Tissue donation and virus safety: more nucleic acid amplification testing is needed

A. Pruss, G. Caspari, D.H. Krüger, J. Blümel, C.M. Nübling, L. Gürtler, W.H. Gerlich. Tissue donation and virus safety: more nucleic acid amplification testing is needed.
Transpl Infect Dis 2010: 12: 375–386. All rights reserved Abstract: In tissue and organ transplantation, it is of great importance to avoid the transmission of blood‐borne viruses to the recipient. While serologic testing for anti‐human immunodeficiency virus (HIV)‐1 and ‐2, anti‐hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti‐hepatitis B core antigen (HBc), and Treponema pallidum infection is mandatory, there is until now in most countries no explicit demand for nucleic acid amplification testing (NAT) to detect HIV, hepatitis B virus (HBV), and HCV infection. After a review of reports in the literature on viral transmission events, tissue‐specific issues, and manufacturing and inactivation procedures, we evaluated the significance of HIV, HCV, and HBV detection using NAT in donors of various types of tissues and compared our results with the experiences of blood banking organizations. There is a significant risk of HIV, HCV, and HBV transmission by musculoskeletal tissues because of their high blood content and the high donor–recipient ratio. If no effective virus inactivation procedure for musculoskeletal tissue is applied, donors should be screened using NAT for HIV, HCV, and HBV. Serologically screened cardiovascular tissue carries a very low risk of HIV, HCV, or HBV transmission. Nevertheless, because effective virus inactivation is impossible (retention of tissue morphology) and the donor–recipient ratio may be as high as 1:10, we concluded that NAT should be performed for HIV, HCV, and HBV as an additional safety measure. Although cornea allografts carry the lowest risk of transmitting HIV, HCV, and HBV owing to corneal physiology, morphology, and the epidemiology of corneal diseases, NAT for HCV should still be performed. If the NAT screening of a donor for HIV, HCV, and HBV is negative, quarantine storage of the donor tissue seems dispensable. In view of numerous synergistic effects with transfusion medicine, it would be advantageous for tissue banks to cooperate with blood bank laboratories in performing virological tests.     

Transmission of viral hepatitis by kidney transplantation: donor evaluation and transplant policies (Part 1: hepatitis B virus)

Abstract: This two-part article discusses serologic testing of prospective donors for viral hepatitis B and C as part of the comprehensive donor evaluation and reviews of the current policies and practices aimed at preventing donor-to-recipient transmission of hepatitis B and C viruses (HBV, HBC). This second part of the review discusses HCV. Organs procured from HCV-infected donors can transmit the virus to their recipients. Because a number of studies have associated infections with HCV with increased morbidity and mortality among renal transplant recipients, it is important to prevent HCV transmission with renal transplantation. The majority of organ procurement organizations (OPOs) perform routine screening of organ donors for antibodies to HCV (anti-HCV). The prevalence of HCV infection among cadaver organ donors, ascertained based on a positive anti-HCV test by ELISA2, varies worldwide between 1.08% and 11.8%. The use of kidneys from donors negative for anti-HCV by ELISA2 carries negligible or no risk of transmitting HCV infection. The use of organs from anti-HCV-positive donors has been restricted to life-saving transplants (heart, liver or lung) by the majority of OPOs worldwide. However, discarding kidneys from all anti-HCV positive donors would lead to unnecessary waste of organs because not all anti-HCV positive donors are infectious. Recently, the policy of unconditional restriction on the use of kidneys from anti-HCV positive donors has been challenged, and transplantation of organs from anti-HCV-positive donors into anti-HCV-positive recipients has been found to be safe. An even better alternative might be a policy of transplanting kidneys from anti-HCV-positive donors only in HCV RNA-positive recipients. However, until more data become available, these two strategies remain experimental treatments.     

