Ask the Expert: A New Infection With an Undetectable Viral Load

Question: A 40-year-old woman is referred to you by the prison HIV counselor because she had a recent positive HIV test. She was tested by one of the astute internists at your institution because she developed Bell's Palsy about two months into her incarceration (a condition not uncommonly associated with early HIV infection). She is surprised and dismayed by the diagnosis, since she never used injection drugs and was monogamous during the period prior to her incarceration. She had, in fact, been tested for HIV when she applied for her immigration waiver, and she was HIV seronegative. That test was performed about two months prior to incarceration, about six months ago.

You do your best to reassure her, by explaining how a viral load test and CD4 T-cell count will assist you both with a decision on the course of treatment. You decide to repeat the HIV ELISA and Western Blot, just to be sure that the diagnosis is correct. You then arrange to have her HIV studies drawn, and schedule a follow up appointment.

When her blood work returns, it is your turn to be surprised. She has an undetectable viral load. You recheck her HIV test, and it is indeed positive (all the Western blot bands light up). Her CD4 T-cell count is squarely in the normal range, however, on closer inspection you notice that her CD8 to CD4 ratio has "flipped" (CD8 cells >CD4 cells). You worry that the viral load assay was mislabelled, so you repeat it, along with another CD4 T-cell count. Again, the viral load is undetectable but the CD4 is now slightly lower, at the low end of the normal range. You repeat the test again, and the CD4 returns even lower. She is now five months into her incarceration, and you have evidence of fairly rapid CD4 decline and no detectable viral load. What is going on and what should you do?

Answer: Either the patient is an exception to the rule and a lucky member of the "long-term non-progressor" club, or the patient has ongoing viral load replication not identified by viral load PCR of viral replication. The latter is unfortunately more likely since you have already seen a decline in the CD4 T-cell count in a relatively short period of time. Thus, you must consider the possibility that the viral load assay is not detecting the virus, as it would in a case of non-clade B infection.

What is non-clade B infection? As discussed in the main article in this issue, HIV is a very variable virus. Just as the virus may evolve during the course of an individual infection to become a "swarm" of different but related viruses, it has evolved into different but related subtypes in different regions of the world over the course of the HIV epidemic.

HIV-1 is broken down into three large groups, each believed to have arisen from a distinct transmission event, from three different chimpanzee viruses. The M group is the main group, which has dispersed throughout the world. The other two groups, O (outlier) group and a rarely noted non-O, non-M group are only found in West Africa and Cameroon. The M group of HIV-1 has been further broken down into various subtypes, or clades, designated A through K based on variability in the env and gag regions of the viral genome. The predominant subtype in the United States and Western Europe is HIV-1 subtype (clade) B. A is dominant in Eastern Africa, C is dominant in Southern Africa, and a slightly different set of clade C viruses are dominant in India. In Southeast Asia, B and E are the most prevalent. Intersubtype recombinations, or "chimeras," also known as circulating recombinant forms (CRFs) are spreading in China and other areas of the world where the epidemic is just taking off. In the US and Europe, the epidemiology of non-clade B infections is in flux, and recent reports suggest that non-clade B subtypes are becoming more prevalent.12

On closer questioning, you find out that your patient's sexual partner formerly lived in New York City, where non-clade B viruses have been detected. Since some viral load assays can be insensitive to the presence of circulating virus, you repeat the viral load using a branched chain DNA assay and you are now able to detect a positive viral load (75,000 copies per ml).

Although HIV antibody tests do detect non-clade B viruses, not all viral load assays can detect virus in the presence of non-B subtypes (e.g., Roche Amplicor Version 1.0 or reverse transcriptase-polymerase chain reaction [RT-PCR] 1.0). Those that can detect it (branched DNA [b-DNA], Nuclisens, Ultradirect Monitor) may do so but there is a lot of variability between the tests.3 Now that you have found a test that is able to detect the patient's virus, you need to stick with that assay to follow the course of infection. You can also send her virus to be identified at the state Department of Health laboratories.

Since she has acute HIV infection, she should probably be treated with the goals of suppressing the initial burst of viral replication and decreasing the magnitude of virus dissemination throughout the body. This will potentially alter the initial viral set point which may ultimately affect the rate of disease progression, possibly reducing the rate of viral mutation, and preserving immune function.4 You consult an expert in your community about whether it would be appropriate to initiate treatment and with which medication. Your colleague tells you that there may be some variability in the response to treatment by clade or subtype, but that type of information is simply not available because large numbers of individuals with non-clade B subtypes have yet to be studied in detail. Thus there is no reason to modify her regimen by subtype. Early information from treatment of non-clade B infections in Africa suggest that treatment responses are similar to those seen with clade B strains.

The duration of treatment for acute HIV infection is currently not known, however, if her VL becomes undetectable after about 6 months, it may be acceptable to stop treatment. You would of course consult with your colleague, since you are not able to enroll her in a study of STI (see main article).


  1. de Oliveira C.F., Diaz R.S., Machado D.M., et al. Surveillance of HIV-1 genetic subtypes and diversity in the US blood supply. Transfusion. 2000;40:1399-1406.

  2. Barin F., Pillonel J., Buzelay L., Courouce A.M. Increasing diversity of HIV-1 serotypes in French blood donors (1985-1996). In Program and abstracts of the 12th World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 13204.

  3. Holguin A., de Mendoza C., Soriano V. Comparison of three different commercial methods for measuring plasma viraemia in patients infected with non-B HIV-1 subtypes. Eur J Clin Microbiol Infect Dis. 1999;18:256-259.

  4. HHS HIV Treatment guidelines, available on the Web at Additional information from Ball S.C. "HIV-1 Non-B Subtypes in Clinical Practice." 2001 The AIDS Reader 11 (8): 339-400.

Back to the HEPP News October 2001 contents page.