Prophylaxis Against Opportunistic Infections in Patients with HIV [JA Kovacs and H Masur NEJM 2000;342:1416]: This is one of the series of periodic reviews of opportunistic infection prophylaxis in HIV by Joseph Kovacs and Henry Masur. The following are highlights of this comprehensive state-of-the-art presentation:

• Changes in OI complications: One major review reported that the frequency of OIs decreased by 55% from 1992 to 1997 [MMWR 1999;48 SS-2:1]. The greatest decline was in CMV retinitis, and the least change was for non-Hodgkin's lymphoma.
• Compliance with guidelines: Guidelines were not followed for PCP prophylaxis in 20% of patients with indications [MMWR 1997;46 RR-12:1]. For MAC prophylaxis the rate of non-compliance was 50% [NEJM 1993;329:898].
• Has the relationship between CD4 cell count and the occurrence of OIs been altered by treatment? No.
• Does the nadir of CD4 cell count influence the risk of OIs? Yes.
  The EuroSIDA study, through observation of approximately 7,300 patients, showed that the frequency of OI was approximately three times greater for those with a CD4 cell count nadir <150/mm³ compared to those with a CD4 cell nadir above this level.
• Pneumococcal vaccine issues: The authors recommend repeat immunization every 3-5 years "because antibody titers wane rapidly in patients with HIV infection" [Scand J Infect Dis 1998;30:597]. Patients immunized when the CD4 cell count was <200/mm³ should "probably be re-immunized if the count increases above 200/mm³."
• PCP: The authors recommend avoidance of "high-intensity exposure" to ubiquitous pathogens such as P. carinii and MAC. For P. carinii, this means patients with PCP should not be hospitalized in a room with another vulnerable patient.
• Varicella-zoster: Patients who are seronegative or have no history of chicken pox or shingles and are exposed to chicken pox or shingles should receive VZIG within 96 hours. This is standard, but the statement goes on to say that preemptive therapy with acyclovir, famciclovir, or valacyclovir after exposure in these patients does not have established efficacy.
• Activity of TMP-SMX versus P. carinii: Despite concern about possible in vitro resistance, the authors state that there is no clinical evidence that TMP-SMX prophylaxis is becoming less effective.
• T. gondii prophylaxis: The authors note that all recommended prophylactic regimens for PCP should be effective for toxoplasmosis with the exception of aerosolized pentamidine.
• TB prophylaxis: The current duration of INH prophylaxis is nine months because the six month regimen is less effective [MMWR 1998;47 RR-20:1].
• Secondary prophylaxis: This is recommended for all severe opportunistic infections including PCP, CMV retinitis, cryptococcal meningitis, toxoplasmosis, histoplasmosis, and coccidioidiomycosis. Less serious opportunistic infections that may be treated at the time of recurrence include candidiasis, herpes simplex, and dermatomal zoster.
• Discontinuing prophylaxis: There is substantial data confirming the safety of discontinuing prophylaxis with immune reconstitution for primary PCP prophylaxis, primary MAC prophylaxis, and secondary CMV retinitis prophylaxis. Their recommendation, commensurate with the CDC/IDSA guidelines, is to discontinue prophylaxis for these conditions and for T. gondii when pathogen-specific criteria for immune reconstitution is achieved.
• Discontinuation of CMV secondary prophylaxis: As with the CDC/IDSA guidelines, the authors endorse cautious discontinuation of long-term maintenance therapy if the CD4 cell count exceeds 100 - 150 mm³ for three - six months, if the lesions are not sight-threatening, if there is adequate vision in the other eye, and the patient can be followed by an ophthalmologist. Evidence supporting discontinuation of CMV prophylaxis is provided in the following table, compiled from five published studies:

  Studies of Discontinuation of Secondary CMV Prophylaxis
  Study	Criteria(/ mm3)	#	CD4 count at D/C (median)	F/U(mo)	No. cases CMV retinitis
  Whitcup SM, et al. [JAMA 1999;282:1633]	> 150	14	317	16.4	0
  Macdonald JC, et al. [JID 1998;177:1182]	Increase	11	183	5.2	0
  Tural C, et al. [JID 1998;177:1080]	> 150	7	NS	9	0
  Vrabec TR, et al. [Ophth 1998;105:1259]	> 100	8	255	11.4	0
  Kirk O, et al. [AIDS 199;13:647]	> 100	5	179	12	0

• Restarting OI prophylaxis: The authors recommend restarting prophylaxis for those who do not have sustained immune reconstitution when the criteria for initiating this prophylaxis is reached. They acknowledge that there are no data to verify this recommendation, and they further acknowledge that patients with HIV viral loads >10,000 - 20,000 c/mL may have prophylaxis started earlier.