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Medicine » Infectious Diseases » "Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure", book edited by Ibeh Bartholomew Okechukwu, ISBN 978-953-51-2157-2, Published: September 2, 2015 under CC BY 3.0 license. © The Author(s).

Chapter 1

Spatiotemporal Dynamics of HIV Distribution Pattern and Application of Indigenous Bioresources and Microbicides in Expanding Preventive Options

By Habu Josiah Bitrus and Ibeh Bartholomew Okechukwu
DOI: 10.5772/61000

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Spatiotemporal Dynamics of HIV Distribution Pattern and Application of Indigenous Bioresources and Microbicides in Expanding Preventive Options

Habu Josiah Bitrus1 and Ibeh Bartholomew Okechukwu2

1. Introduction

HIV infection has maintained a high number of infections in human population. Currently, there are growing population changes and corresponding challenges including new recombinant circulating forms. The infection is endemic in sub-Saharan Africa with peculiarities in the distribution pattern.

Similarly, distinct transmission models have emanated over the years thus forming a special focal point in the management and prevention of HIV/AIDS. In resource poor settings, management of the disease remains a task as financial, infrastructure, and committed human resources are remarkably low. The current treatment options though widely accepted is still marred with issues of accessibility, resistance, toxicity, and financial burden on the recipient patients. This chapter discusses and brings to concept the current HIV distribution pattern and microbial bioresources deployed as a preventive and treatment option.

2. Global HIV population distribution pattern with emphasis on Africa

The global population of the virus infection has maintained an alarming rate, with record values of more than 34 million people currently living with HIV [1,2] compared to less than 30 million observed in 2002 [3]. The geographical spread of the disease has been astronomical in sub-Saharan Africa, with Nigeria having an estimated amount of 8% of the total global burden of the infection [4].

The distribution and spread of the infection globally is entirely non-uniform and non-homogenous, with more concentrated cases (over 70%) of occurrence observed in Africa alone [5] (Figure 1A/1B and Figure 2). This estimate is extremely significant, given the fact that Africa accommodates approximately 15.3% of the world population [6]. As previously observed in the global spread of the disease, correlation between disease prevalence and social behaviours such as sexual practices and use of intravenous drugs are existential. The spread of infection in Africa is more pronounced and is relative to cultural practices. For example, HIV population is seen to be least prevalent in the northern African countries and the Middle East (Figure 2), which are typically known to practice less of cultural deeds that predispose individuals to HIV infection. Conversely, the spread is dramatically highest in the southern region of the continent [3] where HIV infection appears to have been densely concentrated amongst injection drug users, gays, sex workers, partners of sex workers, etc. [7]. Not only is the prevalence of the disease highest in Africa per global scale, but the rate of rise of occurrence has also been astronomical on the continent, with estimated seven-fold increase in the number of occurrences between 2005 and 2012 [4].


Data presented in Figures 1A and 1B are based on 2014 ECDC report [8], 2014 UN women report [9], and 2014 UNAIDS Gap report [10]

Figure 1.

(A) Regional HIV Population distribution pattern expressed as relative percentage based on 2013 data. (B): Regional HIV Population distribution based on 2013 data.

3. Transmission dynamics models

3.1. Routes of transmission, geographical and racial distribution

In sub-Saharan Africa, the major route of transmission is through heterosexual contact rather than homosexual interaction. In an endemic country like Cameroon, for example, whereas at 2012, the HIV prevalent rate amongst adults was 4.3% (4.0%–4.6%), the infection is concentrated within the 15–49 age bracket in which over 50% of the infected population are women [11]. The major mode of transmission identified by UNAIDS is largely heterosexual, with high occurrence amongst groups such as commercial sex workers, long distance truck drivers, injection drug users, and gay partners [12] with more than half of new HIV infection occurring through heterosexual activity [13]. The transmission of HIV infection is geographic as well as racial (as exemplified by cultural and social values) dependent (Figure 2). Differing factors has been adduced for infection rates in Africans, Asians, Americans, and Europeans which includes social values [14], economic stability/poverty [15, 16], level of awareness [17], and host genetic factors [18].

The three main established routes of transmission of the infection are sexual contact [19], blood transmission [20], needle sharing [21], and vertical (mother-to-child) [22] transmission. Heterosexual transmission seems to be the most common means of infection in Africa with over 60% of the global HIV infections [23] in contrast to other regions of the world, such as in USA which has homosexual transmission and needle sharing as the dominant means [19] (Figure 3). Sharing needles and injection instruments is thought to be three times more likely to transmit HIV than sexual intercourse.

The increased burden of HIV prevalence amongst women in endemic regions have been opined to be due to certain reproductive tract/biological susceptibility [24], social, physical, economical, and even psychological factors which women especially in sub-Saharan Africa are subjected to [25,26].


Figure 2.

Estimated number of people (all ages) living with HIV based on 2013 WHO data

Available data shows that men who have sex with men (MSM) remain the group with the highest prevalence of HIV infection in the USA, accounting for up to 78% of total infection, as observed amongst men [27] (Figure 3). The prevalent rates amongst MSM are also recorded to increase in the order, Hispanic MSM (6,700), black MSM (10,600), and white MSC being the highest (11,200) [27]. Up to 16% of total HIV reported cases are due to intravenous drug users (IDUs) in which they represent 8% of new cases [28]. Similarly, Europe has a high number of HIV occurrences from MSM [29]. It could be observed that in high income countries HIV epidemics is highly associated with MEM sexual networks [30, 31,32] while heterosexual contacts prevail in low income regions [33,34,35] (Figure 3).


The data shows the prevalence based on 2013 United Nations Office on Drugs and Crime data from the annual report questionnaire and national Government reports, 2013 UNAIDS report and CDC publications. Note: IDUs stands for injecting drug users.

Figure 3.