Organ donor screening using parallel nucleic acid testing allows assessment of transmission risk and assay results in real time

Expansion of the donor pool may lead to utilization of donors with risk factors for viral infections. Donor laboratory screening relies on serological and nucleic acid testing (NAT). The increased sensitivity of NAT in low prevalence populations may result in false‐positive results (FPR) and may cause unnecessary discard of organs.We developed a screening algorithm to deal, in real time, with potential FPR. Three NAT assays: COBAS AmpliScreen assay (CAS), AmpliPrep Total Nucleic Acid Isolation/CAS, and AmpliPrep/TaqMan assays, were validated and used in parallel for prospective screening of increased‐risk donors (IRD), and the probability of FPR was calculated. The lower limit of detection of this algorithm was 9.79, 21.02, and 4.31 IU/mL for human immunodeficiency virus‐1, hepatitis C virus, and hepatitis B virus, respectively, with an average turn‐around‐time of 7.67 h from sample receipt to result reporting. The probability that a donor is potentially infectious with two NAT concordant results was >90%. NAT screening of 35 IRD within 18 months resulted in transplantation of 102 additional organs that without screening would either not be used or used with restrictions in Australia. Using a parallel testing algorithm, real‐time confirmation of seropositive donors allows use of organs from IRD and safer expansion of the donor pool.     

Unexpected hepatitis B virus transmission after liver transplant from nucleic acid testing- and serology-negative liver donors who are hepatitis C viremic

The opioid epidemic has led to increased availability of organs for liver transplantation. The success of direct-acting antiviral therapy for hepatitis C (HCV) has led to the acceptance of HCV viremic donor organs. Nucleic acid testing (NAT) has led to increased detection of HCV and hepatitis B (HBV) in potential donors. A total of 36 patients underwent liver transplantation from donation after brain death donors who were HCV NAT-positive, and three of them were diagnosed with HBV several months after. All three recipients received livers from HCV viremic donors who were negative for HBV by serology and NAT. Soon after liver transplantation, HCV was treated, and all achieved sustained virologic response. They became HBV DNA-positive shortly thereafter. To date, there have been no reported cases of unexpected HBV transmission since universal donor NAT was implemented in 2013. We postulate that the inhibitory effect of HCV viremia on HBV may have prolonged the “NAT window period” in these donors beyond the 20–22 days quoted for solitary HBV infection. These cases highlight the need for more intensive and prolonged screening for HBV in recipients of livers from HCV viremic donors.     

Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the blood supply in the United Kingdom, 1996 to 2003

Several new tests have been recently introduced by the United Kingdom Blood Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply during 1996-2003 has been estimated. These years span the introduction of nucleic acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for HIV. The frequency of an infectious donation entering the blood supply due to i) the window period, ii) assay failures and iii) human and technical errors in testing and processing, was estimated. The window period risk was estimated using the incidence of infection in donors and the length of the window period for tests in use, with an adjustment for atypical inter-donation intervals in seroconverting donors. The estimated frequency of infectious donations entering the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV, HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted HBV, HCV and HIV infection in the UK has been lowered by several improvements to donation testing, although the absolute reduction in risk has been small. Vigilance for errors and the affects of donor selection may be as or more important than further reductions to window periods of tests for improving blood safety with respect to HBV, HCV and HIV.     

HIV Screening Practices for Living Organ Donors, New York State, 2010: Need for Standard Policies

Our survey of kidney and liver transplant centers in New York State found a wide variation among transplant centers in evaluation and screening for HIV risk and infection among prospective living donors. Survey results underscore the need to standardize practices. A recent transmission of human immunodeficiency virus (HIV) from a living donor to a kidney recipient revealed a possible limitation in existing screening protocols for HIV infection in living donors. We surveyed kidney and liver transplant centers (N?=?18) in New York State to assess HIV screening protocols for living donors. Although most transplant centers evaluated HIV risk behaviors in living donors, evaluation practices varied widely, as did the extent of HIV testing and prevention counseling. All centers screened living donors for serologic evidence of HIV infection, either during initial evaluation or ≥1 month before surgery; however, only 50% of transplant centers repeated HIV testing within 14 days before surgery for all donors or donors with specific risk behaviors. Forty-four percent of transplant centers used HIV nucleic acid testing (NAT) to screen either all donors or donors with recognized risk behaviors, and 55% never performed HIV NAT. Results suggest the need to standardize evaluation of HIV risk behaviors and prevention counseling in New York State to prevent acquisition of HIV by prospective living organ donors, and to conduct HIV antibody testing and NAT as close to the time of donation as possible to prevent HIV transmission to recipients.     

