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Renal Transplantation in HIV Patients

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Human Immunodeficiency Virus (HIV) has been a major global health problem for longer than three decades now. With the advent of HAART or cART (combined anti retroviral therapy) and effective …

Human Immunodeficiency Virus (HIV) has been a major global health problem for longer than three decades now. With the advent of HAART or cART (combined anti retroviral therapy) and effective prophylaxis against opportunistic infections survival has increased markedly. Hence morbidity from other diseases like end stage liver disease, renal and heart disease is increasing rapidly. Presence of HIV infection used to be regarded as a contraindication for renal transplant for fear of exacerbating an already immunocompromised state further with immunosuppressants, use of limited supply of donor organs in individuals with unknown outcome and also the risk of spread of infection to health care staff. With HIV related kidney disease becoming a relatively common cause of ESRD requiring dialysis and its rapid progression to AIDS and mortality renal transplantation was attempted at various centers across the globe in HIV affected patients with good success rates allaying initial fears.

Our experience in kidney transplantation of HIV patients are enthusiastic with very good patient and graft survival at par with nonHIV patients. HIV infection is now no longer a contraindication to renal transplantation and is being considered standard therapy. This review examines open questions in kidney transplantation in patients infected with HIV and clinical strategies that have resulted in good outcomes. It also discusses the clinical concerns associated with the treatment of renal transplant recipients with HIV.

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  • 1. RenaltransplantationinHIVpatients
  • 2. Review ArticleRenal transplantation in HIV patientsD.K. Agarwal a,*, Aashish Sharma b, Anupam Bahl c, Nalin Nag d, S.N. Mehta eaSenior Consultant, Department of Nephrology, Indraprastha Apollo Hospital, New Delhi, IndiabAssociate Consultant, Department of Nephrology, Indraprastha Apollo Hospital, New Delhi, IndiacRegistrar, Department of Nephrology, Indraprastha Apollo Hospital, New Delhi, IndiadSenior Consultant Internal Medicine, Indraprastha Apollo Hospital, New Delhi, IndiaeSenior Consultant Transplant Surgery, Indraprastha Apollo Hospital, New Delhi, Indiaa r t i c l e i n f oArticle history:Received 4 January 2013Accepted 15 January 2013Available online 24 January 2013Keywords:Human Immunodeficiency Virus(HIV)HAARTCART (Combined Anti RetroviralTherapy)HIV-related nephropathy (HIVAN)a b s t r a c tHuman Immunodeficiency Virus (HIV) has been a major global health problem for longerthan three decades now. With the advent of HAART or cART (combined anti retroviraltherapy) and effective prophylaxis against opportunistic infections survival has increasedmarkedly. Hence morbidity from other diseases like end stage liver disease, renal and heartdisease is increasing rapidly. Presence of HIV infection used to be regarded as a contra-indication for renal transplant for fear of exacerbating an already immunocompromisedstate further with immunosuppressants, use of limited supply of donor organs in in-dividuals with unknown outcome and also the risk of spread of infection to health carestaff. With HIV related kidney disease becoming a relatively common cause of ESRDrequiring dialysis and its rapid progression to AIDS and mortality renal transplantationwas attempted at various centers across the globe in HIV affected patients with goodsuccess rates allaying initial fears.Our experience in kidney transplantation of HIV patients are enthusiastic with verygood patient and graft survival at par with nonHIV patients. HIV infection is now no longera contraindication to renal transplantation and is being considered standard therapy. Thisreview examines open questions in kidney transplantation in patients infected with HIVand clinical strategies that have resulted in good outcomes. It also discusses the clinicalconcerns associated with the treatment of renal transplant recipients with HIV.Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.1. IntroductionWith the introduction of anti retroviral therapy, prognosis ofHIV infection has been improved. While the frequency of AIDSdefining events has decreased as a cause of deathemortalityfrom nonAIDS related events including end stage renal dis-ease has increased.Renal diseases directly related to HIV infection includeHIV-related nephropathy (HIVAN), immune-complex dis-eases and thrombotic microangiopathy. Most aggressiveHIV related renal disease is HIVAN. It is currently the thirdmost common etiology of ESRD among African Americansafter diabetes and hypertension in the 20e64 age group.1Co-infection HBV or HCV is also common. Almost 1%* Corresponding author. B-109, Alpha-1, Greater Noida, Gautam Budh Nagar, U.P. 201310, India. Tel.: þ91 120 2326068, þ91 9811200113(mobile); fax: þ91 120 2320052.E-mail address: dmas100@gmail.com (D.K. Agarwal).Available online at www.sciencedirect.comjournal homepage: www.elsevier.com/locate/apmea p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 60976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apme.2013.01.008
  • 3. patients with ESRD in US and Europe are estimated to haveHIV.Widespread use of cART has reduced the incidence of HIVrelated renal disease though renal disease per se continuesto increase among this population.2Potential explanationsinclude inadequate HAART, drug toxicity, increased survivalrates causing an increase in elderly population and chronicviral co-infections. Nephrotoxic effects could be induced orexacerbated by antiretroviral medications like indinavir,atazanavir, ritonavir or infection prophylaxis drugs like tri-methoprim sulfamethoxazole. Calcineurin inhibitors (CNIs)like cyclosporine and tacrolimus used in immunosuppressivetherapy are nephrotoxic and their effects can be exacerbatedby cytochrome P450 inhibition by HAART agents like proteaseinhibitors (PIs) and medications commonly used for fungalprophylaxis like fluconazole. In addition some HAARTagents can induce diabetes mellitus, hypertension andhyperlipidemia all of which are risk factors for ESRD. Man-agement of coinfection with hepatitis C virus is anotherchallenge. Treatment by a team of specialists is criticallyimportant in HIV infected renal transplant patients.With HAART therapy now survival in CKD Stage V patientson dialysis with high CD4þ T cell counts is similar to thosewithout HIV. Renal transplantation has also been found safeand effective in patients with HIV.In our study of HIV positive patients undergoing renaltransplant we found HIVAN to be the cause of renal failure in33.3% of cases. Other causes were hypertensive nephro-sclerosis (16.6%), analgesic nephropathy (16.6%) and CGN(16.6%) and CIN (16.6%).2. Early outcomes of transplantationThe first prospective study performed demonstrated a similar1 year patient and graft survival rates in patients with andwithout HIV.3However more than half the patients sufferedacute rejection requiring aggressive treatment with anti lym-phocyte globulin. Subsequent studies confirmed that patientand graft survival rates are similar though rejection rates arehigher in HIV infected patients. Roland et al found patient andgraft survival rates 94% and 83% respectively at 3 years, withhigh incidence of acute rejection.4In study of 150 HIV infectedrenal transplant patients by Stock PG et al, patient and graftsurvival was found to be 88.2% and 73.7% respectively at 3years.5Rates of acute rejection of renal transplants in patientswith HIV range from 13% to 67%.6A higher acute rejection rateis seen in patients of sub Saharan African descent.7In our case study of the six HIV infected patients whounderwent renal transplant one suffered acute rejection[Table 1]. Of these four out of six had received induction withIL-2 receptor blocker Basiliximab. Patient and graft survivalwas 83.4% each at 30 months. We found no difference be-tween use of cyclosporine Vs tacrolimus.3. Patient selection criteriaThese criteria keep evolving as our experience in managingthese patients increases. Traditional selection criteria werepredicted by the concern that