Regional distribution of HIV routes of transmission in HIV positive population

3.2. Exploring transmission models

Since both heterosexual and homosexual behaviour is a potent factor for increased HIV transmission rate, exploring the dynamics of this mode perhaps could be a sure way of providing and discovering a lasting HIV treatment option and drug design. A number of HIV epidemic models have emerged, particularly the modes of transmission (MOT) model recommended by the Joint United Nations Programme on HIV/AIDS (UNAIDS) [36,37]. The MOT model as developed in 2002 aims to identify persons at risk of HIV infection [38] with subsequent prevention policies and programmes [39]. This model was recommended for country-wide studies in the year 2008 as part of a synthesis process supported by UNAIDS and the World Bank Global HIV/AIDS Monitoring and Evaluation Team [40], with emphasis on local content and immediate environment prevailing circumstances. The MOT model utilizes accurate information on recent prevalence of HIV infections in a given population and the assumed patterns of risk behaviour within different risk groups (MSM, prostitutes, etc.) to calculate the expected distribution of new adult HIV infections the next year in terms of the mode of exposure. Certain considerations are necessary for a comprehensive and adequate utilization of this model either at country or community level studies. These considerations as noted by WHO are the proportion of the adult male and female population that belongs to each of several risk groups identified, such as commercial sex workers and their patronizers, injection drug users, men who sex men (MSM), persons of multiple heterosexual sex partners, the low risk group such as partners of persons with higher-risk behaviour and married or cohabiting couples with one monogamous heterosexual partner in the last year [41]. The model tends to resolve issues such as complexity in risk groups, for example, a prostitute who is a drug injection user. Secondly, the prevalent rate of HIV infection and of a generic sexually transmitted disease (STI) identified in each risk group [41]. Thirdly, the average numbers of sexual or injecting partners and exposures per partner with considerations of personal level protective behaviour (such as condom use or the use of new needles), for individuals in each risk group and lastly the probability of HIV transmission per exposure act in each risk group, taking into account the effect of STIs and the prevalence of male circumcision [41].

4. Recombinant circulating forms and distribution pattern

The capacity of HIV to exhibit a unique high genetic variability has posed a major challenge to its treatment [42]. The genetic diversity is also attributed to a high error rate of the HIV genome during transcriptase reaction and also high genetic recombination rate [43].

Recombination is defined as the process whereby various subtypes or strains of the HIV shuffle their genomic characteristics to form an entirely new strain. This recombination tactic, a system of alteration of the HIV genetic constitution, is mostly common with the HIV subtype-1 (HIV-1) and it is commonly called new circulating recombinant forms (CRFs) (Table 1). There also exists the HIV subtype-2 (HIV-2), which is relatively less pathogenic in comparison to HIV-1 [44]. The occurrence of CRF is closely linked to the dynamism of the HIV infection and epidemic and obviously to failure of most specific therapeutic target in eliminating the virus [45-47]. The study of the distribution pattern of the various subtypes is therefore highly crucial for effective HIV management especially in endemic regions of the world. Recombination occurs at a very rapid rate estimated to be in the order of 2.8 cross-over per genome per cycle [48]. Recombination events between subtypes lead not only to an ever increasing diversity of the HIV strains [49] but also presents astonishing scenarios of emerging strains with resistance to the common antiviral drugs [50,51]. The numbers of CRFs are increasing astronomically global, partly because of the emergence of recombinants of the various subtypes in various local epidemiological regions [46]. There has also been a correlation between the emergence of divergent subtypes in a population and the teeming occurrence of disease cases. For example, in Cameroon, the number of newly infected individuals increased from 8,596 to 10,625 between 2006 and 2007 as the number of recombinant subtypes increases in the studied population [47]. Criteria set to define a new subtype, sub-subtype, or CRF include having the representative strain identified in at least three individuals who have no direct epidemiological relationship. Three full-length genomic sequences are required but two complete genomes together with partial sequences of a third strain could also define a new subtype, sub-subtype, or CRF. CRFs are derived from recombination between viruses of different subtypes which are each given a number. CRF12_BF, for example, is a recombination between subtypes B and F.

IM: Major (90%) A(A1,A2A3) CRF19_CPX,CRF01_AE,CFR14_BG,CRF03_AB,31_BC,CFR06/18_CPXWest Africa ,Cuba[52,53,54]
BCRF07/8_BC,CRF15/48/51/52/53/54/55/58/59_01BEurope, Japan, Thailand, Australia, the Americas [55]
CCRF10/41_CD, CRF11/45/49/37/36_CPXS/E Africa, India, Nepal, China [55]
DCRF05_DF,CRF13_CPX, CRF16_A2D,CRF19_CPXEastern and Central Africa [55]
ECRF01_AE* Africa [55]
F (F1 F2)CRF12_BF1,CRF22_01A1,CRF25_CPX,CRF26_AUCentral Africa, S. America, Eastern Europe [56]
GCRF02_AG,CRF09/56/65_CPX,CRF20/23/24_BGAfrica and Central Europe [56]
HCRF32_06A1,CRF33/34_01B,CRF35_AD,CRF38/39/40/42/44/46/47/70/71/72_BF,CRF43_02GCentral Africa [56]
ICRF04_CPXOnly in central America [57]
North, Central and W. Africa Caribbean [56]
KCRF04/06/18/27_CPX,CRF21_A2DCongo DR and Cameroon [56]
IIN:Non- M,Non-O
O:OutlierCameroon [58]
P:PendingWest-Central Africa, Cameroon [59]
BW. Africa, Angola, Mozambique, India, Brazil[60]
C-HWest Africa [61,62]
Liberia, Sierra Leone, Ivory Coast [61,62]

Table 1.

HIV Classification and global CRFs

[i] - * Recombine only with A, G, H, K, U, CPX=complex recombination of several subtypes (ADG)

5. HIV/AIDS prevention strategies, how well have they worked?

There are three major strategies of HIV prevention, namely, education or knowledge base, contraceptives, and antiretroviral treatment.