No increased mortality from donor or recipient hepatitis B‐ and/or hepatitis C‐positive serostatus after related‐donor allogeneic hematopoietic cell transplantation

Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen‐identical related‐donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow‐up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment‐related mortality, survival, graft‐versus‐host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.     

Reduction of the risk of transfusion‐transmitted viral infection by nucleic acid amplification testing in the Western Cape of South Africa: a 5‐year review

Background and Objectives In October 2005, individual donation nucleic acid amplification testing (ID‐NAT) for HIV, HBV and HCV was introduced in the Western Cape Province of South Africa. After 5 years, the impact on HIV, HBV and HCV transmission risk was assessed. Materials and Methods A total of 649 745 donations were tested by ID‐NAT using the Ultrio assay on the Tigris instrument (Novartis Diagnostics) and for anti‐HIV, HBsAg and anti‐HCV (Abbott Prism). Initial reactive samples were repeated in duplicate. Discrepant repeat reactive samples were subjected to confirmatory assays. ID‐NAT nonrepeat reactive donations were further screened for occult HBV infection (OBI) by anti‐HBc assay. Results ID‐NAT yielded 6 HIV‐RNA‐positive donations in the anti‐HIV‐negative window period (WP) but only 2 were p24 Ag nonreactive (1:325 000). Mathematical modelling estimated a similar HIV transmission risk for lapsed and repeat donations, in the order of 3 per million. The WP risk for HBV was 13 per million. Eight acute (1:81 000) and 13 chronic OBI yield cases (1:50 000) were interdicted. There were significantly more anti‐HBc‐positive donors in the Ultrio initial reactive/nonrepeat reactive group (12%) than in an Ultrio nonreactive control group (6%). Conclusion ID‐NAT in the Western Cape Province of South Africa has contributed significantly to enhancing blood safety, particularly for HBV transmission risk and to a lesser extent for HIV. Anti‐HBc testing of NAT nonrepeat reactive donations seems useful in identifying a subgroup of donors with OBI who may be at risk of transmitting HBV.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

A prospective study of transfusion-transmitted virus transmission by blood transfusion

Recently, a new single-stranded DNA virus (TT virus, TTV) has been isolated and related to post-transfusion hepatitis. The aim of this study was to investigate the prevalence of TTV in blood donors and blood recipients, and the incidence of TTV transmission by blood transfusion. TTV DNA and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV), were examined in 130 blood recipients, and the presence of TTV was studied in their 340 corresponding blood donors. The prevalence of TTV infection was 10.6% (36/340) in donors and 8.5% (11/130) in blood recipients, before transfusion. Eighteen subjects (15.1%) were found to be TTV positive, after transfusion, in the 119 blood recipients without TTV before transfusion; at least one of the corresponding donors was TTV positive. There were 46 subjects with post-transfusion hepatitis virus infection, 45 with HCV infection (including seven co-infected with TTV) and two with HBV infection (including one co-infected with HCV and one co-infected with TTV). The recipient with TTV and HBV co-infection and three of the seven patients with TTV and HCV infection had alanine aminotransferase (ALT) levels higher than 90Ul^–1, but only two of the 10 isolated TTV infections had a mild ALT elevation. These results show that prevalence of TTV was high in blood donors and hospitalized patients, and isolated TTV infection is not related to significant ALT elevation.     

