Skip to main content
Download PDF

Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial

AIDS Research and Therapy volume 21, Article number: 22 (2024) Cite this article

Abstract

Background

Initiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda.

Methods

282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months.

Results

At 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups.

Conclusion

A combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access.

Trial registration

ClinicalTrials.gov NCT03366922.

Introduction

AIDS, caused by HIV, is the most prevalent immunosuppressive disease and a significant global health challenge that continues to affect and take human lives [1, 2]. Globally, an estimated 39.0 million people were living with HIV at the end of 2022, two-thirds of whom are in the WHO African Region [3]. ART effectively controls HIV replication, increasing CD4 + T counts and decreasing mortality. However, 9–40% of PLWH fail to achieve CD4 T cell count normalization, often referred to as “inadequate immunological responders” with a CD4 T cell count threshold of < 350 cells/µl at 2 years after ART initiation [4]. Despite advancements in ART access, barriers like cost, geographic location, and healthcare infrastructure persist, particularly in resource-limited countries [5] causing physicians to initiate ART when infection is advanced leading to poor immunological recovery, putting them at a high risk of opportunistic infections [6]. PLWH commonly use herbal remedies to treat HIV, and opportunistic infections, and manage the side effects of ART [7,8,9]. The use of herbal medicines for HIV/AIDS management is a complex issue driven by various factors such as high costs, accessibility, and perceived benefits [9]. However, more clinical research is needed to explore the clinical impact of concurrent herbal use with antiretroviral therapy, assessing patient outcomes and potential harmful interactions [10].

In Uganda, PLWH frequently use herbal medicines such as Artemisia annua and Moringa oleifera before or in addition to ART [11], and some of them have been documented to have clinical benefits [12]. A. annua, also known as “African Wormwood” [13], has been shown to have immunological and anti-HIV effects, and its powder has been used by some HIV patients in Uganda [14, 15]. On the other hand, M. oleifera is a popular nutritional supplement for HIV-infected individuals [16], with up to 80% in Africa and Uganda consuming it as a main nutritional supplement. Moringa leaves are rich in proteins, vitamins, and antioxidants, that mutually work to improve the immunity and quality of life of HIV patients [17, 18]. Despite the growing interest in A. Annua and M. oleifera for their purported immunomodulatory and antiviral properties, there is a lack of comprehensive clinical evidence regarding their effects when supplemented to ART.

This study aimed to evaluate the immunologic effects and clinical benefits of combining A. annua and M. oleifera powders with ART in PLWH, with low CD4 count (≤ 350cells/µl), providing insights into potential adjunctive treatments for optimizing HIV management.

Methods

Study design and setting

The study was a double-blind, randomized controlled trial conducted at Mbarara Regional Referral Hospital’s (MRRH) HIV clinic in Uganda from December 2017 to August 2020. MRRH with 350 bed capacity is located in Mbarara City, Southwestern Uganda. Every day, the hospital receives 1,200-1,500 patients including 300 HIV-positive patients from different tribal and socio-demographic locations in Uganda. The hospital was chosen as a suitable site for this study because it provides care and services to HIV- positive patients and is equipped with trained staff, nurses, counselors, physicians, pharmacists, and lab technicians.

Recruitment of the study participants

The study involved HIV patients aged 18–66 years who had been on ART for at least one year. A Research assistant screened HIV-positive patients on ART at MRRH HIV Clinic, to identify those aged 18 years plus, with a CD4 count ≤ 350 cells/µl, living within 60 km from the clinic, having normal hematological, liver and renal function tests, and able to sign the informed consent. The study excluded pregnant women, those using other herbal or supplementary medicines, and those with pre-existing opportunistic infections. Research assistants obtained informed consent from all participants.

