- discontinue primary prophylaxis for PCP and MAC in respond ers. Nevertheless, some patients with immune reconstitution have deficits in CTL responses to specific antigens that may result in PCP or relapses in CMV retinitis despite CD4 counts >300 cells/mm3 (JID 2001;183: 1285).
- Idiopathic CD4 Lymphocytopenia (ICL): ICL is a syndrome characterized by a low CD4 cell count that is unexplained by HIV infection or other medical conditions. Case definition criteria include: 1) CD4 less than 300 cells/mm3 or a CD4 percent less than 20% on two or more measurements; 2) lack of laboratory evidence of HIV infection; and 3) absence of alternative explanation for the CD4 cell lymphocytopenia including Sjögren syndrome, sarcoid, radiation, atopic dermatitis, collagen vascular disease, steroid therapy, or lymphoma (NEJM 1993;328:373). Transient, unexplained decreases in CD4 cells may occur in healthy persons (Chest 1994;105:1335; Eur J Med 1993;2:509; Am J Med Sci 1996;312:240). One study of 430 HIV negative TB patients showed 62 (14%) had ICL (JID 2000;41: 167). The CDC receives a report of about one ICL case/month (Dr. T.J. Spira, personal communication). There is speculation that persistent CD4 lymphopenia may be due to diminished stem cell precursors ( Int Arch Allergy Immunol 2005;136:379). Conclusions from the experience with patients having ICL are: 1) they typically lack risk factors for HIV infection; 2) there is no evidence of an infectious etiology based on clustering or contact evaluations; 3) they have fewer OIs than HIV-infected patients for a given CD4 count level; 4) the predominant OIs associated with ICL are cryptococcosis, zoster, molluscum, and histoplasmosis – infections with P. jiroveci, Candida, and HHV-8 (KS) are unusual; 5) their CD4 counts tend to remain stable, and 6) the prognosis is relatively good. In one review of 53 reported cases the median age was 41 years, there was a predominance of cryptococcal meningitis, a median CD4 count of 82/mm3 and only a single case of PCP (Medicine 2007; 86:78). Nevertheless, some have recommended PCP prophylaxis for those with persistent counts <200/mm3, and some have attempted treatment with IL-2 and gamma interferon, but the experience is very limited (Lancet 1992;340:273; NEJM 1993;328:373; NEJM 1993;328:380; NEJM 1993;328:386; NEJM 1993;328:393; Clin Exp Immunol 1999;116:322; CID 2000:3:E20; CID 2001;33:e125; CID 2006;42: e53). Cases of this syndrome should be reported to local/state health departments rather than directly to the CDC as originally advocated.
Resistance Testing
The frequency of ≥1 major resistance mutation in treatment-naïve, recently infected patients, according to studies in North America and Europe from 2000-2007, is 6 -19% (see pg 33).
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