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nervous system and gastrointestinal tract, remain as reservoirs of infection.[304,305] Though the
turnover of peripheral CD4 cells is rapid, the half-life of FDCs averages two weeks to one
month, while some long-lived CD4 memory cells have a half-life of 7 months, Thus, clearance of
HIV requires months of antiretroviral therapy.[86] Regeneration of the immune system can
occur to some degree even in late stages of HIV infection, but will be slow, variable, and
partial.[81]
Another potential complication of ART that includes tenofovir is accelerated loss of bone
mineral density. The incidence of osteopenia and osteoporosis is increased in HIV infected
males on such therapy. This complication may occur in association with lipodystrophy.[306]
Prophylaxis for Pneumocystis jiroveci (carinii) pneumonia in adults is indicated with
CD4 lymphocyte counts below 200/µL and for patients with a history or oropharyngeal
candidiasis.[208] Prophylaxis for PCP is indicated in infants beginning at 4 to 6 weeks of
life.[307] It may be discontinued when HIV infection is excluded. Otherwise, PCP prophylaxis
is recommended throughout infancy. For children 1 to 5 years of age, prophylaxis is indicated if
the CD4 count is <15% of the total lymphocyte count or if <500/microliter. For children and
adolescents 5 years or more prophylaxis is indicated if the CD4 count is <15% or if
<200/microliter.[282] In patients receiving antiretroviral therapy in whom the CD4 count has
increased above 200/µL for more than 3 months, PCP prophylaxis can be safely
discontinued.[308]
The use of zidovudine and other antiretroviral agents, as well as increased effectiveness
of treatments for opportunistic infections--and the use of prophylactic trimethoprim-
sulfamethoxazole, dapsone, or aerosolized pentamidine (pentamidine isethionate) against
Pneumocystis jiroveci (carinii) pneumonia in particular--has significantly prolonged survival in
persons with AIDS. Access to prompt medical care for ongoing care, prophylactic therapies, and
life-threatening complications of AIDS is also important for survival, as is maintenance of good
nutrition and also psychosocial support.[208,215]
It is clear that use of combination therapies, particularly with inclusion of protease
inhibitors, is quite effective in reducing both the morbidity and the mortality from HIV infection.
The use of prophylactic therapies for prevention of Pneumocystis jiroveci (carinii) pneumonia,
cytomegalovirus, and Mycobacterium avium complex (MAC) infections are most effective in
reducing the prevalence of these infections when aggressive antiretroviral therapy is applied.
The declines in morbidity and mortality occur for all risk groups, ages, races, and sexes.[309]
Minocycline has been investigated as an immunomodulator in HIV infection.
Minocycline modifies T cell activation through decreased cytokine production, altered surface
marker expression, suppression of proliferation, and cell cycle arrest. Minocycline can
potentially diminish IL-2 signaling through decreased CD25 expression and decreased IL-2
production and thereby diminish the reactivation of latent HIV infection. Minocycline
downregulates inflammatory mediators of NF-kB expression, including TNF-alpha and IL-1beta.
This could stabilize and enhance antiretroviral therapy.[310] However, although IL-2 therapy
has been shown to increase the CD4 lymphocyte count in HIV-infected persons, there does not
appear to be a long-term clinical benefit.[311]
There has been considerable pressure to expedite investigational drug testing and
approval, given the uniformly fatal outcome of AIDS. One problem for clinical research trials
has been the propensity of AIDS patients to obtain drugs not on experimental protocols, thus
confounding results of those trials. Patients who are understandably desperate to try anything