Randomization, blinding, and preparation of treatments for the study participants

Participants were first stratified according to baseline CD4 levels: 350–250, 249–150, and ≤ 149 before randomization to the three groups. Using computer-generated numbers supplied by an independent biostatistician, the block randomization method was used to assign eligible participants to one of the three study groups: ART alone as the control group (CG), ART with A. annua group (AG), or ART with A. annua + M. oleifera group (AMG) at a 1:1:1 ratio. The study involved two herbal treatments, A. annua and A. annua + M. oleifera, with participants and healthcare providers blinded to the specific treatment names. This was intended to avoid bias during the study. Both intervention herbal materials underwent quality tests before use by the participants.

Study procedures

Research assistants received opaque parcels already fixed with study codes. These parcels contained either 4 g of A. annua and 10 g of M. oleifera which were to be taken at least 8 h apart from each of the daily ARVs dosing. All participants were encouraged to take note and report all side effects.

Preparation of study materials

Leaf powders from Ugandan plants, A. annua and M. oleifera, were authenticated by a botanist and stored in a herbarium located at Mbarara University of Science and Technology (MUST). The study pharmacist prepared and packaged A. annua and M. oleifera leaf powders in 4 g and 10 g packets, respectively, adhering to good manufacturing practices.

Administration of treatments

Participants in the AG self-administered 4 g of A. annua leaf powder daily at 8 am, consumed in porridge or water, 8 h apart from their routine ARVs dosing, for 12 months. Participants in the AMG consumed 4 g of A. annua and 10 g of M. oleifera powders, mixed with porridge or water daily at 8 am, 8 h apart from their routine ARVs dosing, for 12 months. Participants in the control group received a placebo made by mixing cornstarch powder with food color, in addition to ART. Both the treatment herbs and the placebo were identically packaged and presented similarly.

Participants received one-month herbal treatments in parcels with study numbers, dosing instructions, and other safety information, including storage and safety details. Participants were reminded by an SMS to take their herbal medicine every morning between 7 and 8 am and were asked to respond with a message or call prompt. The study team collaborated with the HIV clinic to ensure that participants received regular HIV care, including ART, as prescribed. Participants were informed that herbal medicines are not replacements for ART in HIV treatment, and they were advised to continue taking prescribed ARVs as usual and correctly during the consenting process.

The study followed participants for 12 months and they were reviewed monthly by the study clinician.

Study measurements

Blood samples were collected post-enrollment but before initiation of herbal treatments, and six and twelve months after treatment initiation to measure CD4 count, viral load, complete blood count, and liver and renal enzymes. A blood sample was taken at 1- and 2-weeks post-treatment to evaluate ARV plasma levels.

Study outcomes

As our primary outcome, the study measured changes in absolute and relative CD4 counts after twelve months of follow-up, comparing intervention groups with control. Secondary outcomes included viral load changes, CBC, and antiretroviral plasma levels.

The study collected qualitative data on socio-demographics, herbal usage, depression, health [16], food insecurity [19], alcohol use [20], HIV stigma [21], and social support from study participants at enrolment.

Study sample size and statistical analysis

The mean CD4 count of HIV-positive patients aged 18+, taking ART, and maintaining a mean CD4 count of ≤ 350 cells/µl for over a year at MRRH was 160 ± 110. With that mean, a sample size of 282 participants—94 in each of the three arms—was required to detect a 30% rise in CD4 counts with 80% power at 0.05 alpha, assuming a 10% loss to follow-up.

All data were cross-checked for completeness before entry into STATA Version 12 for statistical analysis, using both intention-to-treat [22] and per-protocol methods. The chi-square test statistic was used to analyze categorical data while the Wilcoxon rank-sum (Mann-Whitney) test was used to compare means between the intervention groups and the control for both the primary and secondary outcomes. The per-protocol analysis analyzed participant follow-up time and compared mean changes in CD4 count over the same follow-up time of measurements. Linear regression analysis was used to determine the impact of demographic and anthropometric parameters on the primary outcome. In all analyses, statistical significance was considered at a p-value less than 0.05. The same analysis plan was used for secondary outcomes.

