Despite these dramatic improvements, several new complications associated with HIV infection and its treatment have emerged. Some patients with advanced disease who are given anti-retroviral therapy develop a paradoxical clinical deterioration during the period of recovery of the immune system despite increasing CD4+ T-cell counts and decreasing viral load. This disorder, called the immune reconstitution inflammatory syndrome, is not understood but is postulated to be a poorly regulated host response to the high antigenic burden of persistent microbes. Perhaps a more important complication of long-term anti-retroviral therapy pertains to adverse side effects of the drugs. These include lipoatrophy (loss of facial fat), lipoaccumulation (excess fat deposition centrally), elevated lipids, insulin resistance, peripheral neuropathy, and premature cardiovascular, kidney, and liver disease. Finally, non-AIDS morbidity is far more common than classic AIDS-related morbidity in long-term HAART-treated patients. Major causes of morbidity are cancer and accelerated cardiovascular disease. The mechanism for these non-AIDS–related complications is not known, but persistent inflammation and T-cell dysfunction may have a role.
MORPHOLOGYChangesinthetissues(withtheexceptionofthebrain)areneitherspecificnordiagnostic.CommonpathologicfeaturesofAIDSincludeopportunisticinfections,Kaposisarcoma,andB-celllymphomas.Mostoftheselesionsarediscussedelsewhere,becausetheyalsooccurinindividualswhodonothaveHIVinfection.LesionsinthecentralnervoussystemaredescribedinChapter23.
BiopsyspecimensfromenlargedlymphnodesintheearlystagesofHIVinfectionrevealamarkedhyperplasiaofB-cellfollicles,whichoftentakeonunusual,serpiginousshapes.Themantlezonesthatsurroundthefolliclesareattenuated,andthegerminalcentersimpingeoninterfollicularTcellareas.ThishyperplasiaofBcellsisthemorphologicreflectionofthepolyclonalBcellactivationandhypergammaglobulinemiaseeninHIV-infectedindividuals.
Withdiseaseprogression,thefrenzyofBcellproliferationsubsidesandgiveswaytoapatternofseverelymphoidinvolution.Thelymphnodesaredepletedoflymphocytes,andtheorganizednetworkoffolliculardendriticcellsisdisrupted.Thegerminalcentersmayevenbecomehyalinized.Duringthisadvancedstage,viralburdeninthenodesisreduced,inpartbecauseofthedisruptionofthefolliculardendriticcells.These“burnt-out”lymphnodesareatrophicandsmallandmayharbornumerousopportunisticpathogens,oftenwithinmacrophages.Becauseofprofoundimmunosuppression,theinflammatoryresponsetoinfectionsbothinthelymphnodesandatextranodalsitesmaybesparseoratypical.Forexample,mycobacteriaoftenfailtoevokegranulomaformationbecauseCD4+ cellsaredeficient,andthepresenceoftheseandotherinfectiousagentsmaynotbeapparentwithoutspecialstains.Asmightbeexpected,lymphoidinvolutionisnotconfinedtothenodes;inlaterstagesofAIDS,thespleenandthymusalsoareconvertedto“wastelands”thatarevirtuallydevoidoflymphocytes.