Background:  Co-morbidity in HIV-1 infection are often attributed to medications used to treat the disease. However, many of these co-morbidities appear to be multifactorial.

Methods:  A retrospective, longitudinal analysis of over 7000 patients in the HIV Outpatient Study (HOPS) cohort was performed to evaluate the host, disease, and treatment factors associated with several co-morbidities. Case control and multivariate logistic regression models were utilized.

Results:  Although there was some overlap with associated factors, the co-morbidities studied clustered into 2 groups based on an analysis of non-drug factors. The first group was associated primarily with nadir CD4 T-lymphocyte count < 200 cells/mm³:  lipoatrophy (OR = 2.62, p = 0.008), peripheral neuropathy (OR = 1.50, p < 0.001), anemia (OR = 2.44, p < 0.001), cardiomyopathy/pulmonary hypertension (OR = 3.51, p = 0.006), renal insufficiency (Clcr < 70 cc/min) (OR = 4.35, p <0.001), and liver dysfunction (> X3 ULN) (OR = 1.67, p < 0.001); or nadir CD4 T-lymphocyte count < 100 cells/mm³; pancreatitis (OR = 2.02, p = 0.007). The second group of factors was associated with higher viral loads:  rash associated with nevirapine (OR = 1.91, p < 0.001), rash associated with efavirenz (OR = 1.42, p = 0.006), rash associated with abacavir (OR = 2.83, p < 0.001), and hypogonadism (OR = 1.67, p = 0.010). Direct drug-associated co-morbidities included avascular necrosis (corticosteroids:  [OR = 5.35, p =0.011]) and (indinavir [OR = 10.6, p = 0.010]) and nephrolithiasis (indinavir [OR = 6.08, p < 0.001]). Although specific drugs were associated with all of the co-morbidities, the associated non-drug factors appeared to augment the likelihood of these co-morbidities as did standard doses of drugs in individuals weighing less than 68 kg.

Conclusions:  Some HIV-1 co-morbidities and toxicities are more prevalent in those individuals with more advanced disease. Nucleoside-associated toxicities are more likely to be seen with lower nadir CD4 counts. Drug associated rashes and some endocrinologic disorders are more commonly seen in patients with higher viral loads. Consideration should be given to both earlier initiation of treatment of HIV-1 infection and dose adjustments of ART based on weight.

Keywords: Antiretroviral Toxicities; Co-morbidities; Nadir CD4 count