In a person with HIV who has a good CD4 count (>500 cells/µL), what complications can still occur?

Complications of HIV Despite Good CD4 Count (>500 cells/µL)

Even with a good CD4 count above 500 cells/µL, HIV-positive individuals remain at risk for cardiovascular disease, non-AIDS malignancies, bacterial infections, tuberculosis, and metabolic complications—conditions that require ongoing vigilance regardless of immune status.

Cardiovascular and Metabolic Complications

Despite preserved immunity, HIV-positive patients with good CD4 counts face elevated cardiovascular risk. The presence of multiple cardiac risk factors should influence clinical decision-making, as untreated HIV infection itself is associated with cardiovascular events 1. These complications occur through chronic inflammation and immune activation that persist even with viral suppression 2.

Key metabolic concerns include:

• Lipid abnormalities and atherosclerotic disease, particularly in patients with family history of early coronary heart disease 1
• Diabetes mellitus and hypertension, which compound cardiovascular risk 1
• Drug-related lipohypertrophy (dorsocervical fat pad, gynecomastia, visceral abdominal fat) and lipoatrophy (loss of subcutaneous fat in face, extremities, buttocks) from antiretroviral therapy 1

Non-AIDS Malignancies

Current CD4 count remains strongly associated with infection-related non-AIDS malignancies even in higher CD4 strata 2. The incidence of AIDS-defining illnesses, particularly malignant types, remains elevated until CD4 counts exceed 750 cells/µL 3.

Specific malignancies to monitor:

• Kaposi's sarcoma and non-Hodgkin's lymphoma can occur at any CD4 level, though risk decreases with higher counts 4
• Cervical cancer in women requires regular screening with careful pelvic examination and visual inspection 1
• Anal cancer necessitates anogenital examination for condylomata and other lesions 1

Bacterial and Opportunistic Infections at Higher CD4 Counts

Bacterial pneumonia (Streptococcus pneumoniae, Haemophilus influenzae) remains the most common pneumonia at any CD4 level 5. Several infections do not follow typical immunosuppression patterns:

• Tuberculosis can manifest at any CD4 count, though risk increases significantly below 300 cells/µL 5, 6
• Herpes zoster and pneumococcal infections occur even with CD4 >200 cells/µL 5, 6
• Recurrent mucocutaneous herpes simplex and oral candidiasis increase in frequency as CD4 drops below 500 cells/µL 4

Hepatic and Renal Complications

Latest CD4 count is strongly associated with serious hepatic events 2. HIV-infected patients require monitoring for:

• Hepatomegaly or splenomegaly, which may indicate infection or malignancy 1
• Chronic kidney disease, particularly in patients of African ancestry with APOL1 high-risk variants 1
• HIV-associated nephropathy (HIVAN) and HIV immune complex kidney disease (HIVICK), which can occur despite good CD4 counts 1

Neurological and Psychiatric Complications

Neurological complications persist across CD4 strata:

• Neurocognitive disorders and HIV-associated dementia require neuropsychology referral for assessment 1
• Peripheral neuropathies necessitate careful neurological examination 1
• Depression occurs at twice the rate in HIV-infected women compared to men, particularly with history of violence or victimization 1
• Changes in mood, libido, sleeping patterns, appetite, concentration, and memory should be systematically assessed 1

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS typically occurs within 3-6 months after ART initiation, with CD4 <50 cells/µL at ART start being a major risk factor 5, 7. However, paradoxical worsening can occur even in patients who subsequently achieve good CD4 counts:

• Mycobacterium tuberculosis IRIS presents with high fevers, worsening respiratory symptoms, and enlarging lymphadenopathy 7
• Cryptococcus neoformans IRIS manifests with increased intracranial pressure and worsening meningeal inflammation 7
• MAC IRIS causes paradoxical worsening despite appropriate antimycobacterial therapy 7

Critical Monitoring Considerations

A higher latest CD4 count is associated with lower short-term risk of serious non-AIDS events even in CD4 strata >350 cells/µL 2. However, immune reconstitution is not complete until CD4 increases to >750 cells/µL 3.

Essential monitoring includes:

• CD4 counts every 3-6 months to track immune function 1
• Comprehensive cardiopulmonary examination including peripheral vascular disease assessment 1
• Screening for sexually transmitted infections and counseling on transmission prevention 1
• Regular ophthalmologic examination in patients with history of advanced disease 1
• Baseline organ function assessment and screening for coinfections 1

Common Pitfalls to Avoid

• Never assume good CD4 count eliminates all HIV-related complications—cardiovascular disease, malignancies, and certain infections occur independently of CD4 level 1, 5, 2
• Do not overlook depression screening—it is common among HIV-infected patients and requires systematic assessment 1
• Avoid using only current CD4 count for risk stratification—nadir CD4 count and time spent below specific thresholds also influence long-term outcomes 5, 2
• Do not delay cardiovascular risk assessment—multiple cardiac risk factors warrant aggressive management regardless of CD4 count 1