Current practices and evaluation of screening solid organ donors for West Nile virus

The first cases of West Nile virus (WNV) transmitted through solid organ transplantation (SOT) were identified in 2002. Subsequently, 5 additional clusters have been reported to public health officials in the United States. Based upon a limited number of known cases, patients who acquire WNV from infected donor organs might be at higher risk for severe neurologic disease and death, compared with patients infected through mosquito bites. In response, some organ procurement organizations (OPOs) have instituted pre‐transplant screening of organ donors for WNV infection. We evaluated the current practices, concerns, and challenges related to screening organ donors for WNV in the United States by reviewing the relevant medical literature and interviewing key stakeholders. Screening organ donors for WNV is not required by national policy. In 2008, 11 (19%) of 58 OPOs performed WNV screening using nucleic acid amplification testing (NAT). These OPOs differ in their screening strategies, NAT performed, and logistical challenges. Concerns of delays in receiving NAT results before transplant and potential false‐positive results leading to organ wasting are limitations to more widespread screening. Furthermore, it is unknown if WNV screening practices decrease SOT‐related morbidity and mortality, or if screening is cost‐effective. Additional data are needed to assess and improve transplant outcomes related to WNV.     

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections

Background The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion‐transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Study Design and Methods Post‐transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre‐transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre‐transfusion specimen was non‐reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti‐HBc titres or high anti‐HBc with high anti‐HBs titres. Results Transfusion‐transmitted HCV and HIV infections were not observed. One case of post‐transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451–41 841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty‐four anti‐HBc‐ and/or anti‐HBs‐reactive blood components were transfused to 52 patients non‐reactive for anti‐HBc or anti‐HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). Conclusion This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.     

Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic acid amplification testing

Blood and plasma donations in Germany are collected by several institutions, namely the German Red Cross, community and hospital-based blood services, private blood centres, commercial plasma donation sites and transfusion services of the army. All blood donation centres are required to report quarterly data on infection markers to the Robert Koch Institute, thus providing current and accurate epidemiological data. The prevalence and incidence of relevant viral infections are low in the blood donor population in Germany, with a decreasing trend for hepatitis C infections in new and repeat donors since 1997. The implementation of mandatory nucleic acid amplification technique (NAT) testing for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV-NAT became mandatory in 2004 but was done voluntarily by the majority of the blood donation services before then. The potential benefit of hepatitis B virus (HBV) minipool NAT is not as clear because chronic HBV carriers with very low virus levels might donate unidentified. The residual risk of an infectious window period donation inadvertently entering the blood supply can be estimated using a mathematic model which multiplies the incidence rate by the number of days during which an infection may be present but not detectable, i.e. the length of the window period. The risk of an undetected infection without NAT testing was estimated to be 1 in 2,770,000 for HIV, 1 in 670,000 for HCV and 1 in 230,000 for HBV in 2001/2002. This contrasts with 1 in 5,540,000 for HIV, 1 in 4,400,000 for HCV and 1 in 620,000 for HBV with minipool NAT testing. This demonstrates that NAT testing can further reduce the already very small risk of infectious donations entering the blood supply.     

Donor screening for hepatitis B virus infection in a cell and tissue bank

Abstract: Background and objectives. Hepatitis B virus (HBV) has been transmitted by tissue transplantation. In order to reduce the risk of HBV transmission, testing for antibody to HBV core antigen (anti‐HBc) is used in addition to testing for hepatitis B surface antigen (HBsAg) in many blood centers and tissue banks. Design and methods. We retrospectively analyzed the results of HBV assays in tissue donors. All tissue donors were tested for HBsAg and anti‐HBc. All anti‐HBc positive sera were tested for the antibody to HBsAg (anti‐HBs). From July 2006, an HBV nucleic acid testing (NAT) assay was also performed. Results. A total of 6855 tissue donors from January 1999 till July 2007 were tested for HBV assays: 4756 women and 2099 men. Positive HBsAg was found in 23 (0.36%) living donors, while no multiorgan or cord blood (CB) donor was found to be positive for HBsAg. Positive anti‐HBc was found in 80 multiorgan donors (12.94%), 599 living donors (17.84%), and 103 CB donors (3.57%) (P<0.005), while isolated anti‐HBc was found in 12 multiorgan (1.94%), in 126 living tissue donors (3.75%), and in 8 CB donors (0.28%). A total of 1310 donors were analyzed for single‐sample DNA HBV NAT assay. Discussion. We consider that anti‐HBc and NAT assays must both still be performed in addition to HBsAg assay for HBV screening in tissue donors. All these tests will be useful in order to define an algorithm for safe and efficient management of the tissue bank.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century

