The risks resistance clinical problems AIDS

Viral resistance always has to be anticipated whenever there is viral replication in the presence of suboptimal drug levels, and thereby resistant mutants gain a selective advantage over the wild-type virus. As a result, there are concerns that resistances could develop both during the washout phase of medication (increasing viral replication with insufficient plasma levels) and on re-initiation of treatment (continued replication despite sufficient plasma levels).

However, in the case of single treatment interruptions, the probability of this does not appear to be particularly high, as shown in 1999 by the small French COMET Study, one of the first studies on treatment interruption (Neumann 1999). But, there is no certainty as to whether interruptions might not eventually lead to development of resistant isolates, which merely require more time until they are able to dominate the wild-type. Mathematical models show that this risk - at least theoretically - is not low, especially if viral load rises to high levels (Dorman 2000, Bonhoeffer 2000).

The risk of resistance is probably higher for repeated treatment interruptions. In several studies, these have led particularly to NNRTI- or 3TC-resistance (Martinez-Picado 2002, Schweighardt 2002, Ruiz 2005). The risk seems particularly high for strategies involving stopping and starting of HAART at fixed intervals (see below). Table 10.1 describes the example of a patient who was clinically well and who interrupted treatment. It was probably the repeated stopping and starting of HAART that ultimately led to resistance in this case.

The sharp increase in viral load that may often occur can present as a retroviral syndrome. The symptoms are similar to acute HIV infection, with lymphadenopa-thy, fever, asthenia and malaise (Colven 2000, Kilby 2000, Zeller 2001, Ruiz 2004). Thrombocytopenia has also been described during interruptions (Ananworanich 2003). The blood count needs to be monitored, especially in patients with a previous history of thrombocytopenia. Finally, attention should also be paid to patients who are co-infected with hepatitis B virus. If the HBV treatment with 3TC, FTC or tenofovir is interrupted, HBV rebound can result in fulminant and life-threatening hepatitis (Sellier 2004). It is therefore advisable to look after these patients very carefully and monitor the liver enzymes at least every two weeks.

Table 10.1: Example of the development of resistance due to repeated treatment interruptions*

Date HAART/comments

CD4 cells Viral load

Jun 97

AZT+3TC+SQV

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