complement fixation (CF): An assay for detecting the presence of antibodies reactive against a particular antigen, e.g. a virus.

Envelope: A lipid membrane enveloping a virus particle.

Fusion Protein: The protein(s) on the surface of a virus particle responsible for fusion of the virus envelope with cellular membranes.

Gene expression: An important stage of viral replication at which virus genetic information is expressed: one of the major control points in replication.

Genome replication: The stage of viral replication at which the virus genome is copied to form new progeny genomes.

Haemagglutination-inhibition: An assay used for certain types of viruses which are able to agglutinate red blood cells. Haemagglutination-inhibition records blocking of this process by antibodies, and thus, the presence of antibodies against the virus.

Latent Infection: Viruses which are able to down-regulate their gene expression can establish a truly latent state, i.e. with strictly limited gene expression and without ongoing virus replication. Latent virus infections typically persist for the entire life of the host.

Matrix Protein: A structural protein of a virus particle which underlies the envelope and links it to the core.

Maturation: The stage of viral replication at which a virus particle becomes infectious.

Molecular epidemiology: The use of nucleotide sequence information to study the diversity and distribution of virus populations.

mRNA: Messenger RNA, translated on ribosomes to produce proteins.

Neutralization: Blocking of virus infection by antibodies; also, an assay which measures this.

Nucleocapsid: The core of a virus particle consisting of the genome plus a complex of proteins.

Penetration: The stage of viral replication at which the virus genome enters the cell.

Persistent Infection: Infections in which ongoing virus replication occurs, but the virus adjusts its replication and pathogenicity so as to avoid killing host. They differ from chronic infections in that whereas in chronic infections, the virus is usually eventually cleared by the host (unless the infection proves fatal), in persistent infections, the virus may continue to be present and to replicate in the host for its entire lifetime.

Polyprotein: A long polypeptide encoding several mature proteins which are subsequently released by protease cleavage.

Receptor: A specific molecule on the surface of a cell which is used by a virus for attachment.

Release: The stage of viral replication at which virus particles escape the infected cell.

Tropism: The ability of a virus to infect specific cell or tissue types.

Uncoating: The stage of viral replication at which structural proteins are lost and the virus genome is exposed to the replication machinery.

Vector: An organism responsible for transmitting a pathogen from one host to another, e.g. a mosquito. (In molecular biology, a molecule used to clone nucleic acid sequences).

Virions: Structurally mature, extracellular virus particles.

Virus attachment protein: The protein on the surface of a virus particle responsible for binding the receptor.

Combinations of drugs are at present being used in the West (compare with tuberculosis and leukaemia chemotherapy). Various cocktails, that often have to be individually adapted, are used. As first-line treatment the WHO advises a scheme with 2 nucleoside analogues in combination with an NNRTI ("highly active antiretroviral therapy" or "HAART"). Alternatively, the combination of 2 nucleoside analogues and a protease-inhibitor can be used. Zidovudine, stavudine, lamivudine, abacavir, nevirapine and efavirenz penetrate into the cerebrospinal fluid and can thereby have a preventive effect on the occurrence of AIDS dementia. Any combination treatment should, therefore, contain one of these molecules. Videx® does not penetrate very well into the cerebrospinal fluid.

*

The recommended therapy is a triple therapy consisting of:

• First line: 2 nucleoside analogues + 1 NNRTI

• Second line: 2 nucleoside analogues + 1 boosted protease inhibitor

Initial treatment regimens with minimal patient inconvenience:

• Combivir: 2 x 1 per day, in combination with Kaletra® 2 x 3 per day

  • Or

• Combivir: 2 x 1 per day, with Viramune 2 x 1 per day (for the first two weeks 1 per day)

  • Or

• Trizivir : 2 x 1 per day

  • Or

• Aztec: Once per day, in combination with Videx EC once per day and Sustiva once per day

Combinations of reverse transcriptase inhibitors to be avoided:

• DDC-D4T hence NOT: Hivid + (Zerit, Videx or Epivir), also not Retrovir + Zerit

• DDC-DDI

• DDC-3TC

• AZT-D4T

Combinations of reverse transcriptase inhibitors to be preferred:

• AZT-3TC: Combivir® is a fixed combination of 300 mg AZT with 150 mg 3TC.

• D4T-DDI

• D4T-3TC

• AZT-DDI

• AZT-DDC

Clinicians are aware that the development of resistance is a significant problem in achieving long-term success with highly active antiretroviral therapy (HAART). However, resistance is not an all or none phenomena, but instead comes in gradations. These gradations are defined by the increase in the inhibitory concentration of a particular drug to a level higher than that of wild-type viruses. In some cases viral resistance can be overcome by increasing plasma concentrations, something that is routinely done when ritonavir is used to slow down degradation of protease inhibitors ("boosted PI). The use of the C-trough/IC50 ratio (Inhibitory quotient or “IQ”) has been found to be a useful marker of antiretroviral efficacy.

Note: Compliance

Medication which has to be taken only once daily is easier to take than medication which requires multiple dosing. Once daily regimens improve compliance.

Can be given once daily : Viread®, Emtriva®, Videx EC®, Zerit XR®, Stocrin®, Reyataz®

Metastatic Calcification

• can occur anywhere in the body in tissue which do not normally mineralise when circulating levels of Ca²⁺ and PO₄^3- are increased
• can when tumours of parathyroid gland produce excess parathyroid hormone, or when excessive resorption of bone occurs (eg. tumour in bone)

Dystrophic calcification

• occurs with normal levels of calcium and phosphate in tissues where nuclei allow mineral to precipitate
• such nuclei occurs in degenerating or necrotic tissue
• eg. atherosclerosis, infarcts, tumours, injured tissues

Lithiasis

• occurs within body cavities where degenerating or necrotic cells or micro-organisms provide nuclei for mineral deposition
• eg. urinary tract (uroliathiasis), biliary tract (cholelithiasis) and salivary glands (sialolithiasis)
• stone formation is not only facilitated by but also likely to lead to:
• obstruction of flow
• infection
• inflammation and ulceration