In the past, transfusion-transmitted virus (TTV) infections were not uncommon. In recent years with advanced technologies and improved donor screening, the risk of viral transfusion transmission has been markedly reduced. Hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have all shown marked reduction in transmission rates. However, the newer technologies, including nucleic acid technology (NAT) testing, have affected the residual rates differently for these virally transmitted diseases. Zero risk, which has been the goal, has yet to be achieved. False negatives still persist, and transmissions of these viruses still occur, although rarely. It is known that HBV serological testing misses some infected units; likewise, HBV NAT-negative units have also been known to transmit the virus. Similarly, HIV minipool NAT-negative units have transmitted HIV, as recently as 2007; likely, these transmissions would have been prevented with single-unit NAT testing. Newer technologies, such as pathogen inactivation (PI), will (ideally) eliminate these falsely test negative components, regardless of the original testing method used for detecting the viruses.     

Donor derived hepatitis B virus infection: Analysis of the Organ Procurement & Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009‐2017. Proven, probable or possible transmission of HBV occurred in 25 (23.8%) cases. Recipients of liver grafts were most commonly infected (20 of 21 exposed recipients) compared to 9 of 21 exposed non‐hepatic recipients. Eleven of 25 donors were HBV core antibody (HBcAb) positive/HBV surface antigen (HBsAg) negative and infected 8/20 recipients. Of the 10 liver recipients and 1 liver‐kidney recipient who received organs from these donors: six were not given antiviral prophylaxis, two developed infection after antiviral prophylaxis was discontinued, two developed HBV while on lamivudine prophylaxis, one was on antiviral prophylaxis and did not develop HBV viremia or antigenemia. One recipient of a HBcAb positive/HBsAg negative kidney developed active HBV infection. Unexpected donor‐derived transmission of HBV was a rare event in reports to DTAC, but was often detected in the recipient late post‐transplant. Six of 11 recipients (54.5%) of a liver from a HBcAb positive donor did not receive prophylaxis; all of these were potentially preventable with the use of anti‐viral prophylaxis.     

Cost-effectiveness of nucleic acid test screening of volunteer blood donations for hepatitis B, hepatitis C and human immunodeficiency virus in the United States

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the cost-effectiveness of adding nucleic acid testing (NAT) to serological (antibody and antigen) screening protocols for donated blood in the United States (US) with the purpose of reducing the risks of transfusion-transmission of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). MATERIALS AND METHODS: The costs, health consequences and cost-effectiveness of adding either minipool or individual-donor NAT to serological screening (SS) testing were estimated using a decision-analysis model. RESULTS: With the given modelling assumptions, adding minipool NAT would avoid an estimated 37, 128 and eight cases of HBV, HCV and HIV, respectively, and save approximately 53 additional years of life and 102 additional quality adjusted life years (QALYs) compared with SS, at a net cost of $154 million. SS + minipool NAT - p24 compared with SS alone resulted in an incremental cost-effectiveness ratio of $1.5 million per QALY gained (range in sensitivity analysis $1.0-2.1 million per QALY gained) in this US analysis. CONCLUSIONS: The cost effectiveness of adding NAT screening is outside the typical range for most healthcare interventions, but not for established blood safety measures.     

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia

Introduction

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood.

Methods

Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid‐lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use were assessed by multivariate logistic regression.

Results

A total of 1587 HIV‐monoinfected, 190 HIV/HBV‐coinfected and 255 HIV/HCV‐coinfected patients were evaluated. Most were male (85–92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44–56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120–370) cells/μL in HIV‐monoinfected participants, 195 (110–330) cells/μL in HIV/HBV‐coinfected participants and 268 (140–409) cells/μL in HIV/HCV‐coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001).

Conclusions

HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART‐related hyperlipidaemia.