Table 3 HIV and related complications
From: Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis
Study | HAART regimen | Pharmacokinetic changes | Mean CD4 T-cell counts pre-TX (cells/μL) | Mean CD4 T-cell counts post-TX | Prophylaxis against opportunistic infection | Infectious complications | Post-transplant neoplasia |
|---|---|---|---|---|---|---|---|
Roland (2008) | Varied (zidovudine and stavudine avoided) | Not specified | 439 (293–613) | Not specified | OI prophylaxis included life-long trimethoprim-sulfamethoxazole, dapsone or atovaquone to prevent Pneumocystis carinii pneumonia (PCP), brief antifungal prophylaxis using fluconazole, and Cytomegalovirus (CMV) prophylaxis with either acyclovir or valcyte, depending upon the recipient and donor CMV status | Candida esophagitis(1); CMV(1) | Not specified |
Touzot (2010) | Not specified | Because of persistent high trough level of CNI, protease inhibitor treatment was stopped in nine patients during the first week of posttransplantation and in five others during the follow-up | 386 | 545 (3Â months) 534 (6Â months) 460 (12Â months) 569 (24Â months) | Patients received ganciclovir or valgangyclovir for cytomegalovirus and trimethoprim/sulfamethoxazole for Pneumocystis jirovecii, for at least 6Â months. For patients with a past history of tuberculosis, Isoniazid was added for 9Â months | Pyelonephritis(18) Pneumonia(5) Septic shock(1) Others(4) CMV(2) BK virus(1) | Lymphoma(1) |
Mazuecos (2006) | Varied | Not specified | ≥ 200 | 670 ± 481 | Not specified | Pneumonia(3) VZV(1) | Not specified |
Stock (2003) | Varied | Not specified | 423 ± 93 | 419 ± 287 | Standard prophylaxis for Pneumocystis, cytomegalovirus (CMV), and fungal infections were used according to standard transplant protocols | Staphylococcus aureus wound infection(2) Haemophilus influenza bacterial pneumonia(1) S. aureus endocarditis(1) | Not specified |
Stock (2010) | Protease-inhibitor–based(63) NNRTI-based(59) Protease-inhibitor-based and NNRTI-based(15) Nucleoside analogues only(5) Nucleoside analogues only(6) None(2) | Not specified | 524 | Not specified | Prophylaxis against opportunistic infection included lifelong therapy to prevent Pneumocystis jirovecii pneumonia, fluconazole for antifungal prophylaxis, and valganciclovir or ganciclovir to prevent cytomegalovirus infection. Macrolide prophylaxis against Mycobacterium avium complex was required when the CD4+ T-cell count dropped below 75 cells per cubic millimeter | Pseudomonas aeruginosa sepsis(1) | Renal-cell carcinoma(2) Kaposi’s sarcoma(2) Oral squamous-cell carcinoma(2) Squamous-cell skin cancer(1) Basal-cell skin cancer(1) Thyroid gland cancer(1) |
Kumar (2004) | Varied | All patients continued their HAART regimens. | ≥ 200 | ≥ 400 | Infection prophylaxis was ganciclovir or valgancyclovir for cytomegalovirus, trimethoprim/sulfamethoxazole or dapsone for Pneumocystis carinii, and nystatin for oral and esophageal thrush for 200 days after transplantation | Sepsis(1) Chest infection(2) Necrotizing fasciitis(1) Infection of lymphocoele(1) Admitted urinary tract infection(9) | Not specified |
Qiu (2006) | Not specified | Not specified | Not specified | Not specified | Not specified | Bacterial pneumonia(1) | Not specified |
Tan (2004) | Varied | Not specified | 589 ± 313 946 ± 800 | 424 ± 384 | Not specified | Plantar fasciitis(1) | Basal cell carcinoma |
Carter (2006) | Not specified | Patients resumed their pre-transplant HAART therapy when an oral diet was started, typically 1 or 2 days after transplant. | Not specified | Not specified | Varied | Candida oesophagitis(1) S. aureus endocarditis with septic embolization(1) Streptococcus viridans bacteraemia(1) Pseudomonas pneumonia with multi-organ failure(1) Escherichia coli urosepsis(1) Culture-negative urosepsis(1) Enterococcus bacteraemia(1) Polymicrobial pneumonia sepsis(1) Clostridium difficile colitis(1) Diverticulitis and secondary bacterial peritonitis(1) Influenza, bacterial pneumonia(1) Pseudomonas pneumonia(1) | Not specified |
