Case-Based Review

Metabolic Complications of HIV Infection



From the University of Connecticut School of Medicine, Farmington, CT.


  • Objective: To review the metabolic complications of HIV infection.
  • Methods: Review of the literature in the context of 3 clinical cases.
  • Results: People with HIV infection are living longer thanks to the advent of potent antiretroviral therapy. This has led to increased incidence of age-related metabolic complications, including a higher risk of cardiovascular disease, hyperlipidemia, metabolic syndrome, and osteoporosis. Appropriate management of these complications requires an understanding of disease-related and drug-related side effects as well as the potential for drug-drug interactions. A multidisciplinary approach to patient management is most effective.
  • Conclusion: Awareness of the metabolic complications frequently encountered in HIV infection, drug interactions, and possible toxicities is critical to the successful management of HIV-infected individuals.

Key words: HIV; antiretroviral therapy; hyperlipidemia; metabolic syndrome; diabetes; hypogonadism.

According to the most recent data from the Joint United Nations Programme on HIV/AIDS (UNAIDS), 36 million people worldwide are living with HIV/AIDS, with 18 million accessing effective antiretroviral therapy (ART) [1]. The past 2 decades have witnessed enormous advances in the field from prevention to diagnosis and therapeutics, and modern ART largely allows HIV-infected persons to live near-normal life spans [2,3]. However, from the beginning of the epidemic, HIV-infected persons on effective therapy have suffered from myriad metabolic consequences, many of which affect quality of life and result in excess mortality [4]. It is also true that untreated HIV infection portends an increased risk of metabolic complications, likely related to abnormal immune activation, as demonstrated in structured interruption trials [5,6]. It is worth noting, however, that while many of these metabolic dyscrasias and associated risks have historically been attributed primarily to the treatment of HIV infection with ART, data from cohort studies and randomized clinical trials have repeatedly demonstrated significant reductions in morbidity and mortality when ART is initiated early [7]. In this paper, we review HIV-related metabolic complications frequently encountered in clinical practice (hyperlipidemia, diabetes, and bone disease) and best practice considerations in the context of 3 clinical cases.

Case Patient 1

Initial Presentation and History

A 58-year-old male with a history of hypertension and mixed hyperlipidemia is referred for evaluation of newly diagnosed HIV infection. He has no history of intravenous drug use but has had multiple male and female sex partners in the past few years, and requested testing after a partner tested positive. His last negative test was 2 years ago. The patient does not smoke cigarettes. Overall he feels well and tolerates his regimen of lisinopril 10 mg and simvastatin 20 mg daily. On initial evaluation, his exam is unremarkable other than subtle white plaques on the dorsal surface of the tongue and buccal mucosa, and moderate central obesity. Vital signs including blood pressure are normal. Initial laboratory evaluation reveals a CD4 cell count of 150 cells/mm3 and an HIV RNA level of 200,000 copies/mL. Fasting serum total cholesterol is 220 mg/dL, triglycerides 250 mg/dL, LDL 170 mg/dL, and HDL 35 mg/dL. Serum BUN, creatinine, and liver function testing results are normal.

• What initial regimen might be recommended based on the status of his HIV infection and comorbidities?

The most recent iteration of the US Department of Health and Human Services (DHHS) guidelines on use of antiretroviral agents (ARVs) in HIV recommends an initial ART regimen that includes a backbone of 2 nucleoside reverse transcriptase inhibitors (NRTIs), generally tenofovir disoproxil fumarate or tenofovir alafenamide, abacavir (ABC), emtricitabine (FTC), or lamivudine (3TC) [2]. To this backbone should be added a third agent; the majority of those currently recommended are integrase strand transfer inhibitors (INSTIs) (dolutegravir, elvitegravir, raltegravir); one recommended protease inhibitor (PI) (ritonavir-boosted darunavir) is also an option. Some of these initial recommended regimens are available as fixed-dosed combinations in 1 pill, making them attractive options.

The latest guidelines also clearly recommend starting ART in all HIV-infected individuals, irrespective of CD4 count. The patient described above has a very low CD4 count, so there is no question he needs to begin therapy promptly. Given his low CD4 count and relatively high viral load, one may consider a ritonavir-boosted PI as perhaps the most robust option and with a relatively high barrier to resistance development, in contrast to other options. Assuming the patient’s baseline resistance testing reveals a fully sensitive wild-type virus without meaningful resistance mutations, he will begin a regimen of TDF/FTC plus ritonavir-boosted darunavir, 3 pills once daily. Given his low CD4 count (below 200 cells/mm3), he will also need prophylaxis for Pneumocystis jirovecii pneumonia, in the form of trimethoprim/sulfamethoxazole (TMP/SMX) daily. Given the potential for interaction between the boosted PI and simvastatin, his lipid-lowering agent is switched to atorvastatin 10 mg daily.