immunosuppression wouldaccelerate progression of HIV to AIDS. This however did nothappen and the selection criteria gradually became more lib-eral. These selection criteria are based on the North Americanand European transplantation criteria.3.1. Inclusion criteria- Meets standard criteria for inclusion in renal transplant list- CD4þ T cell count >200 at any time in the 4 weeks beforetransplantation- HIV RNA <40 log copies for 4 months prior to transplant- No change in HAART regime for 3 months beforetransplantation- Ability and willingness to comply to the immunosup-pressive regime and HAART therapy- Primary medical care provider having expertise in HIVtreatment- Ability and willingness to undergo prophylaxis for pneu-mocystis pneumonia, herpes virus and fungal infection- If hepatitis C co-infection is present ability and willingnessto undergo frequent post transplant monitoring as man-dated by the medical care provider- If h/o pulmonary coccidiodomycosis exists, patient must bedisease free for at least 5 years before transplantation- If there is h/o neoplasms like cutaneous Kaposi sarcoma,in situ anogenital carcinoma, adequately treated basal orsquamous cell carcinoma of he skin then patient should bedisease free for at least 5 years before transplantation- If h/o renal cell carcinoma then patient should be diseasefree for at least 2 years pretransplant- Ability to provide informed consenteself or by guardian- Female candidates should have negative HCG pregnancytest 14 days pretranplant.3.2. Exclusion criteria- Age < 1 year- Detectable HIV RNA (or more than 40 log copies)- h/o PML, lymphoma, chronic intestinal cryptosporidiosis- h/o MDR fungal infection unlikely to respond to routinelyused antifungals- h/o any neoplasm except those mentioned in the inclusioncriteria- Substance abuse- Any advanced cardiac or pulmonary disease- Anatomic abnormality precluding transplantation surgery- Use of IL2 or GMCSF in 2 months preceding transplantation- Cirrhosis on liver biopsy unless patient is being taken up forcombined liver- kidney transplantTable 1 e Post transplant complications n [ 6.Complications n %ATN 1 16.6CNI toxicity 2 33.3Sepsis 1 16.6Acute rejection 0 16.6Chronic rejection 1 16.6Relapse HIV 0 0a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 6 51
  • 4. Table 2 e Antiretroviral dosing recommendations in patients with renal impairment.Antiretrovirals Renal insufficiency HD/CAPDNucleoside reverse transcriptase inhibitor’s (NRTI’S)Abacavir No dosing adjustment is needed No dosing adjustment is neededHD/CAPD minimally eliminated. Could be dosedindependently of HD session.Didanosine(enteric coated)60 kgCrCl 60:400 mg every 24 hCrCl 30e59:200 mg every 24 hCrCl 30:125 mg every 24 h60 kgCrCl 60:250 mg every 24 hCrCl 10e59:125 mg every 24 hCrCl 10:not suitable for use in patients60 kg with CrCl10 ml/min an alternateformulation of didanosine should be used(videx pediatric powder for oral solution75 mg every 24 h)HD/CAPD; 125 mg every 24 h. It is not necessary toadminister a supplemental dose after HDHD/CAPD; an alternate formulation of didanosine should beused (videx pediatric powder for oral solution 75 mg every24 h)Emtricitabine CapsulesCrCl 50:200 mg every 24 hCrCl 30e49:200 mg every 48 hCrCl 15e29:200 mg every 72 hCrCl 15 :200 mg every 96 hOral solution 10 mg/ml dueto a difference inbioavailability of emtricitabine between thehard capsule and oral solution presentations.240 mg emtricitabine administered as the oralsolution (24 ml) should provide similarplasma levels to those observed afteradministration of one 200 mg emtricitabinehard capsule.CrCl 50:240 mg (24 ml) every 24 hCrCl 30e49:120(12 ml)mg every 24 hCrCl 15e29:80 mg (8 ml)every 24 hCrCl 15:60 mg(6 ml) every 24 hCapsulesHD: 200 mg every 96 h, after HDCAPD:No data availableOral solution (10 mg/ml)HD:60 mg(6 ml) every 24 h after HDCAPD- No data availableLamivudine CrCl 50:150 mg every 12 h or 300 mg every24 hCrCl 30e49:150 mg every 24 hCrCl 15e29:100 mg every 24 h(1st dose 150 mg)CrCl 5e14:50 mg every 24 h(1st dose 150 mg)CrCl 5:25 mg every 24 h(1st dose 50 mg)HD:25 mg every 24 h(1st dose 50 mg),after HDStavudine 60 kgCrCl 50:40 mg every 12 hCrCl 26e49: 20 mg every 12 hCrCl 