5.1. Peer education

Amongst the many ways of curbing the onslaught of the HIV, one of the most vital is educating the populace about the disease and its transmission dynamics. This significantly prevents re-infection and protects those who are not already infected [63, 64, 65]. Therefore, inadequate knowledge of the disease transmission equals resultant failure of all the measures originally put together to tackle the spread of the disease. In a research conducted in 2006 to access the effect of prior knowledge of HIV transmission relative to the number of occurrence of the infection in Boston, USA, it was found that a significant proportion of the infected people are those with significantly little or no knowledge of the disease or its mode of transmission [66]. Increase in HIV education, particularly amongst young people, remains the most effective way of tackling the HIV onslaught. Where this form of education is limited, the disease is known to prevail [67, 68] as also noted from various data in sub-Saharan Africa. Education on HIV/AIDS plays a major role in controlling the spread of the disease amongst young people, which consequently determines the global spread of infection. HIV infection has been captured as the second most prevalent killer amongst young people. As of 2012, one-third of the global new HIV infection was discovered to be amongst young people, with total infection of about 780,000 and concentrated within 15–24 age group [69]. This number has obviously dropped down from 2012 to present due to vigorous and continuous education campaigns but, even so, HIV/AIDS deaths amongst the young people worldwide are still at an alarming rate [70, 71]. Proper education enables young people and married adults to better protect themselves against the sexually transmitted route of HIV infection, vertical transmission, and also behaviours such as intravenous drug use [72]. So significant was the global implication of HIV/AIDS infection on young people that it was opined that HIV education should be dispensed even to healthy ones.

5.2. Antiretroviral prophylaxis

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

5.3. Contraceptives

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, hormones, or devices such as condoms and intrauterine devices (IUD). Evidently, hormonal contraceptives and pills do not protect against HIV or other sexually transmitted infections (STI). At present there are no contraceptives, with the exception of condoms (male and female), that protect against HIV infection [90]. Since the only forms of birth control that will protect against HIV are abstaining from vaginal (and anal) sex or using condoms while having sex, WHO therefore recommends dual protection technique for unwanted pregnancy and HIV prevention [91]. Birth control options that do not protect against HIV infection include oral contraceptives, birth control shot (injection of the hormone Depot Medroxyprogesterone Acetate (DMPA) in the arm to release progestin)/Depo-provera, morning after pill (Levonorgestrel or Ulipristal acetate) used after sexual activity, implants (implanon/norplant), IUDs which release progestin, female condoms such as diaphragm/vagina ring/sponge/cervical cap, withdrawal and spermicides. Currently, a new intravaginal ring that helps prevent pregnancy while simultaneously releasing low doses of an antiretroviral drug that reduces a woman’s risk of contracting both HIV and genital herpes has been designed [92,93]. This device releases doses of the contraceptive Levonorgestrel and the antiretroviral HIV medication tenofovir after being inserted in the vagina for 90 days and has demonstrated a 39% protection against HIV infection in women [93]. It is obvious that many contraceptive pills may not be compatible with ARTs, the widely prescribed antiretroviral drug efavirenz substantially reduces levels of the hormonal contraceptive Levonorgestrel [94] and increases the risk of HIV infection [95,96].

6. Development of bioresources for HIV management

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

Plant Identified Compound Mechanism
Daphne acutiloba (Rehder Thymelaeaceae)Wikstroelide MInhibition of HIV1/2 reverse transcriptase activity and integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75 [100]
Dracontium peruviuanum
(jergón sacha)
D-tubocurarine and PhytochemicalsPossibly as a protease inhibitor [101]
Croton tigliumPhorbol estersInhibitory effects on HIV-1 proliferation and its protease [102]
MangosteenMangostin and gamma-mangostinInhibitory activity against HIV-1 protease [103]
LicoriceGlycyrrhizinInhibits HIV replication [104,105]
Andrographis paniculataDiterpene lactones: (andrographolide)Inhibit cell-to-cell transmission, viral
replication and syncytia formation in HIV-infected cells [106]
Acer okamotoanumFlavonoid gallate esterAnti-HIV-1 integrase
Activity [107]
Rhus succedanea L. Garcinia multifloraBiflavonoids, robustaflavone, and HinokiflavoneInhibits HIV-1 reverse
Transcriptase [108]
Ancistrocladaceae Ancistrocladus korupensisMichellamines A and BInhibits reverse transcriptase,
cellular fusion, and
syncytium formation [109]
Polyalthia suberosa
Lanostane-type triterpene, suberosolAnti-HIV replication activity [110]
Lomatium suksdorfii
SuksdorfinSuppresses HIV-1 viral
Replication [111]
Asteraceae Achyrocline satureioides (Lam.)
DC (Marcela);
Dicaffeoylquinic acids: 3,5-
dicaffeoylquinic acid, and 1-
methoxyoxalyl-3,5-dicaffeoylquinic acid, Wedelolactone, a coumarin derivative;
Irreversible inhibition of
HIV-1 integrase [112]
Arctium lappa (Burdock)Orobol (an isoflavone derivative)Inhibits HIV-1 replication;
blocks cell-to-cell
transmission of HIV-1 [113]
Combretum molle R.Br. ex G.Don
GallotanninInhibits HIV-1 reverse
transcriptase [114]
Terminalia chebula, Euphorbia pekinensisGallic acid and galloyl glucoseInhibits HIV reverse
transcriptase and integrase [115]

Table 2.

Selected plant resources with antiviral activity

6.2. Challenges of HIV Bioresources Development and Bioprospecting in Developing Nations

Several challenges face development of bioresources effective in enhancing antiretroviral development in low and mid-income countries. Such problems are mostly institutional highlighted as follows:

  1. Lack of appropriate framework for deployment and exchange of bioresources materials within and amongst countries

  2. Weak genetic banking infrastructure

  3. Absence of advanced analytical and simulation laboratories

  4. Weak linkage of existing bioresources centres to local industries

  5. Absence of effective communication channel to supposed end users/beneficiaries of the eventual product

  6. Weak standardization and evaluation procedure for products emanating from bioresources

  7. Absence of a bioprospecting policy

7. Microbicides as preventive/treatment options

Microbicides are applications applied inside the vagina or rectum that protects against sexually transmitted infections (STIs) including HIV. These types of chemical applications could be formulated as gels, creams, films, or suppositories. Microbicides are potential HIV prevention options which can reduce the spread of HIV especially among women in developing countries. Without a preventive HIV vaccine, microbicides [116] offer an alternative to condoms as the most feasible method for primary prevention of HIV. Microbicides- intravaginal/intrarectal topical formulations of anti-HIV agents have also been proposed to prevent HIV transmission. Currently, antiretroviral-based microbicides have been achieved for the prevention of HIV new infections among women after many years of failed trial. More than 60 candidate agents have been identified to have in vitro activity against HIV, several of which have advanced to clinical testing stage.

