Page 100 - HIV/AIDS Guidelines

Assessment of Immunologic Failure. CD4 count should be confirmed by repeat testing. Concomitant
medications should be reviewed carefully, with a focus on those known to decrease white blood cells or,
specifically, CD4 T-cells (e.g., cancer chemotherapy, interferon, prednisone, ZDV; combination of TDF and
ddI), and consideration should be given to substituting or discontinuing these drugs, if possible. Untreated
coinfections (e.g., HIV-2, HTLV-1, HTLV-2) and serious medical conditions (e.g., malignancy) also should
be considered. In many cases, no obvious cause for immunologic failure can be identified.

Management of Immunologic Failure. No consensus exists on when or how to treat immunologic failure.
Given the risk of clinical events, it is reasonable to focus on patients with CD4 counts <200 cells/mm 3
because patients with higher CD4 counts have a lower risk of clinical events. It is not clear that immunologic
failure in the setting of virologic suppression should prompt a change in the ARV regimen. Because ongoing
immune activation occurs in some patients with suppressed HIV RNA levels, some have suggested adding a
drug to an existing regimen. However, this strategy does not result in clear virologic or immunologic
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benefit. Others suggest changing the regimen to another regimen (e.g., from NNRTI-based to PI-based,
INSTI-based, or CCR5 antagonist-based regimens), but this strategy has not shown clear benefit.

An immune-based therapy, interleukin-2, demonstrated CD4 count increases but no clinical benefit in two
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large randomized studies and therefore is not recommended (AI). Other immune-based therapies (e.g., gene
therapies, growth hormone, cyclosporine, interleukin-7) are under investigation. Currently, immune-based
therapies should not be used unless in the context of a clinical trial (AIII).

References

1. d'Arminio Monforte A, Lepri AC, Rezza G, et al. Insights into the reasons for discontinuation of the first highly active
antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. I.CO.N.A. Study Group. Italian
Cohort of Antiretroviral-Naive Patients. AIDS. 2000;14(5):499-507.
2. Mocroft A, Youle M, Moore A, et al. Reasons for modification and discontinuation of antiretrovirals: results from a
single treatment centre. AIDS. 2001;15(2):185-194.
3. Paredes R, Lalama CM, Ribaudo HJ, et al. Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of
antiretroviral treatment failure. J Infect Dis. 2010;201(5):662-671.
4. Schouten JT, Krambrink A, Ribaudo HJ, et al. Substitution of nevirapine because of efavirenz toxicity in AIDS clinical
trials group A5095. Clin Infect Dis. 2010;50(5):787-791.
5. Waters L, Fisher M, Winston A, et al. A phase IV, double-blind, multicentre, randomized, placebo-controlled, pilot study
to assess the feasibility of switching individuals receiving efavirenz with continuing central nervous system adverse
events to etravirine. AIDS. 2011;25(1):65-71.
6. Kieffer TL, Finucane MM, Nettles RE, et al. Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus
production without evolution in treated adults with undetectable HIV loads. J Infect Dis. 2004;189(8):1452-1465.
7. Shiu C, Cunningham CK, Greenough T, et al. Identification of ongoing human immunodeficiency virus type 1 (HIV-1)
replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable
viral loads on durable suppressive highly active antiretroviral therapy. J Virol. 2009;83(19):9731-9742.

8. Siliciano JD, Kajdas J, Finzi D, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1
in resting CD4+ T cells. Nat Med. 2003;9(6):727-728.

9. Eron JJ, Cooper DA, Steigbigel RT, et al. Sustained antiretroviral effect of raltegravir at week 156 in the BENCHMRK
studies, and exploratory analysis of late outcomes based on early virologic responses. Paper presented at: 17th
Conference on Retroviruses and Opportunistic Infections; February 16-19, 2010; San Francisco, CA. Abstract 515.
10. Taiwo B, Gallien S, Aga S, et al. HIV drug resistance evolution during persistent near-target viral suppression. Antiviral
Therapy 2010;15:A38.

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