10e25:20 mg every 24 hCrCl 10:20 mg every 24 h60 kgCrCl 50:30 mg every 12 hCrCl 26e49:15 mg every 12 hCrCl 10e25:15 mg every 24 hCrCl 10:15 mg every 24 hHD:20 mg every 24 h,after HDHD:15 mg every 24 h,after HDZidovudine Significantly elevated GZDV (the majormetabolite of zidovudine)plasmaconcentrationsCrCl 10e50:250e300 mg every 12 hCrCl 10:250e300 mg every 24 h300 mg every 24 h after HDHD and CAPD appeared to have a negligible effect on theremoval of zidovudine, whereas GZDV elimination wasenhancedNucleotide reverse transcriptase inhibitors (NtA’S)TenofovirdisoproxilfumarateCrCl 50: usual doseCrCl 30e49: 300 mg every 48 hCrCl 10e29: 300 mg every 72e96 h (dosingtwice a week)No dosing recommendations can be given fornon-HD patients with creatinineclearance10 ml/minHD: 300 mg tenofovir disoproxil (as fumarate) may beadministered every 7 days following completion of an HDsession (assuming three HD sessions per week, each of 4 hduration or after 12 h cumulative HD)a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 652
  • 5. Table 2 e (continued)Antiretrovirals Renal insufficiency HD/CAPDNon nucleoside reverse transcriptase inhibitors (NNRTI’S)Efavirenz Usual dose HD: limited data suggest that there is no reason to adjust thedoseCAPD: pharmacokinetic data of only one patient suggestthat there is no reason to adjust the dose.Nevirapine CrCl 20 ml/min usual dose HD: an additional 200 mg dose of nevirapine following eachdialysis treatment is recommended.Etravirine(TMC-125)Usual dose HD/CAPD: as etravirine is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDProtease Inhibitors (PI’S)Amprenavir Usual doseBecause of the potential risk of toxicity fromthe large amount of the excipient propyleneglycol, agenerase oral solution iscontraindicated in patients with renal failureHD/CAPD:as amprenavir is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDAtazanavir Usual dose HD/CAPD:as atazanavir is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDHD:consider using atazanavir boosted with ritonavir.Although ATV was negligibly eliminated by HD (2%),subjects on HD had substantially lower ATV levels thancontrols(AUC 42% lower on HD days,28% lower on non HDdays). The mechanism of this effect is not known (limiteddata). Therapeutic drug monitoring is advised.Darunavir Usual dose HD/CAPD:as darunavir is highly bound to plasma proteins, itis unlikely that it will be significantly removed by HD or PDFosamprenavir Usual dose HD/CAPD:as amprenavir is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDIndinavir Usual dose HD: limited data, showed minimal elimination of indinavirduring a dialysis sessionLopinavir Usual dose HD: usual dose. In 13 patients 2 were on HD LPV AUC valueswere similar to those obtained in patients with normal renalfunctionCAPD: No data available as lopinavir and ritonavir are highlybound to plasma proteins, it is unlikely that it will besignificantly removed by CAPDNelfinavir Usual dose HD:it is unlikely that it will be significantly removed by HD.Data from one patient showed no removal of nalfinavir bya 4 h HD session.CAPD: it is unlikely that it wll be significantly removed byPD.Data from one patient showed dialysate nalfinavirconcentration below the limit of detectionRitonavir Usual dose HD/CAPD:as ritonavir is highly bound to plasma proteins, itis unlikely that it will be significantly removed by HD or PDSaquinavir Usual dose HD/CAPD:as saquinavir is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDTipranavir Usual dose HD/CAPD:as tipranavir is highly bound to plasma proteins,it is unlikely that it will be significantly removed by HD or PDFusion inhibitorsEnfuvirtide (T-20) No dose adjustment is needed HD: usual dose (limited data)CCR5 Co receptor antagonistMaraviroc (UK-427857) No dose adjustment is needed without potentCYP-3A4 inhibitors or inducers. Posturalhypotension may increase the risk ofCardiovascular adverse events in patientsreceiving maraviroc who have severe renalimpairment or ESRD (CrCl 30 ml/min).maraviroc should not be prescribed forpatients with severe renal impairment whoare receiving CYP-3A4 inhibitor or inducer.HD/CAPD:No data availableIntegrase inhibitorsRaltegravir (MK-0518) No dose adjustment is needed No data availablea p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 6 53