At least 10 reverse transcriptase inhibitors and 16 entry inhibitors have been or are in the process of being investigated in clinical or preclinical trials. Ideally, these compounds are characterized by high potency, low absorption from the vagina to the blood to minimize development of resistance, and have a long half-life in order to remain active over a long period. Tenofovir has also been formulated as a topical vaginally applied gel and assessed for its protective effect against Simian immunodeficiency virus (SIV) in macaques. The results indicated that the macaques receiving the tenofovir gel were completely protected from infection [117] and in human trials [118]. The results of the human trial were released in July 2010 and showed that use of the gel reduced acquisition of HIV infection by 39% overall, and by 54% in women who were highly adherent to gel use [118].

Topical microbicides are grouped into five classes of agents, based on their mode and site of action [119] (Table 3)

Microbicides type Mechanism Formulation and year Countries of clinical trial
Surfactants/membrane disruptors-based microbicidesVirucidal action through disrupting the viral envelope1.Nonoxynol-9 (N9) 1985 [120]
2. C31G(cetylbetaine and myristamine oxide)1997 [121]
3. Sodium lauryl sulphate (Invisible Condom)2002 [122]
Kenya, Cameroon
Vaginal milieu protector based microbicides Enhance the natural protective mechanisms within the vaginal canal through altered pH rangeBufferGel, PRO 2000 Gel [123]Malawi; South Africa; Hlabisa, South Africa; Zambia; Zimbabwe; USA
Microbicide based on inhibition of HIV entry in the host cell Negative charge, anionic polymers interact with HIV's viral envelope proteins and interfere with the attachment and fusion of HIV to target cellCMPD167, Maraviroc (MVC), cyanovirin-N, Cellulose sulphate, SPL7013.2010 [124,125]USA, Kenya
Benin, India, Uganda, South Africa
Microbicides that act after entry of HIV in the host cells Prevention of replication and release through inhibition of the virus-encoded reverse transcriptase (RT) or integrase (IN)Tenofovir 2010 [126-128] South Africa, Uganda, Zimbabwe
Microbicides based on inhibitors with unknown mechanism of action Combination of extracts prepared from plants with anti-retroviral properties of unknown mechanismPraneem 2005 [129] BasantIndia

Table 3.

Microbicides and their mechanism of action

For development of acceptable microbicide, researchers must develop not only the active ingredient but also a socially acceptable, affordable, and easy to apply microbicide providing protection for several days and/or weeks. Other major issues include how a microbicide might affect sperm and the possibility of causing adverse effects in women reproductive health. In Table 3 the listed microbicides failed to achieve the desired results except for tenofovir gel which showed 39% less likelihood for users to become infected with HIV than women who received a placebo gel. For women who adhered to tenofovir gel prescription correctly, HIV infection was 54% less likely than the placebo group.

8. Conclusion

HIV is widely distributed globally. Strong effort and interpersonal encouragement should be channeled on exploring and developing bioresources with antiretroviral potential to serve as a springboard for cheaper and locally available HIV drugs in addition to developing appropriate bioprospecting policies. Behavioural change and abstinence remain a sure means of HIV prevention, but need to be complemented with additional biomedical options especially in the populations most vulnerable to HIV infection.


