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HIV-Associated Complications: A Systems-Based Approach

Ecler Ercole Jaqua, MD, MBA, DipABOM
Mai-Linh N. Tran, MD, DipABLM, DipABOM
Prashanth Bhat, MD, MPH

American Family Physician. 2026;113(1):71-79.

Author disclosure: No relevant financial relationships.

This clinical content conforms to AAFP criteria for CME.

Antiretroviral therapy has transformed HIV into a chronic condition, enabling many people living with HIV to achieve near-normal life expectancy. However, HIV-associated complications remain common, driven by persistent immune activation, inflammation, sedentary lifestyle, and poor diet with cardiometabolic issues such as dyslipidemia, insulin resistance, body composition changes, and osteoporosis among the most prevalent. Newer antiretroviral therapy regimens, particularly integrase strand transfer inhibitor–based therapies, are better tolerated and typically associated with fewer systemic complications compared with previous therapy options. Neurocognitive impairment persists despite viral suppression and requires ongoing assessment and support. Distal sensory polyneuropathy affects up to 60% of people living with HIV, with evidence supporting treatment using gabapentin and capsaicin and possibly alpha-lipoic acid and medical cannabis in select cases. Chronic kidney disease is commonly driven by hypertension or diabetes. Rising sexually transmitted infection rates highlight the necessity of sexual health counseling and interventions such as doxycycline postexposure prophylaxis. Noninfectious pulmonary conditions such as chronic obstructive pulmonary disease and pulmonary hypertension remain underrecognized. Gastrointestinal complications are common and often worsen as CD4 counts decline. Dermatologic and hematologic complications, including cytopenias and clonal hematopoiesis, are associated with increased cancer risk. Primary care clinicians play a critical role of caring for a patient with HIV through routine screening, lifestyle counseling, and coordinated care.

Advancements in antiretroviral therapy (ART) have dramatically improved life expectancy for people living with HIV.1 Life expectancy for those with high CD4 counts taking effective ART is now nearly comparable with that of the general population, regardless of when treatment was initiated.1 However, despite these gains, individuals with HIV continue to experience a range of chronic complications that affect multiple organ systems. These complications are primarily driven by persistent immune activation and chronic inflammation, even in the context of viral suppression.2 Contributing factors include low nadir CD4 counts, aging, smoking, physical inactivity, unhealthy diets, and, in some cases, ART exposure— particularly with earlier regimens.2 Chronic immune dysregulation, with elevated interleukin-6 (IL-6) and D dimer, increases comorbidities not related to AIDS and mortality in HIV.3

WHAT'S NEW ON THIS TOPIC

Life expectancy for those taking effective antiretroviral therapy with high CD4 counts is now nearly comparable with that of the general population, regardless of when treatment was initiated.
The REPRIEVE trial demonstrated a 35% reduction in major cardiovascular events with statin use among people living with HIV 40 to 75 years of age at low to moderate risk, with a number needed to treat of 82 over 5 years.
People living with HIV have a 10% to 50% higher fracture risk and experience osteoporotic fractures up to a decade earlier than the general population.
Dialysis and kidney transplant outcomes in people living with HIV with virologic suppression are now comparable with those without HIV.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments
Statins are recommended for primary cardiovascular disease prevention, including pitavastatin, atorvastatin, and rosuvastatin, in individuals with HIV 40 to 75 years of age at low to moderate atherosclerotic cardiovascular disease risk.6,11 BREPRIEVE trial and 2024 US Department of Health and Human Services, including expert consensus and data from randomized controlled trials
Screening for osteoporosis with dual energy x-ray absorptiometry in individuals with HIV is recommended for women who are post-menopausal, men 50 years and older, and younger individuals with risk factors, such as low body mass index, smoking, alcohol use, prior fractures, or hepatitis C virus coinfection.17,19 CExpert consensus from cohort studies and HIV primary care guidelines
HIV-associated neurocognitive impairment should be assessed with neurocognitive screening using clinical history and cognitive tests and also imaging when indicated.21,22 CExpert consensus and updated recommendations
Gabapentin and capsaicin 8% patches are recommended for managing HIV-associated distal sensory polyneuropathy; other options include alpha-lipoic acid, medical cannabis, exercise, and stopping neurotoxic antiretroviral therapy.24,25 CHIV Medicine Association of the Infectious Diseases Society of America guidelines and supporting observational studies
Annual screening for chronic kidney disease with estimated glomerular filtration rate and urine albumin-to-creatinine ratio is recommended for people with HIV.27 CHIV Medicine Association of the Infectious Diseases Society of America guidelines for HIV-associated chronic kidney disease
Comprehensive STI screening, sexual health counseling, and the use of DoxyPEP for men who have sex with men and transgender women are recommended to reduce STI transmission in people with HIV.33 CCenters for Disease Control and Prevention STI guidelines and recent evidence supporting DoxyPEP effectiveness
Offer HPV vaccination up to 45 years of age and screen high-risk individuals* with anal cytology or anoscopy based on risk factors.9,10 CHIV Medicine Association of the Infectious Diseases Society of America and International Anal Neoplasia Society guidelines for cancer prevention in HIV

DoxyPEP = doxycycline postexposure prophylaxis; HPV = human papillomavirus; STI = sexually transmitted infection.

*—High-risk individuals include men who have sex with men, transgender women, people with HIV (especially with low CD4 counts), individuals with prior anogenital warts, women with a history of high-grade cervical or vulvar dysplasia, and those with persistent HPV infection.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

ECLER ERCOLE JAQUA, MD, MBA, FAAFP, AGSF, FACLM, DipABOM, AAHIVS, is an associate professor in the Department of Family Medicine, San Antonio Regional Hospital, Upland, California.

MAI-LINH N. TRAN, MD, FAAFP, DipABLM, DipABOM, AAHIVS, is an assistant professor in the Department of Family Medicine, Loma Linda University School of Medicine, Loma Linda, California.

PRASHANTH BHAT, MD, MPH, AAHIVS, is an associate program director at the Baptist Memorial Hospital Family Medicine Residency Program, Memphis, Tennessee.

Address correspondence to Ecler Ercole Jaqua, MD, MBA, FAAFP, AGSF, FACLM, DipABOM, AAHIVS at eclerjaqua@gmail.com.

Author disclosure: No relevant financial relationships.

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