  • 6. - Substantial wasting or malnutrition- Concomitant condition which inthejudgment ofmedicalcareprovide precludes transplantation or immunosuppression.Approximately 30% patients with HIV have hepatitis Cco-infection and 10% hepatitis B co-infection. In patientswith either co-infection extent of liver damage needs to beassessed before kidney transplantation. Data suggests thattreatment with HAART or MMF might help in slowing pro-gression of liver disease and improve survival rates aftertransplantation.4. Donor selection criteriaUnited Network for Organ Sharing (UNOS) database hasdemonstrated reduced death-censored graft survival at 1 yearin patients with HIV and renal transplants from deceaseddonors older than 50 years of age and cold ischaemia timelonger than 16 h.8Strategy to combat these problems is to useliving donors or infectious high risk donors i.e. individualswho tested negative for HIV, HBV and HCV but based on socialhistory could have become infectious shortly before becomingkidney donors. Use of extended criteria deceased donors isappropriate for elderly HIV positive patients. Use of pediatricen-bloc kidneys is not recommended because of high risk ofrejection and the possibility that these small kidneys mightnot tolerate this rejection.5. Strategies for immunosuppressionAgents used as immunosuppressives have antiretroviralproperties. MMF has virostatic action by depletion of guano-side nucleosides required for virus replication. Cyclosporineand tacrolimus interfere with HIV pathogenic protein. Siroli-mus causes suppression of T cell activation and antigen pre-senting cell function and disruption of virion replication andentry into monocytes and lymphocytes by decreasingexpression of chemokine receptor.Renal transplant recipients with HIV have a higher rejec-tion rate hence induction therapy with IL2 receptor blockerhas been introduced.9Most transplant centers are reluctant touse lymphocyte depleting agents as they can severely depleteCD4þ T cells for several months, though they have reversedaggressive rejections successfully. In our patients four out ofsix patients received IL2 receptor blocker Basiliximab withoutany side effects (Table 1).6. Drug interactionsManagement of HIV patients post transplant is complicated bymultiple drug interactions between HAART agents and im-munosuppressants. Most notable among these is induction orinhibition of cytochrome P450 3A and P-glycoprotein 1 fluxtransporters. These interactions can lead to unexpected in-creases or decreases in drug levels leading to toxic side effects,organ rejection and HIV disease breakthrough. PIs inhibitP-glycoprotein and CYP 3A activity. This results in increasedlevel of circulating drugs. Non nucleoside reverse tran-scriptase inhibitors (NNRTIs) like efavirenz reduce CYP 3Aactivity increasing drug metabolism and reducing plasmadrug levels.Patients on PIs and cyclosporine required only 20% of theimmunosuppressant dose administered to renal transplantrecipients without HIV as per a study describing the phar-macokinetics and dosing modifications of cyclosporine, siro-limus and tacrolimus in liver or kidney transplant recipientson NNRTIs, PIs or both.10Low dose ritonavir a potent inhibitorof P glycoprotein 1 and CYP 3A4, is often used to boost plasmalevels of other PIs. Patients on a ritonavir boosted PI regimenrequired even lower doses of immunosuppressants than pa-tients on other HAART regimens. In patients on tacrolimus orsirolimus immunosuppressant dose was markedly decreasedand the dosing interval too increased more than five fold. Wefound that patients on one NRTI, one NNRTI and one PIrequired a dose reduction of almost 97.5% instead of around50% as has been routinely quoted. We needed a dose reductionof around 92% in immunosuppressive dosage on a HAARTregime of 2NRTIs and 1PI instead of around 85% as routinelyquoted. On a 2NRTI and 1NNRTI combination an increase by50% in CNI dose was seen in our patients instead of 25% asroutinely used.Other drug interactions include azole antifungals andmacrolide antibiotics also inhibiting CYP3A 4 system. Protonpump