1 - Joint United Nations Programme on HIV and AIDS, UNAIDS report 20 2012.
2 - UNAIDS. Global Fact Sheet, Joint United Nations Programme on HIV and AIDS, 2010.
3 - UNAIDS Report on the Global AIDS Epidemic 2010.
4 - UNAIDS 2012 report. (accessed December 2014).
5 - United Nations, World populations. (accessed September 2014).
6 - Samuels F, Wagle S. Population mobility and HIV and AIDS: review of laws, policies and treaties between Bangladesh, Nepal and India. London: Overseas Development Institute, 2011.
7 - European Centre for Disease Prevention and Control/WHO Regional Office for Europe. HIV/AIDS surveillance in Europe 2013. Stockholm: European Centre for Disease Prevention and Control, 2014.
8 - UN Women Fact Sheet: Promoting the Legal Empowerment of Women in the Context of HIV/AIDS. 2014. (accessed 20 February 2015).
9 - UNAIDS. The Gap Report, 2014. 20 February 2015).
10 - Rapport National De Suivi De La Declaration Politique Sur Le Vih/Sida Cameroun. Global AIDS Response Progress (GARP), 2014. (accessed 22 February 2015).
11 - Gouws E, White PJ, Stover J, Brown T. Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples. Sex Transm Infect 2006; 82(iii): 51–55.
12 - CDC. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data – United States and 6 U.S. dependent areas – 2012. HIV Surveillance Supplemental Report 2014; 19(No. 3).
13 - UNAIDS. FINAL SYMPOSIUM REPORT on Social norms and collective behaviour: How education needs to transform to better contribute to HIV prevention, treatment, care and support. ED/UNP/HIV/IATT/REPORT/2010/3.UNAIDS Inter‐Agency Task Team on Education, May, 2010.
14 - Dinkelman T, Lam D, Leibbrandt M. Linking poverty and income shocks to risky sexual behaviour: evidence from a panel study of young adults in cape town. The South African Journal of Economics 2008; 76(supp1): s52–s74.
15 - Durevall D, Lindsko A. Economic Inequality and HIV in Malawi. Department of Economics School of Business, Economics and Law at University of Gothenburg Vasagatan 1, PO Box 640, SE 405 30 Göteborg, Sweden.
16 - Chirwa E, Malata A, Norr K. HIV prevention awareness and practices among married couples in Malawi. Malawi Medical Journal: The Journal of Medical Association of Malawi 2011; 23(2): 32–37.
17 - Chatterjee K. Host genetic factors in susceptibility to HIV-1 infection and progression to AIDS. Journal of Genetics 2010; 89(1): 109–116.
18 - Boily MC, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infectious Disease 2009; 9(2): 118–129.
19 - Kleinman SH, Lelie N, Busch MP. Infectivity of human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion. Transfusion 2009; 492454.
20 - Kaplan EH, Heimer R. A model-based estimate of HIV infectivity via needle sharing. Journal of Acquired Immune Deficiency Syndrome 1992; 5(11): 1116–1118.
21 - Ioannidis JP, Abrams EJ, Ammann A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. <1000 copies/ml. The Journal of Infectious Diseases. 2001; 184(4): 539–545.
22 - Joint United Nations Programme on HIV and AIDS, UNAIDS report 2011; 20–30.
23 - Rodriguez-Garcia M, Barr FD, Crist SG, Fahey JV, Wira CR. Phenotype and susceptibility to HIV infection of CD4 Th17 cells in the human female reproductive tract. Mucosal Immunology 2014; 7: 61375.
24 - Caldwell B, Pieris I, Ichuda B, Caldwell J. Sexually regimes and sexual networking: the risk of an HIV/AIDS epidemic in Bangladesh. Social Science and Medicine 1999;48: 1103–1116.
25 - Higgins JA, Hoffman S, Dworkin SL. Rethinking gender, heterosexual men, and women’s vulnerability to HIV/AIDS: time to shift the paradigm. American Journal of Public Health 2010; 100(3): 435–445.
26 - CDC. Estimated HIV incidence among adults and adolescents in the United States, 2007–2010. HIV Surveillance Supplemental Report 2012; 17(No. 4).
27 - CDC. 1981. Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men—New York City and California. MMWR Morbidity and Mortality Weekly Report 1981; 30: 305–308.
28 - Lucy P, Emma J, Vivian H, Alisher, Ford H, Lucy R, Tim R. HIV in the European region: vulnerability and response. World Bank, Washington, DC. © World Bank 2013. License: CC BY-NC-ND 3.0 IGO
29 - van Griensven F, van Wijngaarden JWDL, Baral S, Grulich A. The global epidemic of HIV infection among men who have sex with men. Current Opinion in HIV and AIDS 2009; 4(4): 300–307.
30 - Beyrer C. Global prevention of HIV infection for neglected populations: men who have sex with men. Clinical Infectious Diseases 2010; 50(supplement 3): S108–S113.
31 - Likatavicius G, van de Laar M. HIV and AIDS in the European Union, 2011, Eurosurveillance 2011; 17(48): Article ID 20329, 2012.
32 - Beyrer C, Baral SD, Walker D, Wirtz AL, Johns B, Sifakis F. The expanding epidemics of HIV type 1 among men who have sex with men in low-and middle-income countries: diversity and consistency. Epidemiologic Reviews 2010; 32(10): 137–151.
33 - McIntyre JA. The need for HIV prevention interventions for men who have sex with men in Africa. Sexually Transmitted Infections 2010; 869(20): 82–83.
34 - Baral S, Sifakis F, Cleghorn F, Beyrer C. Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000–2006: a systematic review. PLoS Medicine 2007; 4(12): article e339.
35 - Gouws E, White PJ, Stover J, Brown T. Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples. Sexually Transmitted Infectections 2006; 82(iii): 51–55. doi: 10.1136/sti.2006.020164
36 - Joint United Nations Programme on HIV/AIDS & The World Bank Global HIV/AIDS Program. Zambia HIV prevention response and modes of transmission analysis. Lusaka; 2009.
37 - Pisani E, Garnett GP, Grassly NC, Brown T, Stover J, Hankins C, et al. Back to basics in HIV prevention: focus on exposure. BMJ 2003; 326: 1384–1387.
38 - Brown T, Peerapatanapokin W. The Asian epidemic model: a process model for exploring HIV policy and programme alternatives in Asia. Sexually Transmitted Infections 2004; 80(i): 19–24.
39 - Colvin M, Gorgens-Albino M, Kasedde S. Analysis of HIV prevention response and modes of HIV transmission: the UNAIDS-GAMET-supported synthesis process. Johannesburg: UNAIDS Regional Support Team Eastern and Southern Africa; 2008. (accessed 27 November 2014).