Ethical approval

The study was reviewed and approved by the MUST Research Ethics Committee (with reference number 27/05–17) and the Uganda National Council for Science and Technology (with reference number NCT03366922). The study adhered to the Helsinki Declaration’s ethical guidelines and kept all participant identities confidential, ensuring all informed consent was obtained from all participants. All treatments administered to participants have previously been documented to be safe when used for prophylaxis or as a supplement [14, 23].

Data safety and monitoring

The data and safety monitoring committee was constituted and included senior medical scientists to ensure the safety of participating individuals. Three safety checks were done at 1 month, at 50%, and 75% of recruitment.

Results

Participants flow

Out of the 1844 HIV-positive participants screened for eligibility at the MRRH HIV clinic in Southwestern Uganda, 319 were eligible. A total of 37(11.6%) declined participation in the study and 282 were randomized and enrolled to receive different treatments: The Artemisia plus Moringa group (AMG), the Artemisia group (AG), and the control group (CG). A total of 248 (87.9%) completed all study procedures, 26 (9.2%) participants were lost-to-follow-up, and 8 (2.8%) participants became pregnant and were discontinued from the study. Participants who successfully completed the study were included in the per-protocol analysis to cater for drop outs (Fig. 1).

Fig. 1
figure 1

Trial flow

Full size image

Demographic characteristics of the participants at enrolment

The average age was 40 years while the males dominated the three groups [CG = 49 (29.7%); AG = 56 (33.9%); AMG = 60 (36.4%)]. The majority had education above primary [CG = 68 (30%); AG = 78 (34.4%); AMG = 81(35.7%)], with irregular income, defined as consistent wages and monthly income [CG = 63 (28.1%); AG = 80 (35.7%); AMG = 81 (36.1%)]. The majority of the participants had no spouse [CG = 43 (28.3%); AG = 57 (37.5%) AMG = 52 (34.2%] with an average of 2 children per household. All the participants had similar demographic characteristics at baseline (Table 1).

Table 1 Baseline demographic and clinical characteristics of participants by group
Full size table

Anthropometric and immunological characteristics of the participants at enrolment

The study participants in the three groups displayed similar baseline anthropometric and immunological characteristics. The majority of the participants had a normal BMI of 19–24 kg/m2 [CG = 51 (29.8%); AG = 61 (35.7%); AMG = 59 (34.5%)]. The viral load (LVL) of the majority of the patients was high [CG = 6.0 (± 2.1); AG = 6.2 (± 2.4); AMG = 6.0 (± 2.2)], with the CD4 count below < 350 cells/µl [CG = 221.8 (± 88.9); AG = 214.7 (± 86.6); AMG = 227.5(75.7)] yet they had been on ART for at least 53 months [CG = 62.2 (± 41.1); AG = 166.1 (± 1021.3); AMG = 53.4 (36.7)] before the study. The baseline haematological characteristics of the participants were the same, with efavirenz and nevirapine common to all ART regimens (Table 1).

Effect of interventional treatments on the primary and secondary outcomes

In terms of outcomes, we noted a statistically significant difference when comparing CD4 counts at baseline with those at month 12 for each intervention group. After 12 months of patient follow-up, administration of A. annua + M. oleifera produced a significant absolute mean CD4 increment of 105.06 ± 7.25 cells/µl, (p < 0.001). Equally, administration of A. annua alone produced a lower absolute mean CD4 increment of 60.84 ± 7.20 cells/µl, (p = 0.001) compared to the control group (Table 2).

Table 2 Effect of A. annua, and A. annua + M. oleifera on CD4 count
Full size table

Furthermore, we calculated the relative difference in CD4 count. At 12 months of patient follow-up, the administration of A. annua + M. oleifera produced a relative mean CD4 increment of 30.45 ± 6.14 cells/µl (p < 0.001), while the administration of A. annua alone produced a relative mean CD4 increment of 26.04 ± 6.12 cells/µl (p = 0.001) compared to the control group. There was no statistically significant difference in the absolute and relative CD4 counts at 6 months in both the intervention groups compared to the control group (Table 2). Additionally, our data shows that patients who were assigned to the AMG group showed greater platelet levels (p = 0.025) and White Blood Cell counts (p = 0.003) than those who were assigned to the CG (Table 3).