inhibitors routinely taken along with corticosteroidsreduce intestinal absorption of PI atazanavir. Therefore pa-tients on proton pump inhibitors and atazanavir require PItreatment to be boosted by use of ritonavir. Zidovudine andMMF combination is not preferred as MMF antagonizes antiretroviral effect of zidovudine and myelotoxic effect of MMFgets enhanced with the additive myelosuppressive effect ofzidivudine11[Tables 2 and 3].7. Management of comorbiditiesHBV- Lamivudine resistance is common in kidney transplantpatients with lamivudine containing HAART regimens.Tenofovir is an acceptable alternative.HCV- Management of HIVeHCV co-infection is problem-atic. Post transplant immunosuppression exacerbates hepa-titis C infection. Clearance of HCV should be attempted pre-transplant as interferon therapy post-transplant leads toincreased graft rejection in a population that is already ata greater threat of rejection. Early data on kidney trans-plantation has shown favourable results of transplantation inpatients with HIV HCV co-infection. Long term studies arehowever required and are currently underway.97.1. Bone metabolism disordersRenal transplant patients with HIV are particularly at riskbecause of renal failure associated hyperparathyroidism, lowvitamin D levels leading to low bone turnover, metabolicacidosis and reduced patient physical activity leading toosteoporosis, steroid intake, HIV associated low androgenlevels in males and females and administration of anti-retrovirals like tenofovir and didanosine which have beena p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 654
  • 7. associate with low bone mass. Bisphosphonates can be triedto restore bone mass levels.7.2. Prophylaxis to prevent comorbiditiesRenal transplant recipient patients with HIV should receivethe standard postetransplantation prophylaxis [Table 4]. Ifpatients receive lymphocyte depleting agents as anti-rejectiontherapy then prophylaxis should be given for 3e6 monthsafter discontinuation of antirejection therapy. For PCP lifelongprophylaxis with TMP-SMX is recommended by most centers.Vaccinations according to HIV guidelines should be given tothese patients.127.3. Cardiovascular diseasesPresence of hypertension, dyslipidemia caused by PIs, CNIscausing vasoconstriction and abnormal vascular remodeling,steroids and CNIs causing diabetes all aggravate car-diovascular risk. Atorvastatin or pravastatin are preferredagents as they have lower propensity to inhibit CYP3A orP-glcoprotein 1. Combination with fibrates increases myotoxiceffects.7.4. CancerSince advent of HAART incidence of Kaposi sarcoma and non-Hodgkin’s lymphoma rates have declined. Hepatocellularcarcinoma rates have increased probably in part related tothe increased longevity of HIV patients with HBV, HCVco-infection. Regular surveillance for HCC is required. Patientsshould be offered all conventional therapies including livertransplantation in case of its occurrence. There is increasedrisk of development of human papilloma virus associatedcervical and anal cancers for which routine Pap smears andcolonoscopies should be performed.8. ConclusionsRenal transplantation is both safe and effective in patientswith HIV associated renal failure.In these patients HIV load remains suppressed, CD4þ T cellcounts stable and opportunistic infections do not seem toincrease considerably.Rates of acute rejection are higher. However graft survivalis at par with nonHIV transplant patients now a days.HIVeHCV coinfection is a major concern in terms oftreatment options and long term effects.It is important to have a team of doctors to overseetreatment comprising HIV and infectious disease specialist,nephrologist, transplant surgeon and primary carephysician.Table 3 e Antiretroviral drug regimens for HIV infectedtransplant patient.1. NRTIs A combination of two NRTIs (for example tenofovir plusemtricitabine or abacavir plus lamivudine) can be used safetyin renal transplant recipients with dose adjusted to renalfunction. Tenofovir should be used with caution and close monitoring ofrenal function. Abacavir should not be used in recipients receiving a kidneyfrom an HLA-B57*01-positve donor to avoid the potential riskof