40 - Case KK, Ghys PD, Gouws E, Eaton JW, Borquez A, Stover J, Cuchi PP, Abu-Raddad JL, Garnett GP, Hallett TB. The HIV modelling consortium: understanding the modes of transmission model of new HIV infection and its use in prevention planning. Bulletin of the World Health Organization 2012; 90: 831–838A.
41 - Robertson DL, Hahn BH, Sharp PM. Recombination in AIDS viruses. Journal of Molecular Evolution 1995; 40(3): 249–259.
42 - Martin DP, Williamson C, Posada D. Rdp2: recombination detection and analysis from sequence alignments. Bioinformatics 2005, 21(2): 260–262.
43 - Kannangai R, David S, Sridharan G. Human immunodeficiency virus type 2-A milder, kinder virus: an update. Indian Journal of Medical Microbiology 2012; 30(1): 6–15.
44 - Vijay NNV, Vasantika, Ajmani R, Perelson AS, Dixit NM. Recombination increases human immunodeficiency virus fitness, but not necessarily diversity. Journal of General Virology 2008; 89(6): 1467–1477.
45 - Kotaki1 T, Khairunisa SQ,Witaningrum AM,Yunifiar MQ, Sukartiningrum SD, Diansyah MN, Rahayu1 RP. Nasronudin13 and Masanori Kameoka HIV-1 transmitted drug resistance mutations among antiretroviral therapy – Naïve individuals in Surabaya, Indonesia. AIDS Research and Therapy 2015, 12: 5.
46 - Sampathkumar R, Shadabi E, Luo M. Interplay between HIV-1 and host genetic variation: a snapshot into its impact on AIDS and therapy response. Advances in Virology 2012; 2012: Article ID 508967, 16 pages. doi:10.1155/2012/508967.
47 - Zhuang J, Jetzt AE, Sun G, Yu H, Klarmann G, Ron Y, Preston BD, Dougherty JP. Human immunodeficiency virus type 1 recombination: rate, fidelity, and putative hot spots. Journal of Virology 2002; 76: 11273–11282.
48 - Konings FA, Haman GR, Xue Y, Urbanski MM, Hertzmark K, Nanfack A, Achkar JM, Burda ST, Nyambi PN. Genetic analysis of HIV-1 strains in rural eastern Cameroon indicates the evolution of second-generation recombinants to circulating recombinant forms. Journal of Acquired Immune Deficiency Syndrome 2006; 42: 331–341.
49 - Moutouh L, Corbeil J, Richman DD. Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure. Proceedings of the National Academy of Sciences USA 1996; 93: 6106–6111.
50 - Ragupathy V, Zhao1 J, Wood O, Tang S, Lee S, Nyambi P, Hewlett I. Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon. Virology Journal 2011; 8: 185.
51 - Zhang M, Foley B, Schultz A, Macke JP, Bulla I, Stanke M, Morgenstern B, Korber B, Leitner T. The role of recombination in the emergence of a complex and dynamic HIV epidemic. Retrovirology 2010, 7: 25.
52 - Mbanya D, Sama M, Tchounwou P. Current status of HIV/AIDS in Cameroon: how effective are control strategies? International Journal of Environmental Research and Public Health 2008; 5(5): 378–383.
53 - Bobkov AF, Kazennova EV, Selimova LM et al. Temporal trends in the HIV-1 epidemic in Russia: predominance of subtype A. Journal of Medical Virology 2004; 74(2): 191–196.
54 - Robertson DL, Hahn BH, Sharp PM, Hahn, Goudsmit S, Jaap. Viral sex; the nature of AIDS. Oxford University Press. New York, 1997, 51–58.
55 - Buonaguro L,Tonesello ML,bvuonaguro FM.Human immunodeficiency virus type 1subtype distribution in the worldwide epidermic:Patogenic and Therapeutic implications.Journal of virology 2007,81,19:10209-10219.
56 - Kouri V,Khouri R, Alemán, Y, Abrahantes Y, Vercauteren J, Pineda-Peña A, Theys K, Megens S, Moutschen M, Pfeifer N, Van eyenbergh J,. Pérez AB, Pérez J, Pérez L, Van Laethem K, Vandamme A., CRF19_cpx is an Evolutionary fit HIV-1 variant strongly associated with rapid progression to AIDS in Cuba. EBioMedicine 2015; 2(3): 188–189.
57 - Yamaguchi J, Coffey R, Vallari A, Ngansop C, Mbanya D, Ndembi N, Kaptué L, Lutz G. Gürtler, Bodelle P, Schochetman G, Devare SG, Brennan CA. Identification of HIV Type 1 Group N infections in a husband and wife in Cameroon: viral genome sequences provide evidence for horizontal transmission. AIDS Research and Human Retroviruses 2006; 22(1): 83–92.
58 - Peeters M, Gueye A, Mboup S, Bibollet-Ruche F, Ekaza E, Mulanga C, Ouedrago R, Gandji R, Mpele P, Dibanga G, Koumare B, Saidou M, Esu-Williams E, Lombart JP, Badombena W, Luo N, Vanden Haesevelde M, Delaporte E.Geographical distribution of HIV-1 group O viruses in Africa. AIDS 1997; 11(4): 493–498.
59 - Plantier JC, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, Lemée V, Damond F, Robertson DL, Simon F. A new human immunodeficiency virus derived from gorillas. Nature Medicine 2009; 15(8): 871–872.
60 - Santiago ML, Range F, Keele BF, Li Y, Bailes E, Bibollet-Ruche F, Fruteau C, Noë R, Peeters M, Brookfield JFY., Shaw GM, Sharp PM, Hahn BH. Simian Immunodeficiency virus infection in free-ranging sooty Mangabeys (Cercocebus atys atys) from the Taï Forest, Côte d'Ivoire: implications for the origin of epidemic human immunodeficiency virus Type 2. Journal of Virology 2005; 79(19): 12515–12527.
61 - Marx PA, Alcabes PG, Drucker E. Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa. Philosophical Transactions of the Royal Society B; Biological Sciences 2001; 356(1410): 911–920.
62 - Medley A, Kennedy C, O’Reilly K, Sweat M. Effectiveness of peer education interventions for HIV prevention in developing countries: a systematic review and meta-analysis. AIDS Education and Prevention 2009; 21(3): 181–206.
63 - UNAIDS. Peer education and HIV/AIDS: concepts, uses and challenges. (accessed 2 December 2014).
64 - Tolli MV. Effectiveness of peer education interventions for HIV prevention, adolescent pregnancy prevention and sexual health promotion for young people: a systematic review of European studies. Health Education Research 2012; 27(5): 904–913.
65 - Smith Fawzi MC, Jagannathan P, Cabral J, Banares R, Salazar J, Farmer P, Behforouz H. Limitations in knowledge of HIV transmission among HIV-positive patients accessing case management services in a resource-poor setting. AIDS Care 2006; 18(7): 764–771.
