Treatment Update, No. 76. 9(2):1-2); March, 1997
Sean Hosein

This article is based on information presented at the 4th Conference on Retroviruses and Opportunistic Infections in Washington, DC, January 22-26, 1997.

The good news, issues about viral load and questions about the new drugs The news presented at the 4th (American) Conference on Retroviruses and Opportunistic Infections was generally good. For the first time in the history of AIDS, treatments exist which can reduce, and help the immune system partially repair, the damage caused by HIV infection. In some cases, this has extended the lives of people with HIV/AIDS (PHAs). However, researchers have yet to find out which combination of anti-HIV drugs is best, as well as the right order in which to use them.

The good news was balanced however by stories from PHAs and doctors telling of drug toxicity and the growth of HIV that can break through the screen of anti-HIV drugs. There have also been troubling reports of the appearance of the sight-threatening condition CMV retinitis in PHAs who have recently started taking protease inhibitors. Doctors also do not know the long-term effect of these drugs on the immune system. While the results from the use of immune boosters such as interleukin-2 and beta-carotene were disappointing, one research team is busy devising a vaccine that may return some form of immunity back to PHAs. Preliminary results show that the vaccine is safe.

Tests have improved

It is clear that the amount of HIV in the blood, the viral load, has become essential to making decisions about anti-HIV therapies. The goal of many researchers is to drive the viral load in the blood as low as possible -- so low that it cannot be detected. When reading the results of viral load tests it is important to keep at least 4 points in mind.

• First, the technology used for measuring and detecting HIV is constantly being improved. What was considered undetectable a year ago may not be the case today. For instance, the lower limit of detection used to be 500 copies of HIV RNA/ml of blood. Anything below this value was undetectable. That mark quickly fell to 200 copies, and at the conference, one Canadian researcher spoke proudly of the ability to bring it down to 20 copies.
• Second, infections such as the common cold, allergies or a flu shot can stimulate the immune system and temporarily raise viral load. So it is therefore important to keep track of these events and take them into account when interpreting the results of viral load tests.
• Third, although the level of HIV in the blood may be undetectable, this may not be the case in other parts of the body. Only 2% of CD4+ cells are in the blood, the rest are scattered in lymph nodes and tissues throughout the body. Most of HIV is also found in the same locations. Although a powerful combination of indinavir, AZT and 3TC can drive the viral load in the blood down to undetectable levels in some people, production of HIV continues at low levels in the lymph nodes, raising the question: do these drugs really work?
• Fourth, HIV produced in the body can be infectious (called "competent" virus by researchers) as well as noninfectious or 'defective'. The viral load test simply measures the genetic material of the virus -- RNA. It does not measure how infectious the virus is; "copies of both competent and defective virus are detected equally well; thus high viral load does not necessarily reflect [production of large amounts of] competent virus. Viral load measures by themselves do not give a [direct] indication of viral resistance to drugs, nor do they give a direct measure of the state of [a PHAs' immune system]."

Do the new drugs really work?

Potent protease inhibitor combination therapy clearly delays further damage to the immune system, allowing the lymph nodes and bone marrow some relief from overwhelming attack by HIV. No scientist has ever claimed that these drugs will cure HIV infection. Despite treatment, some people continue to fare poorly. Here are several possible explanations for such an outcome:

• poor absorption of drugs
• the drugs are rapidly destroyed by the liver
• other drugs interact with the protease inhibitors, perhaps weakening their antiviral activity or reducing their concentration in the blood
• some drug regimens may simply be too toxic
• people may not take their drugs as directed leading to the development of HIV that is drug-resistant.

A few words of caution

The general consensus among researchers is that PHAs should not stop taking antibiotics to prevent the life-threatening lung condition PCP even if their CD4+ counts rise above 200 cells. Researchers aren?t sure if these increased numbers of cells will protect PHAs from PCP and other infections, such as CMV.

REFERENCES:

1. Connors M, Kovacs JA, Gea-Banacloche JC, et al. HIV induces changes in CD4+ T cell phenotype and repertoire that are not immediately restored by antiviral or immune-based therapies. Oral presentation, abstract 369.

2. Cavert W, Staskus K, Zupancic M, et al. Quantitative in situ hybridization measurement of HIV-1 RNA clearance kinetics from lymphoid tissue cellular compartments during triple-drug therapy. Oral presentation, LB9.

3. Kotler DP, Shimada T and Clayton F. Effect of combination antiretroviral therapy upon mucosal viral RNA burden and apoptosis. Oral presentation, LB11.

4. Schapiro JM, Kamel OW, Winters MA, et al. Lymph node histopathology in HIV-infected patients correlates with duration of response to antiretroviral therapy. Abstract 538.

5. Richmond DD. Resisting resistance: Strategic approaches to preventing and coping with resistance to antiretroviral drugs. Oral presentation S52.

6. Jacobson MA, Kramer F, Pavan PR et al. Failure of highly active antiretroviral therapy (HAART) to prevent CMV retinitis despite marked CD4+ count increase. Abstract 353.

7. Gilquin J, Piketty C, Thomas V, et al. Acute CMV infection in AIDS patients receiving combination therapy including protease inhibitors. Abstract 354.

8. Reinhart TA, Rogan MJ, Viglianti GA, et al. A new approach to investigating the relationship between productive infection and cytopathicity in vivo. Nature Medicine 1997;3(2):218-221.

9. Erbelding EJ and Quin TC. The clinical utility of viral load monitoring in HIV infection: strengths and limitations. Genitourinary Medicine 1996;72:393:395.

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