**6. Development of bioresources for HIV management**

**5.2. Antiretroviral prophylaxis**

10 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

In poor-resource settings, it is not uncommon to use antiviral therapy as a means of controlling the spread of infection. Experiments however showed that the administration of antiviral therapy, although it has a considerable control rate on HIV infection, is limited in its cost. Many HIV populations do not have access to ART [73] and to others are very expensive [74]. In Nigeria for instance the price of generic ART reported in 2001 could be over 10 times more expensive in comparison with Asian countries and about 79% lower in some European countries [75]. When antiviral therapy is considered as a chosen measure for HIV treatment, an additional use of these therapeutic agents serves as a preventive measure rather than a treatment option. The application of ART at a specific stage of disease progression (measured by computerised simulation incorporating CD4 count and HIV RNA level) has proved to be cost effective [76]. HIV prophylaxis treatment refers to the institution of measures taken to protect a person from HIV infection to which the individual has been anticipated or is liable to be exposed to HIV. HIV prophylaxis could either be post or pre-treatment option based. According to the US CDC, pre-exposure prophylaxis (PrEP) is designed for individuals who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking an antiretroviral drug every day [77]. Truvada which contains two HIV drugs (tenofovir and emtricitabine) is usually prescribed [78]. On exposure to HIV through sex or injection drug use, these drugs can work to keep the virus from establishing a permanent infection. PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92% when adhered to for at least 3 months [77]. Similarly, WHO describes post-exposure prophy‐ laxis (PEP) as contrasted by PrEP as a short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure, either occupationally or through sexual intercourse [79,80]. Post-exposure prophylaxis (PEP) involves taking a 28-day course of ARVs, for adults Tenofovir combined with either lamivudine (3TC) or emtricitabine (FTC) is prescri‐ bed. The recommended third drug by WHO is ritonavir-boosted lopinavir (LPV/r), which is also a preferred drug for HIV treatment. Zidovidune (AZT) and lamivudine (3TC) backbone drugs are used for children aged 10 or below, with ritonavir-boosted lopinavir (LPV/r) recommended as the third drug choice [81-84]. As effective as this preventive option may be, it faces challenges of adherences which has reduced its efficacy to less than 56%. Another challenge is the accessibility of the drug to individuals and accurate timing of exposure.

Limited studies on supply and distribution of antiviral drugs in poor-resource areas indicated that the mechanisms of supply and delivery of these drugs are not cost-effective [85-87]. The most significant concern is rural population having access to HIV antiviral drugs and the availability of laboratory facilities to monitor viral loads of patients on antiviral drug as response to therapy and for full HIV clinical management. One of the standard laboratory interventions used in the developed countries to monitor patients receiving antiviral drugs is the plasma viral load monitoring assay [88] which is not readily accessible to the wider

Contraceptives may simply be understood as devices or pills used to prevent unwanted pregnancies and diseases mostly sexually transmitted. These can be in the form of drugs,

population of HIV patients in resource-poor regions [89].

**5.3. Contraceptives**

Bioresources relate to the total biological variation manifested in individual plants, animals, or their genes, which could be utilized by humans for beneficial use such as drugs, food, livestock feed, etc. It also refers to the development of improved crops and animals for higher yield and tolerance to biotic and abiotic stresses. However, despite the global investment in bioresources and machinery to curb the spread of HIV, weak health systems and inadequate human resources are continuing to be major barriers to the elimination of the disease [5]. There is therefore need for an upgrade of the existing methods of disease control and prevention to include local biological resources such as herbs and other plant materials. Several biological organisms mostly plant species have been employed in preventing and managing HIV infection in developing or resource poor countries. Recently, this has metamorphosed into an institutional traditional medicine sector with growing patronage and herbal formulations. Though active antiretroviral therapy (ART) is the principal method for preventing immune deterioration, about 80% estimated Africans still use herbal remedies [97]. In addition, prophylaxis for specific opportunistic infections is indicated in particular cases. There has been increased use of local resources in the treatment of HIV/AIDS known as alternative or complementary therapy [98] with growing scientific journals that publish its procedure and outcome. Some herbal remedies have been found to inhibit one or more steps of HIV replication (Table 2). Though most herbal preparations treat HIV opportunistic infection [99], many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action. Since some plant substances are known to modulate several cellular factors, such as NF-kappa B and TNF-alpha, which are also involved in the replication of HIV. Their role as potential anti-HIV products should therefore be a desirable focus of attention. In conclusion, several plant-derived antiviral agents are good candidates for further studies, with a view to exploring their potentials and application in systemic therapy and/or prophylaxis of HIV infections and most probably in combination with other anti-HIV drugs. Plant resources in the form of herbal preparations provide cheaper and accessible antiretroviral therapy to the poor populations.


#### **6.1. Selected plant resources with anti-HIV activity**


**Table 2.** Selected plant resources with antiviral activity

modulate several cellular factors, such as NF-kappa B and TNF-alpha, which are also involved in the replication of HIV. Their role as potential anti-HIV products should therefore be a desirable focus of attention. In conclusion, several plant-derived antiviral agents are good candidates for further studies, with a view to exploring their potentials and application in systemic therapy and/or prophylaxis of HIV infections and most probably in combination with other anti-HIV drugs. Plant resources in the form of herbal preparations provide cheaper and

> Inhibition of HIV1/2 reverse transcriptase activity and integrase nuclear translocation through disrupting the interaction between

integrase and LEDGF/p75 [100]

Inhibit cell-to-cell transmission, viral replication and syncytia formation in HIV-

Phytochemicals Possibly as a protease inhibitor [101]

protease [102]

infected cells [106]

Inhibits HIV-1 reverse Transcriptase [108]

cellular fusion, and syncytium formation [109]

Replication [111]

Irreversible inhibition of HIV-1 integrase [112]

suberosol Anti-HIV replication activity [110]

Suksdorfin Suppresses HIV-1 viral

Inhibits reverse transcriptase,

Activity [107]

Croton tiglium Phorbol esters Inhibitory effects on HIV-1 proliferation and its

Mangosteen Mangostin and gamma-mangostin Inhibitory activity against HIV-1 protease [103]

Licorice Glycyrrhizin Inhibits HIV replication [104,105]

Biflavonoids, robustaflavone, and

accessible antiretroviral therapy to the poor populations.

12 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

**Plant Identified Compound Mechanism**

Wikstroelide M

D-tubocurarine and

(andrographolide)

Hinokiflavone

Acer okamotoanum Flavonoid gallate ester Anti-HIV-1 integrase

Michellamines A and B

Lanostane-type triterpene,

Dicaffeoylquinic acids: 3,5 dicaffeoylquinic acid, and 1 methoxyoxalyl-3,5-dicaffeoylquinic acid, Wedelolactone, a coumarin

Arctium lappa (Burdock) Orobol (an isoflavone derivative) Inhibits HIV-1 replication;

derivative;

**6.1. Selected plant resources with anti-HIV activity**

Andrographis paniculata Diterpene lactones:

Daphne acutiloba (Rehder

Dracontium peruviuanum

Rhus succedanea L. Garcinia

Ancistrocladaceae Ancistrocladus

multiflora

korupensis

Annonaceae Polyalthia suberosa

Apiaceae

Lomatium suksdorfii

Asteraceae Achyrocline satureioides (Lam.) DC (Marcela);

Thymelaeaceae)

(jergón sacha)