Table 3 Effect of A. annua, and A. annua + M. oleifera on secondary outcomes after 12 months of treatment
Full size table

Our findings further indicate that there was a higher proportion of participants achieving a viral load of less than 50 copies/ml in the AMG 67 (77.9%), and AG 61 (69.3%) compared to the control group (p = 0.038) (Table 3), while there was no significant difference in the efavirenz and nevirapine plasma levels among the participants in the intervention treatments. Whereas we did not observe a difference in the results of liver and kidney function tests and reported side effects across all the groups (results not shown), we recorded one death in the control group 5 months into the study.

Effect of demographic, immunological, and anthropometric factors absolute CD4 count

The linear regression analysis conducted on HIV-positive patients treated with ART alone and those additionally treated with M. oleifera and A. annua revealed significant differences in absolute CD4 count. Patients in the AMG had a predicted increase of 44.22 cells/mm³ in absolute CD4 count compared to those in CG (ART only). Conversely, patients in the CG had a predicted decrease of 60.84 cells/mm³ in absolute CD4 count compared to the baseline. Furthermore, none of the demographic (age, p = 0.102; gender, p = 0.869 and income, p = 0.388) and anthropometric (BMI, p = 0.451) characteristics explored was observed to significantly influence absolute CD4 count over the study period (Table 4).

Table 4 Linear regression analysis of demographic, immunological, and anthropometric factors influencing absolute CD4 count
Full size table

Discussion

After 12 months of patient follow-up, we observed significant differences in CD4 counts between the intervention and control groups. When compared to the AG and the CG, the AMG exhibited a significant absolute mean CD4 increment. Conversely, while the AG’s absolute mean CD4 increase was smaller than that of the AMG, it was still significantly higher than that of the CG (Table 2). The difference in CD4 counts across the intervention groups implies that, in comparison to A. annua alone or conventional care, the combined use of A. annua and M. oleifera may have had a synergistic impact in increasing immunological response. This outcome may arise from the possible changes in the biological effects and/or bioavailability of individual phytochemicals upon combination. Many combinations of pure bioactive compounds or plant extracts, each rich in phytochemicals, have been shown in numerous studies to exhibit synergistic effects [24, 25]. These combinations can result in enhanced biological activities, such as improved antioxidant properties, anti-inflammatory effects, and increased efficacy in combating various health conditions [26, 27]. This is a very useful finding because these two plants can be used as adjuvants to ART to improve health outcomes among PLWH since the plants can be cultivated in people’s homes. Both these plants have previously been documented to be safe when used for prophylaxis or as a supplement [23], and so this combination may provide a readily available and affordable source of supplement that can improve suppression of HIV replication and enabling CD4 regain to restore the body’s ability to fight against opportunistic infections [5].

Although the interventions increased CD4 count, this increase was gradual and only reached statistical significance in month 12, implying that the impact of the interventions on immune reconstitution takes time to manifest, which offers insights into the immune response in the individuals receiving A. annua and M. oleifera alongside ART. This discovery is especially significant because CD4, whose depletion is a hallmark of HIV infection, is a critical indicator of the health and efficiency of the immune system. The results also imply that the combined intervention may increase immunity over the long run, because plant-based medicine has the characteristics of slow onset [28], potentially providing a more all-encompassing strategy for HIV management by actively promoting immunological responses in addition to inhibiting viral replication with ART.

It should also be noted that, as one of the inclusion criteria, this study investigated HIV-positive individuals who had been on ART for at least a year but had a CD4 count below 350 cells/µl. Studies show that individuals who initiate ART with a CD4 count < 350 cells/µl often struggle to achieve CD4 counts > 500 cells/µl after up to 10 years on ART [29], and this might explain the slow immunological recovery.

