Monitoring Antiviral Therapy:
The goals of antiviral therapy are to enhance immunity and delay or prevent clinical advancement to symptomatic disease without inducing important side effects or selecting for drug resistant virus. Currently, the best marker of a drug’s activity is a decrease in the viral load.
Ideally, before initiating treatment, the viral load and the CD4 cell count should be checked and the viral load test then repeated after approximately four weeks of treatment. If the patient is beginning a regimen that includes two to three drugs for which the patient’s virus does not appear to be resistant, it is expected that the amount of virus should decrease by at least hundredfold during this interval i.e., 4 weeks. The ultimate goal is for the viral load to decrease to undetectable levels which should occur by approximately 24 weeks. Those that are not having an appropriate response to therapy need to be questioned to make sure that they are taking their medications correctly, and if not, why. If the viral load is not going to undetectable levels and the patient is taking the medications correctly, then it is likely that there is a resistant virus to some of the medications. Drug-resistance testing then should be performed and the patient should be managed as described in the next section.
What to do if Viral Load is Increasing while on HIV Therapy:
If the patient suppress their virus to undetectable levels on antiviral therapy but then develops detectable virus, following things should be considered. First, it must be established that the patient is taking the medications correctly. If they are missing doses, then it should be investigated that why this is happening and correct the situation, if possible. If the poor adherence is a result of drug side effects, then one should manage the side effects or consider better tolerated regimen. If poor adherence is occurring because of the medication schedule of dosing, new strategies should be discussed such as placing medications in a pillbox, associating the dosing with certain daily activities such as tooth brushing or possibly changing the regimen. Finally, if the reason for poor adherence is depression, substance abuse, or another personal issue, these issues need to be addressed and managed.
It is important to remember that sometimes, for reasons not entirely understood, the viral load can briefly increase. Unexpected increases, therefore, necessitate repeated testing of the viral load before any clinical decisions are made. If, however, the viral load is continually detected despite proper adherence to the prescribed therapy, serious consideration must be given to the possibility that the virus has become resistant to one or more of the medications being given. There is now plenty of data showing that the use of drug-resistance tests can improve the response to a follow-up regimen. Testing can be used to determine if an individual’s HIV has become resistant to one or more of the drugs that are being taken. There are currently two main types of resistance tests available in the clinic: one that is called a genotype and the other a phenotype assay. The genotype assay looks for mutations in the virus and the phenotype assay assess the actual amount of drug it takes to block infection by the patient’s virus. The genotype test is very helpful in screening for the presence of resistant virus prior to initiating treatment and those experiencing viral rebound on one of their first treatment regimens. The phenotype test is particularly useful in those who are highly treatment-experienced and have substantial amounts of drug resistance. The information derived from these tests, along with a tropism test will ultimately tell the provider which of the many approved drugs are likely to be fully active against the specific patient’s virus. Using this information, the goal is to include at least two and ideally three fully active drugs in the next regimen in order to optimize the chances of suppressing the viral load to undetectable levels.
What to do in case of Missing doses or stopping Antiviral Therapy:
It is strongly advised that individuals on an antiviral regimen not miss any doses of their medications. Unfortunately, life is such that doses often are missed. Reasons for missing doses range from just forgetting to take the medication, leaving town without the medication, or because of a medical emergency, such as the need for urgent surgery. For example, after an appendectomy for acute appendicitis, a patient may not be able to take oral medication for up to several days. When a dose is missed, the patient should contact his or her physician without delay to discuss the course of action. The options in this situation are to take the missed doses immediately or simply resume the drugs with the next scheduled dose.
Although every missed dose increases the chance that the virus will develop resistance to the drugs, a single missed dose should not be cause for alarm. On the contrary, it is an opportunity to learn from the experience and determine why it happened, if it is likely to happen again, and what can be done to minimize missing future doses. Furthermore, if a patient cannot resume medication for a limited time, such as in a medical emergency, there still is no cause for alarm. In this circumstance, the patient should work with their HIV provider to restart therapy as soon as is feasible. Stopping antivirals is associated with some risks of developing drug resistance, and those who wish to stop therapy for any one of a number of reasons should discuss this with their health-care provider in advance to establish the best strategy for safely accomplishing this.
Should patients with the flu- or mono-like illness of primary HIV infection be treated?
There are theoretical reasons why patients identified with HIV around the time they are first infected (primary, acute infection) may benefit from the immediate initiation of potent antiviral therapy. Preliminary evidence suggests that unique aspects of the body’s immune response to the virus may be preserved by this strategy. It is thought that treatment during the primary infection may be an opportunity to help the body’s natural defense system to work against HIV. Thus, patients may gain improved control of their infection while on therapy and perhaps even after therapy is stopped. At one time, the hope was that if therapy was started very early in the course of the infection HIV could be eradicated. Most evidence today however suggests that this is not the case. Consequently, early treatment is not likely to result in a cure, although other benefits may still exist. The current recommendation is that patients with primary infection should be referred to clinical studies where the potential role of therapy can be discussed and further explored. If emotional or social situations make adherence to such treatment questionable, the patients are clearly better off delaying therapy.
What can be done for people who have severe immunosuppression?
Although one goal of antiviral therapy is to prevent the development of immune suppression, some individuals are already immunosuppressed when they first seek medical care. In addition, others may progress to that stage as a result of resistance to antiviral drugs. Every effort must be made to optimize antiviral therapy in these patients. In addition, certain specific antibiotics should be initiated, depending on the number of CD4 cells, to prevent the complications (that is, the opportunistic infections) that are associated with HIV immunosuppression. Guidelines for the prevention of opportunistic infections can be found at http://www.aidsinfo.nih.gov
In summary, patients with a CD4 cell count of less than 200 cells/mm3 should receive preventative treatment against Pneumocystis jiroveci with trimethoprim/sulfamethoxazole (Bactrim, Septra), given once daily or three times weekly. If the patients are intolerant to that drug, they can be treated with an alternative drug such as dapsone or atovaquone (Mepron). Those patients having CD4 cell count of less than 100 cells/mm3 who also have evidence of past infection with Toxoplasma gondii, which is usually determined by the presence of toxoplasma antibodies in the blood, should receive trimethoprim/sulfamethoxazole. Toxoplasmosis is an opportunistic parasitic disease that affects the brain and liver. If a person is using dapsone to prevent Pneumocystis jiroveci, pyrimethamine and leucovorin can be added once a week to dapsone to prevent toxoplasmosis.
Finally, patients with a CD4 cell count of less than 50 cells /mm3 should receive preventive treatment for Mycobacterium avium complex (MAC) infection with weekly azithromycin (Zithromax), or as an alternative, twice daily clarithromycin (Biaxin) or rifabutin (Mycobutin). MAC is an opportunistic bacterium that causes infection throughout the body. Many of these drugs can be stopped if initial antiviral therapy results in good viral suppression and sustained increases in CD4 cells.