Cardiovascular Disease Risk Factors in HIV-Infected Women After Initiation of Lopinavir/Ritonavir- and Nevirapine-Based Antiretroviral Therapy in Sub-Saharan Africa

Abstract

Background Limited comparative, prospective data exist regarding cardiovascular risk factors in HIV-infected women starting antiretroviral therapy (ART) in Africa. Methods In 7 African countries, 741 women with CD4<200 cells/mm3 were randomized to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n=370) or lopinavir/ritonavir (LPV/r, n=371). Lipids and blood pressure (BP) were evaluated at entry, 48, 96, and 144 weeks. Multivariable linear and logistic regression models were used to evaluate mean risk factor changes and clinically relevant risk factor changes. Results At entry, both NVP and LPV/r groups were similar regarding age (mean=33.5 [SD=7.1] yrs), CD4 (129 [67] cells/mm3), and HIV-1 RNA (5.1 [0.6] log10 copies/ml). Nearly all women had normal lipids and BP except for HDL. Over 144 weeks, the LPV/r compared to NVP group had significantly greater mean lipid increases (e.g. non-HDL: +29 vs. +13 mg/dL) and smaller HDL increases (+12 vs. +21 mg/dL). In contrast, the NVP compared to LPV/r group had greater mean increases in BP (e.g. diastolic BP: +5 vs. −0.5 mmHg). Significantly more women assigned LPV/r had week 144 “abnormal” lipid levels (e.g. HDL 29.7% vs. 14.8% and triglycerides 28.6% vs. 8.2%), and significantly more women assigned NVP had “abnormal” BP (e.g. diastolic BP 22.7% vs. 6.5%). Most differences remained significant when adjusted for baseline risk factor, age, CD4, and HIV-1 RNA. Conclusions In HIV-infected women initiating ART in Africa, LPV/r+TDF/FTC was associated with less favorable changes in lipids, and use of NVP+TDF/FTC was associated with less favorable changes in BP.

Short Communication: Lipids and Cardiovascular Risk After Switching HIV-1 Patients on Nevirapine and Emtricitabine/Tenofovir-DF to Rilpivirine/Emtricitabine/Tenofovir-DF

“…20 HIV-1 patients using nevirapine had a higher mean HDL-C compared to patients on efavirenz, boosted atazanavir or boosted lopinavir. [6][7][8] The association between nevirapine and higher HDL-C was also observed in our study. An increased production of apolipoprotein A1, HDL-C's major apolipoprotein, in patients using nevirapine could be a possible explanation.…”

“…8 Despite the study-limitations, the observed lipid and blood-pressure changes were highly significant. It is therefore unlikely that larger studies would find completely different results which would indicate that our observations occurred solely due to chance.…”

Hyperlipidaemia in HIV-Infected Patients on Lopinavir/Ritonavir Monotherapy in Resource-Limited Settings

“…We looked at the rate of hyperlipidemia solely among participants on LPV/r monotherapy while other studies looked at the rate of hyperlipidemia in participants on LPV/r-based HAART regimens of which some of the lipid elevations may have been due to NRTI use. [1, 21] The majority of individuals (73%) in the A5230 study were on an NVP-based regimen at the time of screening. [22] For first-line NNRTI based ART treatment, RLS treatment programs mainly rely on NRTI backbone of either zidovudine (AZT) or stavudine (d4T) and lamivudine (3TC) or, more recently, tenofovir (TDF)NRTIs are known to have a mild effect on lipids with a high degree of heterogeneity in lipid response.…”

“…In resource-rich countries, non-communicable diseases including cardiovascular disease (CVD) have become leading causes of morbidity and mortality in persons living with HIV/AIDS. Similarly, as HIV care and treatment becomes more widely available, CVD has become an emerging epidemic in resource-limited settings [1]. …”

Review of Cardiovascular Disease in HIV-Infected Women

“…Shaffer et al evaluated CHD risk factors following initiation of NNRTI vs. PI-based ART in women from 7 countries in sub-Saharan Africa over 144 weeks. ART with either nevirapine or lopinavir/ ritonavir had similar lipid values with only TC increasing at 144 weeks (p=0.090) [45]. However, Tien et al found no significant associations between ART and lipid values [46].…”