HIV clinicians have long relied on CD4 as a disease progression predictor [30], but recent guidelines recommend viral load testing as the preferred monitoring strategy for clinical response to ART [31]. After a year of follow-up, participants in the AG and the AMG showed a statistically significant reduction in their viral load when compared to those receiving standard care. This is a promising and clinically relevant finding in the context of managing HIV infection. Reducing viral load is a major treatment objective in the management of HIV/AIDS since it is a crucial indicator of the quantity of HIV in the blood. Given that the viral load of both intervention groups significantly decreased, it is possible that using M. oleifera—alone or in conjunction with A. annua —has antiviral properties. This finding can be collaborated by a study done by [32], who concluded that leaf infusion of M. oleifera has, among other things, antivirus properties. In addition, M. oleifera is rich in bioactive substances that have been shown to have positive effects on health [33, 34]. As such, A. annua may be complementing it to potentially enhance the immune response [35] and contribute to viral suppression.

We further observed that treating HIV patients with A. annua and M. oleifera alongside ART did not affect their efavirenz and nevirapine plasma levels. This is an important finding regarding the safety and effectiveness of concurrent herbal medicine use in HIV-positive patients who receive these antiretroviral medications for the management of HIV. For these medications to be effective in inhibiting viral replication and halting the emergence of drug-resistant viruses, their plasma levels must remain unchanged. This lack of interaction is worth noting because it implies that the co-administration of A. annua and M. oleifera does not disrupt the pharmacokinetics of these antiretroviral drugs and hence affects their efficacy. These findings are supported by observations from previous studies that demonstrated no statistically or clinically significant interaction following 14 days of nevirapine and Moringa co-administration [16].

We also investigated the effect of demographic and anthropometric factors on the primary outcome (absolute CD4 counts) over the treatment period in the CG and the AMG (Table 4). The study found no evidence of a significant relationship between the absolute CD4 count, age, income, BMI, or gender. This suggests that the CD4 levels in this patient population may not be directly impacted by these factors. At enrollment, the majority of the participants (69%) were within the normal BMI range of (19–24 kg/m2) while only 3% had a BMI > 30 kg/m2. Our results agree with a study carried out by Cianflone et al. in which they concluded that BMI > 30 kg/m2 was not beneficial in the ART era and was associated with smaller CD4 count increases [36]. Additionally, our study is in agreement with that of Bahemana et al. who found no difference in long-term CD4 recovery by age at ART initiation [37].

Finally, as a secondary outcome, participants in the AMG achieved a statically significant increase in the platelet count compared to the those in the AM and CG. Changes in platelet count might have therapeutic implications, particularly in patients with HIV infection who may be at risk of thrombocytopenia. Platelets are essential for immunological response and hemostasis.

Our study had several strengths. The study successfully maintained blinding to treatment allocation, despite the bitterness of A. Annua, by combining porridge with the interventions during dozing. The study utilized dried plant powders, prepared by an independent pharmacist, and consumed at least 8 h apart from routine ART dosing to prevent interaction. We studied A. annua and M. oleifera which offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access.

Despite the strengths pointed out, our study had some important limitations. The control arm experienced a higher dropout rate due to challenges like transportation and food insecurity, which were not adequately addressed through SMS reminders. Further, we did not maintain objective measures of ART adherence or evaluate food intakes using methods like dietary records or 24-hour recall. The ARV interaction study had limitations, including a short period for potential interactions with herbs and food supplements, potentially reducing concentrations.

Finally, we recruited relatively healthy PLWH, and therefore our results may not be generalizable for individuals with renal, and liver function problems, existing opportunistic infections, or pregnant.

Conclusion and recommendation

The study found that daily consumption of M. oleifera and A. annua leaf powders improves CD4 count, viral load suppression, and platelet count among PLWH on ART, without affecting efavirenz and nevirapine plasma levels. The findings from this study provides valuable insights into the potential benefits of M. oleifera and A. annua supplementation in HIV-positive patients on ART as adjuvant therapy. We recommend further research to rigorously measure and evaluate ART adherence by the participants. Further research is needed to determine the long-term impact of M. oleifera-A. annua combination on CD4 count, viral load, liver and kidney enzymes, and ARV plasma levels. The authors also recommend further studies of these interventions on wound healing and reduction of opportunistic infections among PLWH on ART.