66 - UNESCO report. Education for all by 2015, will we make it: regional overview of sub Saharan Africa. (accessed 25 February 2015).
67 - Baxen J, Breidlid A. Researching HIV/AIDS and education in Sub-Saharan Africa: examining the gaps and challenges. Journal of Education 2004; 34: 9–29.
68 - WHO. Health for the world’s adolescents: a second chance in the second decade. 2014.
69 - Suzuki PTC, Gillespie A, Kasedde S, Idele P. Disparities and trends in AIDS mortality among adolescents living with HIV in low- and middle-income countries. 20th International AIDS Conference, Melbourne, abstract MOAC0101, July 2014.
70 - Idele P, Gillespie A, Porth T, Suzuki C, Mahy M, Kasedde S, Luo C. Epidemiology of HIV and AIDS among adolescents: current status, inequities, and data gaps. Journal of Acquired Immune Deficiency Syndrome 2014; 66: S144–S153.
71 - Paul-Ebhohimhen VA, et al. a systematic review of school-based sexual health interventions to prevent STI/HIV in sub-Saharan Africa. BMC Public Health 2008; 8: 4.
72 - WHO Library Cataloguing-in-Publication Data Access to antiretroviral drugs in low- and middle-income countries: technical report July 2014. (accessed 16 January 2015).
73 - Ford N, Ananworanich J, Ruxrungtham K, Simmons B, Hill A. Is the pricing of antiretrovirals equitable? Analysis of antiretroviral drug prices in 20 low- and middle-income countries. 7th IAS Conference on HIV Pathogenesis Treatment and Prevention, 30 June–3 July 2013, Kuala Lumpur, Malaysia. Oral abstract 2013.
74 - Coalition of Civil Society Groups on Access to Essential Medicines. A price comparison of selected HIV/AIDS drugs in Nigeria. Reports and Studies. Journalist against AIDS publication 2001.
75 - Goldie SJ, Yazdanpanah Y, Losina E, Weinstein MC, Anglaret X, Walensky RP, Hsu HE, Kimmel A, Holmes C, Kaplan JE, Freedberg KAN. Cost-effectiveness of HIV treatment in resource-poor settings – the case of Côte d'Ivoire. England Journal of Medicine 2006; 14; 355(11): 1141–1153.
76 - CDC. Pre-exposure prophylaxis (PrEP). (accessed August 2014).
77 - CDC. Preexposure prophylaxis for the prevention of HIV infection in the United States – 2014 a clinical practice guideline. 1–67.
78 - WHO. Supplementary section to the 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, Chapter 5 – Clinical guidelines across the continuum of care: HIV diagnosis and ARV drugs for HIV prevention.
79 - WHO. Guidelines on post-exposure prophylaxis for HIV and the use of co-trimoxazole prophylaxis for HIV-related infections among adults, adolescents and children. Recommendations for a public health approach – December 2014 supplement to the 2013 consolidated ARV guidelines.
80 - Agaba PA, Agaba EI, Ocheke AN, Daniyam CA, Akanbi MO, Okeke EN. Awareness and knowledge of human immunodeficiency virus post exposure prophylaxis among Nigerian Family Physicians. Nigerian Medical Journal: Journal of the Nigeria Medical Association 2012; 53(3): 155–160.
81 - Rutland E, Sundaram S, Mani R. The awareness of postexposure prophylaxis for HIV infection following sexual exposure in emergency departments in a regional HIV network. International journal of STD & AIDS 2010; 21(9): 636–637.
82 - Anon. Guidelines on Post Exposure Prophylaxis for HIV. Recommendations for a Public Health Approach. World Health Organization, Geneva, 2014.
83 - WHO. Post-exposure prophylaxis to prevent HIV infection Factsheet 2014. (accessed 29 December 2014).
84 - Schouten EJ, Jahn A, Ben-Smith A, et al. Antiretroviral drug supply challenges in the era of scaling up ART in Malawi. Journal of the International AIDS Society 2011; 14(Suppl 1): S4.
85 - Chandani Y, Felling B, Allers C, Alt D, Noguera M, Zuber A. Supply chain management of anitretroviral drugs: considerations for initiating and expanding national supply chains. DELIVER, for the U.S. Agency for International Development, Arlington, 2006.
86 - Waning B, Diedrichsen E, Moon S. A lifeline to treatment: the role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries. Journal of the International AIDS Society. 2010; 13: 35.
87 - Hammer SM, Schechter M, Montaner JS, et al. International AIDS Society-USA panel. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 2006; 296: 827–843.
88 - Badri M, Lawn SD, Wood R. Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting. BMC Infectious Diseases 2008; 8: 89.
89 - UNAIDS/WHO. HIV and hormonal contraception Frequently asked questions. 2012.
90 - Philips GMSJ, Baggaley RC, Steyn P, Temmerman M. HIV and contraception – complex issues for safe choice: the latest recommendations from the World Health Organization (WHO). 20th International AIDS Conference, Melbourne, abstract THAC0505LB, 2014.
91 - Clark JT, Clark MR, Shelke NB, Johnson TJ, Smith EM, Andreasen AK, Nebeker JS, Fabian J, Friend DR, Kiser PF. Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy. PLoS One 2014; 9(3): e88509.
92 - Johnson TJ, Clark MR, Albright TH, Nebeker JS, Tuitupou AL, Clark JT, Fabian J, McCabe RT, Chandra N, Doncel GF, Friend DR, Kiser PF. A 90-day Tenofovir reservoir intravaginal ring for mucosal HIV prophylaxis. Antimicrobial Agents and Chemotherapy 2012; 56(12): 6272–6283.
93 - Scarsi K et al. Efavirenz, but not nevirapine antiretroviral therapy, decreases exposure tolevonorgestrel released from a sub-dermal contraceptive implant. Journal of the International AIDS Society 2014; 17(3): 4, abstract 0131.
94 - Chen MCP, Kwok C, Bernholc A, Low N. For the HC-HIV IPD meta-analysis study group hormonal contraception and HIV infection: results from a large individual participant data meta-analysis. 20th International AIDS Conference, Melbourne, abstract THAC0503, 2014.
95 - Kilembe WKW, Naw HK, Brill I, Vwalika B, Chomba E, Johnson B, Haddad L, Tichacek A, Allen S. Weighing 17 years of evidence: does hormonal contraception increase HIV acquisition risk among Zambian women in discordant couples? 20th International AIDS Conference, Melbourne, abstract THAC0504, 2014.
96 - WHO, author. Traditional medicine strategy 2002–2005. World Health Organisation, Geneva, 2002.
