Background: The underlying mechanisms for the lipid disorders seen in HIV infected patients (pts) are not clear. A previous study showed reduced clearance rates of VLDL into denser lipoproteins in pts on antiretroviral therapy. We studied apolipoprotein B (Apo-B) kinetics in HIV^- control and three HIV⁺ pt groups.

Methods: We performed a cross sectional 9-hour tracer kinetic study with ¹³C-leucine. HIV pts were treatment naïve or taking triple antiviral medication containing protease Inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). CD4 counts were similar between the 3 HIV⁺ groups. VLDL Apo-B pool size, absolute secretion rate (ASR), and fractional clearance rate (FCR) were compared between the groups by Mann-Whitney test.

Results:

Table 1. Mean baseline fasting results

Patients (number)	Age (yrs)	BMI (Kg/m2)	Months on treatment	Total cholesterol (mmol/l)	Total triglyceride (mmol/l)
HIV negative-control (10)	47.0	25.4	0	5.0	1.3
NNRTI (10)	42.4	23.2	14.0	4.8	1.4
PI (8)	42.7	24.7	49.6	5.7	2.3
HIV positive-Control (12)	34.2	23.4	0	4.2	1.2

 

Table 2. Apo-B kinetics (mean ± SD)

	HIV negative	HIV positive-control	PI	NNRTI
VLDL Apo-B ASR (mg/kg/day)	9* ±1.5	33 ±16.8	32.3 ±17	36.4 ±25
FCR pools per day	12.3* ±6.1	12* ±5.9	6.3 ±3.6	6.2 ±3.5
VLDL Apo-B pool size (mg)	73* ±49	232 ±137	572 ±496	523 ±338

 

The VLDL Apo-B ASR was significantly lower* (p < 0.002) in the HIV negative group compared to the HIV positive groups. The FCR of treatment naïve and HIV negative groups were similar but both were significantly higher* (p < 0.04) than the treatment groups. There was no difference in the ASR and FCR between the 2 treatment groups. Compared to the HIV^- controls*, VLDL Apo-B pool size was larger in the HIV⁺ untreated (p = 0.002) and antiviral treated groups (p = 0.0001). Age, gender and time on treatment did not affect results.

Conclusions: HIV infection increases the absolute VLDL Apo-B secretion from the liver, while treatment with PI or NNRTI reduces its clearance from plasma, expanding the VLDL Apo-B pool size. This provides a possible mechanism for the increase in plasma triglyceride levels in HIV pts with further increase in the lipid levels after starting treatment with PI and NNRTI.