Data availability

The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.

Abbreviations

AIDS:

Acquired immune deficiency syndrome

AMAMED:

Action for Natural Medicine in the Tropics

AMG:

Artemisia + Moringa group

ART:

Antiretroviral therapy

AG:

Artemisia group

BMI:

Body mass index

CD4:

Cluster de differentiation 4

CG:

Control group

CI:

Confidence interval

HIV:

Human immunodeficiency virus

MRRH:

Mbarara Regional Referral Hospital

MUST:

Mbarara university of science and technology

PLWH:

People living with HIV

SD:

Standard deviation

References

  1. Vithalani J, Herreros-Villanueva, M %J A health sciences. HIV Epidemiology in Uganda: survey based on age, gender, number of sexual partners and frequency of testing. Afr Health Sci. 2018;18:523–30.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tian X, Chen J, Wang X, Xie Y, Zhang X, Han D, Fu H, Yin W, Wu N. Global, regional, and national HIV/AIDS disease burden levels and trends in 1990–2019: a systematic analysis for the global burden of disease 2019 study. Front Public Heal. 2023;11:1068664.

    Article  Google Scholar 

  3. Global HIV. (2021) AIDS statistics—2020 fact sheet; 2020.

  4. Fan L, Li P, Yu A, Liu D, Wang Z, Wu Y, Zhang D, Zou M, Ma P. (2023) Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients. Front Med 10.

  5. Gunda DW, Kilonzo SB, Kamugisha E, Rauya EZ, Mpondo BC, %J. (2017) Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study. B M C Res notes 10:1–6.

  6. Reda AA, Biadgilign S. Determinants of adherence to antiretroviral therapy among HIV-infected patients in Africa. AIDS Res Treat. 2012. https://0-doi-org.brum.beds.ac.uk/10.1155/2012/574656.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Prasad S, Tyagi AK, %J F. function (2015) Curcumin and its analogues: a potential natural compound against HIV infection and AIDS. 6:3412–3419.

  8. Basri NF, Ramli AS, Mohamad M, Kamaruddin KN, %J BMCCM, Therapies. Traditional and complementary medicine (TCM) usage and its association with Patient Assessment of Chronic Illness Care (PACIC) among individuals with metabolic syndrome in primary care. BMC Complement Med Ther. 2022;22:1–15.

    Article  Google Scholar 

  9. Shiferaw A, Baye AM, Amogne W, Feyissa M. (2020) Herbal medicine use and determinant factors among HIV/AIDS patients on antiretroviral therapy in tikur anbessa specialized hospital, Addis Ababa, Ethiopia. HIV/AIDS-Research Palliat Care 941–949.

  10. Mbali H, Sithole JJK, Nyondo-Mipando AL. Prevalence and correlates of herbal medicine use among anti-retroviral therapy (ART) clients at Queen Elizabeth Central Hospital (QECH), Blantyre Malawi: a cross-sectional study. Malawi Med J. 2021;33:153–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lubinga SJ, Kintu A, Atuhaire J, Asiimwe S, %J. Concomitant herbal medicine and antiretroviral therapy (ART) use among HIV patients in Western Uganda: a cross-sectional analysis of magnitude and patterns of use, associated factors and impact on ART adherence. AIDS Care. 2012;24:1375–83.

    Article  CAS  PubMed  Google Scholar 

  12. Helfer M, Koppensteiner H, Schneider M, Rebensburg S, Forcisi S, Müller C, Schmitt-Kopplin P, Schindler M, Brack-Werner R. The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor. PLoS ONE. 2014;9:e87487.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Taxis K, Li S-M, Heide L. Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of artemisinin Annua L.(Annua Wormwood). Am J Trop Med Hyg. 2004;70:128–32.

