Clinical Drug Experience Knowledgebase

EVALUATION OF THE EFFECT OF ARTEMISIA ANNUA AND MORINGA OLEIFERA ON IMMUNOLOGICAL RESPONSE IN HAART HIV PATIENTS at MRRH

HIV still remains a major public health burden in Uganda and Africa as a whole. It is estimated that about 36.9 million persons are infected worldwide with majority being in Africa. While most HIV persons in Uganda initiate HAART late sometimes with CD4 cell count below 350, making their immunological recovery very poor and putting them at higher risk of opportunistic infections, there are no established medicines for enhancement of immune responses.

Indeed a number of medicinal plants are reported to have anti-HIV effects and immune enhancement effect in vitro, however few to none have had their potential demonstrated in a controlled clinical study. This study will investigate A.annua supplemented with Moringa oleifera. Artemisia annua medicinal plant has been demonstrated to have immunological effects in laboratory studies as well as anti-HIV effects in vitro (Lubbe et al., 2012). Moringa oleifera has been reported to be used in up to 80% of HIV patients in Africa (Lubinga et al., 2012) and thus will be investigated as a nutritional supplement. Although there is improved access to testing and hence timely diagnosis for HIV with increased roll out of anti-retroviral therapy, many patients in resource limited settings still initiate HAART when the HIV-infection is in advanced stage. Initiation of HAART in patients with advanced HIV-infection has previously been associated with sub-optimal immunological recovery (Reda et al., 2012). In addition, in Uganda many HIV patients are reported to use herbal medicines in addition to HAART, including Aloe vera, Vernonia amygdalina and Moringa oleifera. (Lubinga et al., 2012). The challenge is that the clinical benefits of most of these herbal medicines remain unknown as well as their potential interactions with HAART. Artemisia annua powder which has been shown in vitro to have anti-HIV effects and in vivo to cause increase in monocytes and lymphocytes level (Lubbe et al., 2012; Ndhlala et al., 2016) is used by some HIV patients in Uganda claiming to improve their quality of life (Lubinga et al., 2012). However there are no data from controlled studies to prove these claims and thus enable adoption or rejection of Artemisia annua powder and Moringa oleifera as an adjunct to HIV treatment. Proof of beneficial effects of a given herbal remedy would provide an alternative to use of unproven herbal products as it is the case currently. Artemisia annua medicinal plant has been demonstrated to have immunological effects in laboratory studies as well as anti-HIV effects in vitro (Lubbe et al., 2012). Has a short plasma half-life. When given orally or rectally, dihydroartemisinin was safe and showed higher bioavailability in humans than artemisinin in an early pharmacokinetic study by Zhao et al (1993). The Cmax, Tmax, and T1/2 for orally delivered dihydroartemisinin were 0.13-0.71 mg/L, 1.33 h, approximately 1.6 h, respectively; for pure artemisinin they were 0.09 mg/L, 1.5 h, and 2.27 h, respectively. Alin et al (1996) compared orally delivered artemisinin and artemisinin-mefloquine combination therapy for treatment of P. falciparum malaria. Infected and uninfected patients had similar pharmacokinetic parameters. After a single dose, bioavailability of artemisinin was not altered. In the Ilet et al(2005) review of pharmacokinetic parameters of artemisinin and its derivatives, oral pure artemisinin doses ranged from about 6-11 mg kg/L in healthy subjects and Cmax was 0.15-0.39 mg/L. Dose seemed to have no major effect. An earlier study by Ashton et al (1998)compared increasing artemisinin doses of 250, 500, and 1000 mg per person and both Cmax and T1/2 showed dose-dependent increases of 0.21, 0.45, and 0.79 mg/L, and 1.38, 2.0, and 2.8 h, respectively, but Tmax remained relatively constant at 2.3-2.8 h. et al., (2011; 2012) has also found Artemisia tea at 2.5g dried leaves per adult infusion dose with 55-100mg artemisinin/L safe. Other pharmacokinetic studies have been duly added in the background section and show that artemisinin delivered by oral consumption of Artemisia annua dried leaves or encapsulated dried leaves of Artemisia Annua are generally safe (Weather et al., 2014; Elfawal et al., 2015; Desroslera and Weathers, 2016).

Moringa oleifera on the other hand has been reported to be used as a nutritional supplement and management of HIV infections in up to 80% of HIV patients in Africa (Monera et al., 2008; Lubinga et al., 2012; Popoola et al., 2013; Ndhlala et al., 2016; Roelofsen et al., 2017). Asare and colleagues (2012) also confirmed that intake of Moringa Oleifera is very safe at levels ≤ 1000 mg/kg b.wt. Monera and colleagues have also found out in a cross-over study that Co administration of Moringa oleifera Lam. leaf powder at the traditional dose did not alter the steady state pharmacokinetics of nevirapine in HIV infected adults (Monera Penduka et al., 2017).

A.3 OBJECTIVES List the major objectives/hypothesis, which have governed your choice of study design General objective

To determine the effect of Artemisia annua powder and Moringa oleifera on immunological and haematological response in patients on HAART.

Specific objectives

To determine effect of Artemisia annua in combination with Moringa oleifera on CD4 cell count in HIV patients on HAART.
To determine the effect of Artemisia annua with Moringa oleifera on viral load in patients on HAART.
To determine the effect of Artemisia annua with Moringa oleifera on full blood count and immunogloblins associated with HIV infections in HAART patients.
To determine the effect of Artemisia annua and Moringa oleifera on antiretroviral plasma drug level in patients on first line ART (UCG, 2016).
To determine the effect of Artemisia annua and Moringa oleifera on performance status and quality of life in HAART patients.
To profile any adverse effects of Artemisia annua and Moringa oleifera HIV patients on HAART.