This edition of Clinical issues in HIV addresses some of the complexities faced by physicians in treating patients infected with HIV in the era of highly effective antiretroviral therapy (ART). The case by Bruce Hendry will resonate as a common problem faced by HIV teams and GPs caring for an ageing population, where patients’ kidney function is approaching, but has not reached, chronic kidney disease (CKD) stage 3. As our HIV patients age, their co-morbidities increase, as is the case for their non-HIV infected peers; however, unlike their peers, they have the additional confounding problems of potential or actual toxicities of their ARTs.
HIV treatment regimens with a nucleotide reverse transcriptase inhibitor (NRTI) backbone are the standard and preferred options of antiretroviral therapy (ART) according to key global guidelines, including those from the British HIV Association (BHIVA). This means that, at present, most ART regimens are based on a tenofovir – as tenofovir disoproxil fumarate (TDF) – or abacavir backbone. Patients with a modest loss of renal function (estimated glomerular filtration rate [eGFR] 60–75 ml/min/1.73 m2) present a particular challenge, as both of those NRTI strategies are associated with potential problems. TDF has an established risk profile for the development of renal toxicity, observed in around 1–2% of the total HIV population, and this risk is increased in those with a moderate eGFR reduction. Abacavir has been associated with an increased risk of cardiovascular (CV) events, particularly in those with CV disease (CVD) risk factors at baseline. An eGFR <75 ml/min/1.73 m2 is itself a CVD risk factor.
In the era of combination antiretroviral therapy (cART), liver disease and non-Hodgkin’s lymphoma (NHL) are among the most frequent causes of death in people living with HIV (PLWHIV). Not only is HIV linked with an increased risk of NHL, but the hepatitis C virus (HCV) has also been associated with lymphomagenesis in the general population, as well as in cohorts of PLWHIV. Numerous studies have shown that concomitant cART with systemic chemotherapy improves outcomes in those with HIV-associated NHL. However, this approach leads to a fall in cluster of differentiation 4 (CD4) counts, predisposing to opportunistic infections and reactivating latent viruses, as well as to significant drug–drug interactions (DDIs). Furthermore, direct-acting antivirals (DAAs) that are used to treat HCV have been shown to reduce relapse of NHL among HCV mono-infected individuals. Thus, there are formidable pharmacological challenges in simultaneously treating HIV, HCV and NHL along with opportunistic infection prophylaxis.