    Article  PubMed  Google Scholar 

  14. Lubbe A, Seibert I, Klimkait T, van der Kooy F. Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia annua. J Ethnopharmacol. 2012;141:854–9.

    Article  PubMed  Google Scholar 

  15. Ogwang PE, Ogwal JO, Kasasa S, Ejobi F, Kabasa D, Obua C. (2011) Use of Artemisia annua L. infusion for malaria prevention: mode of action and benefits in a Ugandan community. Br J Pharm Res. https://0-doi-org.brum.beds.ac.uk/http://hdl.handle.net/10570/332.

  16. Monera-Penduka TG, Maponga CC, Wolfe AR, Wiesner L, Morse GD, Nhachi CFB, %J. Effect of Moringa oleifera Lam. Leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study. AIDS Res Ther. 2017;14:1–7.

    Article  Google Scholar 

  17. Deshmukh P, Sharma RK, Sharma V, Jain P. Immunomodulatory activity of Moringa oleifera in albino rats. J Anim Res. 2015;5:277–81.

    Article  Google Scholar 

  18. Asare GA, Gyan B, Bugyei K, Adjei S, Mahama R, Addo P, Otu-Nyarko L, Wiredu EK, Nyarko A. Toxicity potentials of the nutraceutical Moringa oleifera at supra-supplementation levels. J Ethnopharmacol. 2012;139:265–72.

    Article  PubMed  Google Scholar 

  19. Tsai AC, Bangsberg DR, Frongillo EA, Hunt PW, Muzoora C, Martin JN, Weiser SD. Food insecurity, depression and the modifying role of social support among people living with HIV/AIDS in rural Uganda. Soc Sci Med. 2012. https://0-doi-org.brum.beds.ac.uk/10.1016/j.socscimed.2012.02.033.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA, (ACQUIP ACQIP. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Arch Intern Med. 1998;158:1789–95.

    Article  CAS  PubMed  Google Scholar 

  21. Cloete A, Simbayi LC, Kalichman SC, Mthembu PP, Mkhonta RN, Ginindza T. Measuring AIDS stigmas in people living with HIV/AIDS: the internalized AIDS-related stigma scale. AIDS Care. 2009. https://0-doi-org.brum.beds.ac.uk/10.1080/09540120802032627.

    Article  PubMed  Google Scholar 

  22. Lesaffre E. (2008) Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis 66.

  23. Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, García-Muñoz B, González-Grande R, Pizarro A, Durán JA. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–21.

    Article  PubMed  Google Scholar 

  24. Wilson EMP, Sereti I, %J I. reviews (2013) Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs. Sec Clin Nutr 254:343–354.

  25. Ayaz M, Ullah F, Sadiq A, Ullah F, Ovais M, Ahmed J, Devkota HP. Synergistic interactions of phytochemicals with antimicrobial agents: potential strategy to counteract drug resistance. Chem Biol Interact. 2019;308:294–303.

    Article  CAS  PubMed  Google Scholar 

  26. Phan MAT, Paterson J, Bucknall M, Arcot J. Interactions between phytochemicals from fruits and vegetables: effects on bioactivities and bioavailability. Crit Rev Food Sci Nutr. 2018;58:1310–29.

    Article  CAS  PubMed  Google Scholar 

  27. Pezzani R, Salehi B, Vitalini S, Iriti M, Zuñiga FA, Sharifi-Rad J, Martorell M, Martins N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: an update on the cancer perspective. Med (B Aires). 2019;55:110.

    Google Scholar 

  28. Jiménez-Osorio AS, Jaen-Vega S, Fernández-Martínez E, Ortíz-Rodríguez MA, Martínez-Salazar MF, Jiménez-Sánchez RC, Flores-Chávez OR, Ramírez-Moreno E, Arias-Rico J, Arteaga-García F. Antiretroviral therapy-induced dysregulation of gene expression and lipid metabolism in HIV + patients: beneficial role of antioxidant phytochemicals. Int J Mol Sci. 2022;23:5592.