97 - King R, Homsy J. Involving traditional healers in AIDS education and counselling in sub-Saharan Africa: a review. AIDS 1997; 11(Suppl A): S217–S225.
98 - Langlois-Klassen D, Kipp W, Jhangri GS, Rubaale T. Use of traditional herbal medicine by AIDS patients in Kabarole District, Western Uganda. The American Journal of Tropical Medicine and Hygiene 2007; 77(4): 757–763.
99 - Zhang X, Huang SZ, Gu WG, Yang LM, Chen H, Zheng CB, Zhao YX, Wan DC, Zheng YT. Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation. Chinese Journal of Natural Medicines 2014; 12(3): 186–193.
100 - Napolitano A, et al. Qualitative on-line profiling of ceramides and cerebrosides by high performance liquid chromatography coupled with electrospray ionization ion trap tandem mass spectrometry: the case of Dracontium loretense. Journal of Pharmaceutical and Biomedical Analysis 2011; 28; 55(1): 23–30.
101 - Nakamura N. Inhibitory effects of some traditional medicines on proliferation of HIV-1 and its protease. Yakugaku Zasshi 2004; 124: 519–529.
102 - Chen SX, Wan M, Loh BN.Active constituents against HIV-1 protease from Garcinia Mangostana. Planta Medica 1996; 62(4): 381–382.
103 - Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology 2002–2003; 70(4): 229–236.
104 - Otake T, Mori M, Ueba N, Sutardjo S, Kusumoto IT, Hattori M, Namba T. Screening of Indonesian plant extracts for antihuman immunodeficiency virus-type1 (HIV-1) activity. Phytotherapy Research 1995; 9: 6–10. 13.
105 - Calabrese C. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytotherapy Research 2002; 14: 333–338.
106 - Kim HJ, Woo ER, Shin CG. A new flavonol glycoside gallate ester from Acer okamotoanum and its inhibitory activity against human immunodeficiency virus-1 (HIV-1) integrase. Journal of Natural Products 1998; 61: 145–148.
107 - Lin YM, Anderson H, Flavin MT, Pai YSH, Mata-Greenwood E, Pengsuparp T, Pezzuto JM, Schinazi RF, Hughes SH, Chen FC. In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. Journal of Natural Products 1997; 60(9): 884–888.
108 - Boyd MR, Hallock YF, Cardellina II JH, Manfredi KP, Blunt, JW, McMahon JB, Buckheit RW, Bringmann G, Schaeffer M. Anti-HIV michellamines from Ancistrocladus korupensis. Journal of Medicinal Chemistry 1994; 37(12): 1740–1745.
109 - Li HY, Sun NJ, Kashiwada Y, Sun L, Snider JV, Cosentino LM, Lee KH. Anti-AIDS agents, 9. Suberosol, a new C31 lanostane-type triterpene and anti-HIV principle from Ployalthia suberosa. Journal of Natual Products 1993; 56(7): 1130–1133.
110 - Yu D, Morris-Natschke SL, Lee KH. New developments in natural products-based anti AIDS research. Medicinal Research Reviews 2007; 27(1): 108–132.
111 - Zhu, K, Cordeiro ML, Atienza J, Robinson EW, Chow S. Irreversible inhibition of human immunodeficiency virus type integrase by dicaffeoylquinic acids. Journal of Virology 1999; 73(4): 3309–3316. 23.
112 - Yao XJ, Wainberg MA, Parniak MA. Mechanism of inhibition of HIV-1 infection in vitro by purified extract of Prunella vulgaris. Journal of Virology 1992; 187(1): 56–62.
113 - Bessong PO, Obi CL, Andreola ML, Rojas LB, Pouysegu L, Igumbor E, Meyer JJ, Quideau S, Litvak S. Evaluation of selected South African medicinal plants for inhibitory properties against human immunodeficiency virus type 1 reverse transcriptase and integrase. Journal of Ethnopharmacology 2005; 99(1): 83–91. 34.
114 - Ahn MJ. Inhibition of HIV-1 integrase by galloyl glucoses from Terminalia chebula and flavonol glucoside gallates from Euphorbia pekinensis. Planta Medica 2002; 68: 454–457.
115 - WHO. Microbicides.
116 - Miller C, Rosenberg Z, Bischofberger N. Use of topical PMPA to prevent vaginal transmission of SIV. Presented at: 9th International Conference on Antiviral Research, Japan, 19–24 May 1996.
117 - Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329(5996): 1168–1174.
118 - Cutler B, Justman J. Vaginal microbicides and the prevention of HIV transmission. Lancet Infectious Diseases 2008; 8: 685–697.
119 - Hicks DR, Martin LS, Getchell JP, Heath JL, Francis DP, McDougal JS, et al. Inactivation of HTLV-III/LAV-infected cultures of normal human lymphocytes by nonoxynol-9 in vitro. Lancet. 1985; 2: 1422–1423.
120 - Wyrick PB, Knight ST, Gerbig DG, Jr, Raulston JE, Davis CH, Paul TR, et al. The microbicidal agent C31G inhibits Chlamydia trachomatis infectivity in vitro. Antimicrobial Agents and Chemotherapy 1997; 41: 1335–1344.
121 - Piret J, Desormeaux A, Bergeron MG. Sodium lauryl sulfate, a microbicide effective against enveloped and nonenveloped viruses. Current Drug Targets 2002; 3: 17–30.
122 - Abdool Karim SS, Richardson BA, Ramjee G, Hoffman IF, Chirenje ZM, Taha T, et al. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS. 2011; 25: 957–966.
123 - Tyssen D, Henderson SA, Johnson A, Sterjovski J, Moore K, La J, et al. Structure activity relationship of dendrimer microbicides with dual action antiviral activity. PLoS One 2010; 5: e12309.
124 - O’Loughlin J, Millwood IY, McDonald HM, Price CF, Kaldor JM, Paull JR. Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose ranging, phase I study. Sexually Transmitted Diseases 2010; 37: 100–104.
125 - Herrera C, Cranage M, McGowan I, Anton P, Shattock RJ. Reverse transcriptase inhibitors as potential colorectal microbicides. Antimicrobial Agents and Chemotherapy 2009; 53: 1797–1807.
126 - Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329: 1168–1174.
127 - FHI and the Centre for the AIDS Programme of Research in South Africa. Factsheet: Results of the CAPRISA 004 trial on the effectiveness of tenofovir gel for HIV prevention. Research Triangle Park, NC USA, July 2010.
128 - Joshi SN, Katti U, Godbole S, Bharucha K, B KK, Kulkarni S, et al. Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India. Transactions of the Royal Society of Tropical Medicine and Hygiene 2005; 99: 769–774.
129 - Joshi SN, Dutta S, Kumar BK, Katti U, Kulkarni S, Risbud A, et al. Expanded safety study of Praneem polyherbal vaginal tablet among HIV-uninfected women in Pune, India: a phase II clinical trial report. Sexually Transmitted Infections 2008; 84: 343–347.