hypersensitivity reaction to abacavir.2. NNRTIs and protease inhibitors Can be used safely in combination with two NRTIs. Important interactions with immunosuppressive drugs mayappear, mainly with protease inhibitors.3. Novel classes of antiretrovirals Must be considered in combination with NRTIs. Integrase inhibitors (raltegravir): have no interactions withimmunosuppressive agents at the CYP450 level. Entry inhibitors (enfuvirtide (T20): could be an alternative incombination with NRTIs, although subcutaneous admin-istration is a limitation. CCRS co-receptor antagonists (Maraviroc): a substrate ofCYP450. Its levels can be modified by inducers or inhibitors.Experimental studies have suggested that maraviroc couldhave an important role as an antirejection drug.Table 4 e Recommended prophylaxis regimens for renal transplantation candidates with HIV.Condition Primary prophylaxis Secondary prophylaxisPneumocystis carinii Indicated for life; TMP-SMX Same as primaryPneumonia Alternative- dapsone or atovaquoneToxoplasmosis when þ ve Toxoplasma IgG or CD4þ T cell200/ml, T/tof Choice- TMP-SMX Discontinue whenCD4þTcell200/ml for 3e6monthsCD4þTcell200sulphadiazine þ pyrimethamine þ leucovorin Discontinuewhen CD4þTcell 200/ml for 3e6monthsMycobacteriumavium complexwhen CD4þTcell50/ml drug- azithromycin/clarithromycin discontinue when CD4þTcell100/mlfor 3e6monthswhen CD4Tcell50/ml drug clarithromycin þ ethambutolCMV no HIV specific indication when CD4þTcell75e100/ml Drug- valganciclovir Orfoscarnet or cidofovir Discontinue when CD4þTcell 200/mlfor 3e6monthsExtrapulmonaryCryptococcusno specific HIV indication when CD4þTcell200/ml drug- fluconazole Discontinuewhen CD4þTcell 200/ml for 3e6 monthsHistoplasmosis no specific HIV indication Indicated for life regardless of CD4þTcell count Drug-itraconazolea p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 6 55
  • 8. Conflicts of interestAll authors have none to declare.AcknowledgementWe acknowledge the contribution of our transplant teamincluding doctors, nurses and health workers.r e f e r e n c e s1. Trullas JC, Barril G, Cofan F, et al. Prevalence and clinicalcharacteristics of HIV type-1 infected patients receivingdialysis in Spain: results of a Spanish survey in 2006: GESIDA48/05 study. AIDS Res Hum Retroviruses. 2008;24:1229e1235.2. Ahuja TS, Borucki M, Funtanilla M, et al. Is the prevalence ofHIV-associated nephropathy deceasing? Am J Nephrol.1999;19:655e659.3. Stock PG, Roland ME, Carlson L, et al. Kidney and Livertransplantation in human immunodeficiency virus einfectedpatients: a pilot safety and efficacy study. Transplantation.2003;76:370e375.4. Roland ME, Barin B, Carlson L, et al. HIV-Infected liver andkidney transplant recipients: 1- and 3 year outcomes. Am JTransplant. 2008;8:355e365.5. Stock PG, Barin B, Murphy B, et al. Outcomes of kidneytransplantation in HIV-infected recipients. N Engl J Med.2010;363:2004e2201.6. Gruber SA, Doshi MD, Cincotta E, et al. Preliminary experiencewith renal transplantation in HIVþ recipients: low acuterejection and infection rates. Transplantation.2008;86:269e274.7. Kumar MS, Sierka DR, Damask AM, et al. Safety and success ofkidney transplantation and concomitant immunosuppressionin HIV-positive patients. Kidney Int. 2005;67:1622e1629.8. Locke JE, Montgomery RA, Warren DS, et al. Renal Transplantin HIV positive patients: long term outcomes and risk factorsfor graft loss. Arch Surg. 2009;144:83e86.9. Tan PT, Kaczorowski DJ, Basu A, et al. Living-related donorrenal transplantation in HIVþ recipients using alemtuzumabpreconditioning and steroid free tacrolimus monotherapy:a single center preliminary experience. Transplantation.2004;78:1683e1688.10. Frassetto LA, Browne M, Cheng A, et al. Immunosuppressantpharmacokinetics and dosing modifications in HIV-1 infectedliver and kidney transplant recipients. Am J Transplant.2007;7:2816e2820.11. Joan C trullas, Federico Cofan, Montse tuset, et al e renaltransplant in HIV infected patients: 2010 update.12. Pollet C, Paul SM, Morgan R. Immunisations in the HIV-infected patient. N J Med. 2002;99:23e31.a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 5 0 e5 656
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