    Article  PubMed  PubMed Central  Google Scholar 

  29. OARAC. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. J Org Chem. 2021;86:693–708.

    Google Scholar 

  30. Moorhouse M, Conradie F, Venter F. What is the role of CD4 count in a large public health antiretroviral programme? South Afr J HIV Med. 2016;17:1–3.

    Article  Google Scholar 

  31. Lecher SL, Fonjungo P, Ellenberger D, Toure CA, Alemnji G, Bowen N, Basiye F, Beukes A, Carmona S, de Klerk M. HIV viral load monitoring among patients receiving antiretroviral therapy—eight Sub-saharan Africa Countries, 2013–2018. Morb Mortal Wkly Rep. 2021;70:775.

    Article  CAS  Google Scholar 

  32. Rahayu I, Timotius KH. Phytochemical Analysis, Antimutagenic and antiviral activity of Moringa oleifera L. Leaf Infusion Stud. 2022;27:4017.

    CAS  Google Scholar 

  33. Islam Z, Islam SM, Hossen F, Mahtab-ul-Islam K, Hasan MR, Karim R. Moringa oleifera is a prominent source of nutrients with potential health benefits. Int J Food Sci. 2021. https://0-doi-org.brum.beds.ac.uk/10.1155/2021/6627265.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Su X, Lu G, Ye L, Shi R, Zhu M, Yu X, Li Z, Jia X, Feng L. Moringa oleifera Lam.: a comprehensive review on active components, health benefits and application. RSC Adv. 2023;13:24353–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Xiao X, Wang J, Meng C, Liang W, Wang T, Zhou B, Wang Y, Luo X, Gao L, Zhang L. Moringa oleifera Lam and its therapeutic effects in immune disorders. Front Pharmacol. 2020;11:566783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Crum-Cianflone NF, Roediger M, Eberly LE, Vyas K, Landrum ML, Ganesan A, Weintrob AC, Barthel RV, Agan BK, Group IDCRPHIVW. Obesity among HIV-infected persons: impact of weight on CD4 cell count. Aids. 2010;24:1069–72.

    Article  PubMed  Google Scholar 

  37. Bahemana E, Esber A, Dear N, Ganesan K, Parikh A, Reed D, Maganga L, Khamadi S, Mizinduko M, Lwilla A. Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African cohort study. AIDS Res Ther. 2020;17:1–8.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the data collection team and the Director of the MRRH Immune Suppression Syndrome Clinic. We are also very grateful to the volunteers who participated in this study.

Funding

This study was funded by ANAMED INTERNATIONAL in partnership with Pharmbiotechnology and Traditional Medicine African Center of Excellence. The funders, however, did not have any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda

    Silvano S. Twinomujuni, Esther C Atukunda, Musinguzi Nicholas & Patrick E. Ogwang

  2. Department of Pharmacology and Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda

    Jackson K. Mukonzo

  3. Action for Natural Medicine in the Tropics (ANAMED INTERNATIONAL), Winnenden, Germany

    Felicitas Roelofsen

Authors
  1. Silvano S. Twinomujuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esther C Atukunda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jackson K. Mukonzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Musinguzi Nicholas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Felicitas Roelofsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrick E. Ogwang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

STS, analyzed the data and drafted the manuscript. ECA, OPE, and FR designed the study and reviewed the manuscript. JKM conducted the HPLC analysis of the drug levels. All authors read and approved the final manuscript. MN analyzed the data.

Corresponding author

Correspondence to Silvano S. Twinomujuni.

Ethics declarations

Consent for publication

Participants’ consent was obtained for the study and publication of these data.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Twinomujuni, S.S., Atukunda, E.C., Mukonzo, J.K. et al. Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial. AIDS Res Ther 21, 22 (2024). https://0-doi-org.brum.beds.ac.uk/10.1186/s12981-024-00609-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/s12981-024-00609-4

Keywords

AIDS Research and Therapy

ISSN: 1742-6405

Contact us