Gruber (2008) | All recipients were maintained on at least two nucleoside reverse transcriptase inhibitors, three in combination with a ritonavir-boosted protease inhibitor (PI), two in combination with a non-boosted PI, and two in combination with nevirapine (a nonnucleoside reverse transcriptase inhibitor) | Not specified | ≥ 200 | ≥ 200 | Antimicrobial prophylaxis was initiated within the first 24 to 48 h after surgery. All patients received trimethoprim/sulfamethoxazole one single-strength daily for 6 months and nystatin 5 mL four times per day for 1 month. Cytomegalovirus prophylaxis was administered depending on the patient’s risk-stratified profile | CMV(1) Pneumonia(1) Urinary tract infection(3) | Not specified |
Gómez (2013) | Not specified | Protease inhibitor treatment was stopped with substitution of the integrase inhibitor Raltegravir | 504 | 373.5 (3 months) 488 (6 months) | Patients received trimethoprim–sulfamethoxazole for Pneumocystis jiroveccii | Not specified | Epstein–Barr virus high grade-related B-cell lymphoma(1) |
Izzo (2017) | Not specified | To avoid PK interactions, cART was modified from a PI/ NNRTI-based to an InSTI-based regimen in 11/20 patients alive with functioning graft (65%); 7/11 were switched to raltegravir and 4/11 were switched to dolutegravir. 7/20 (35%) were on treatment with a cART regimen including both InSTI and PI/ritonavir (RTV) or efavirenz (EFV) at the end of follow-up | 337 | 400 | Not specified | Pneumonia and urinary tract infections were the most common diagnosis | Skin Kaposi’s sarcoma(2) Colorectal cancer(1) |
Roland (2004) |  |  | 441 (200–1054) | 436 (3–975) | Not specified | Candida esophagitis(1); Staphylococcal sepsis(1) | Not specified |
Gasser (2009) | ART consisted of nucleoside/nucleotide reverse transcriptase inhibitors (RTI) and/or non-nucleoside RTI and/or protease inhibitors, mostly combined as a three-class therapy | Not specified | 483 | Not specified | Not specified | Not specified | Not specified |
Gathogo (2014) | Antiretroviral therapy was stratified as containing ritonavir-boosted protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTI) or other (regimens containing nucleoside/nucleotide reverse transcriptase with or without integrase inhibitors) | Not specified | 366 | Not specified | Regarding the management and prevention of cytomegalovirus (CMV) infection, some centres routinely administered valganciclovir prophylaxis for 3 months posttransplantation (irrespective of donor/recipient CMV IgG status), while others prescribed CMV prophylaxis to recipients of grafts from CMV IgG-positive donors or combined regular posttransplant CMV surveillance with preemptive valganciclovir treatment if the CMV viral load exceeded 3–4000 copies/mL | Urinary tract infection(10) Pneumonia(5) Cellulitis(2) Pyrexia of unknown origin(1) Herpes simplex viral encephalitis(1) | Not specified |
Baisi (2016) | To avoid drug interactions between protease inhibitors and IS, ARV was given in the immediate post-operative period with enfuvirtide in combination with 2 nucleoside analogues or 1 nucleoside analogue and raltegravir (RAL), which was administered within 48 h | Once steady state of IS was achieved (on average, pod 30), T20 was stopped and HAART was modified on the basis of HIV pre-transplant genotype profile, individual drug tolerability, and clinical conditions | 441 | Not specified | For Pneumocystis jirovecii prophylaxis, we used a 6 month course of trimethoprim–sulfametoxazol. For CMV prophylaxis, all patients received IV ganciclovir or oral valganciclovir for a 3-month treatment; in the case of donor/recipient CMV status, specific anti-CMV immunoglobulins were added | Not specified | No neoplasms were reported |
Xia (2014) | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified |
Locke (2015) | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified |
Abbott (2004) | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified |
Cristelli (2017) Brazil | Non-boosted protease-inhibitor(2) Boosted protease inhibitor(16) NNRTI(20) Nucleoside analogs only(2) | Need for antiretroviral changes(14) Drug interactions with CNI/mTORi(3) Therapeutic failure(5) Adverse events(4) Unavailable drug(1) Unclear reason(1) | > 200 | 356 (3 months) 502 (1 year) 556 (3 years) | All patients received prophylactic trimethoprim/sulfa-methoxazole against Pneumocystis jirovecii and toxoplasmosis for at least 6 months | Surgical site(5) Urinary tract(13) Respiratory tract(15) Cytomegalovirus(7) Varicella-zoster virus(6) Esophageal candidiasis(5) | Non-skin cancer(1) |
Cristelli (2017) Spain | Non-boosted protease-inhibitor(2) Boosted protease inhibitor(5) NNRTI(4) Integrase inhibitor(4) | Need for antiretroviral changes(9); Drug interactions with CNI/mTORi(8); Unclear reason(1) | > 200 | 403 (3 months) 491 (1 year) 456(3 years) | All patients received prophylactic trimethoprim/sulfamethoxazole against Pneumocystis jirovecii and toxoplasmosis for at least 6 months | Surgical site(1) Urinary tract(5) Respiratory tract(3) Cytomegalovirus(1) | Non-skin cancer(2) |
Mazuecos (2013) | Not specified | A trend was observed to increase non-nucleoside reverse transcriptase inhibitors use, although without significant differences at the end of the study. Protease inhibitors continued to be administered after KT, but their use dropped significantly at the end. On the contrary, the use of integrase inhibitor (raltegravir) increased most significantly after KT, and that increase was maintained at the end of the study, suggesting a good tolerance to the drug | 420 | 413 (1 month) 497 (3 months) 570 (1 year) 627 (2 years) 618 (3 years) | The main prophylactic therapies for infections included trimethoprim–sulfamethoxazole for Pneumocystis (at least 6 months), ganciclovir/valganciclovir for cytomegalovirus (at least 3 months) and isoniazid for patients with a past history of tuberculosis (9 months) | Bacterial infection(41) Fungal infection(2) Viral infection(6) | Skin carcinoma(3) Kaposi’s sarcoma(1) Lymphoproliferative disorder(1) |
Rosa (2016) | The three most common regimens post-transplant were nucleoside reverse transcriptase inhibitors (NRTI) plus PI, NRTI plus INSTI, and NRTI plus NNRTI | A total of 30 (52%) patients underwent ART modifications after transplan | 546.07 ± 271.04 | 318.54 ± 240.73 (12 months) 374.14 ± 235.68 (26 months) 401.57 ± 283.71 (52 months) | Not specified | CMV(11) Others not specified | Not specified |
Vicari(2016) | Reverse transcriptase inhibitors were used for all patients, Non-nucleoside reverse transcriptase inhibitors were used by 29 patients, and protease inhibitors were used by 21 patients | Not specified | 577.3 ± 333.5 | 610.3 ± 318.5 | Not specified | Bacterial infection(55) Cytomegalovirus infection(39) Polyoma virus infection(7) Other viral infections(8) (Include herpes simplex, varicella zoster, adenovirus, and dengue) | Not specified |
Bossini (2014) | The HAART regimen was protease inhibitor (PI)-based in 10 cases and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in the last two patients | Antiretroviral therapy was temporarily interrupted on the day of transplantation and restarted within 4 days. Only two patients remained without HAART after transplantation because they maintained an adequate immunological and virological control | 352 ± 174 | 352 ± 174 (1 year) | Trimethoprim–sulfamethoxazole for 6 months | Pneumonia(5) HSV 2 genitalis(1) Malaria(1) CMV infectious(3) UTI(3) Epididymitis(2) Esophageal candidiasis(1) BKVN(1) | Kaposi’s sarcoma(1) |
Mazuecos (2011) | Not specified | Two patients remained without HAART after transplantation because they maintained an adequate immunological andvirological control | > 200 | > 200 | Not specified | Bacterial(10) Mycotic(1) CMV(1) Other virus(2) | Lymphoma(1) |
Gathogo (2016) | PI/r containing(30) NNRTI containing(40) Integrase inhibitor containing Raltegravir(23) | Not specified | 366 | Not specified | Not specified | Not specified | Not specified |
Malat (2018) | Varied | Not specified | ≥ 200 | Not specified | Not specified | Not specified | Not specified |