Development of a microbicide-releasing diaphragm as an HIV prevention strategy

Contraceptive diaphragms offer a discreet method of pregnancy protection that women can use when needed with no side effects. Incorporating antiretroviral HIV microbicides into such devices may also provide protection against HIV infection. The paper gives a brief outline of the work being conducted by PATH, CONRAD and QUB on the development of a microbicide-releasing SILCS diaphragm. The design, engineering and manufacturing challenges that have been encountered will be discussed, as well as the potential impact such a device could have in the developing world.

Progesterone release from a silicone intravaginal ring in pigtailed macaques

Background: Heterosexual HIV transmission continues to spread worldwide. Intravaginal rings (IVRs) formulated with antiretroviral drugs hold great promise for HIV prevention in women. IVRs provide the benefit of being coitally-independent and coitally-covert for an extended period. As a proof-of-concept, we tested the in vivo release of progesterone from a silicone elastomer vaginal ring device. Methods: Six female pig-tailed macaques were treated with a GnRH agonist (Lupron) prior to ring placement. Four macaques received a progesterone-loaded silicone ring, and two macaques received a blank silicone ring. Blood, vaginal swabs, CVL, and/or biopsies were collected during ring placement, and after ring removal. Results: The median plasma progesterone levels for macaques with a progesterone IVR were 13,973 pg/ml (day 3), 12,342 pg/ml (day 7), 10,112 pg/ml (day 14), 8445 pg/ml (day 21) and 8061 pg/ml (day 28), with a significant decrease from day 14 to day 21 (P = 0.0286). The median plasma progesterone levels for macaques with a blank IVR were 221±±± ±±88 pg/ml. Macaques with a progesterone IVR had CVL progesterone levels of 20,935 pg/ml (day 7), 6892 pg/ml (day 21) and 11,515 pg/ml (day 28). Macaques with a blank IVR had CVL progesterone levels of 29 �± 13 pg/ml. There were no disturbances to the normal vaginal microflora, and plasma and CVL cytokine analysis did not indicate a proinflammatory response due to ring placement. The vaginal biopsies did not display any pathology following ring removal. Overall, the IVRs were well tolerated without any indication of inflammation or significant changes in the vaginal compartment.

Vaginal microbicides for the prevention of HIV transmission

The human immunodeficiency virus (HIV) kills more people worldwide than any other infectious disease. Approximately 42 million people, mostly in Africa and Asia, are currently infected with HIV (Figure 3.1), and 5 million new infections occur every year (AIDS Epidemic Update, 2002). It is estimated that 22 milIion people have died since the first clinical evidence of AIDS (acquired immunodeficiency syndrome) emerged in 1981 ('Mobilization for Microbicides' ~ The Rockfeller Foundation). HIV is generally transmitted in one of three ways: through unprotected sexual intercourse, blood-to-blood contact, and mother-to-child transmission. Once the virus has entered the body, it invades the cells of the immune system and initiates the production of new virus particles with concomitant destruction of the immune cells. As the number of immune cells in the body slowly declines, weight loss, debilitation, and eventually death occur due to opportunistic infections or cancers. Although AIDS is presently incurable, highly active antiretroviral therapy (HAART), where a cocktail of potent antiretroviral drugs are administered daily to HIV-positive patients to control the viral load, has resulted in dramatic reductions in HIV-related morbidity and mortality in the developed world

Illness perceptions, beliefs and prevention of Type 2 Diabetes among British Pakistani mothers and young British Pakistani women

The prevalence rates of type2 diabetes mellitus (T2DM) continues to rise among British Pakistanis. The aim of this project was to explore T2DM perceptions and any preventative intentions among British Pakistani women and to discover whether they are doing anything to prevent the onset in themselves and their families. Initially a systematic review was conducted to investigate 20 existing prevention interventions and to assess their effectiveness (n=12,419). Mixed methods approach was adopted and three studies were conducted. The first study consisted of two focus groups with T2DM mothers (n=8) and three focus groups with non-T2DM mothers (n=17). The second study consisted of four focus groups young British Pakistani females (n=11). All focus groups were transcribed verbatim and analysed using thematic analysis. Following these a quantitative study was undertaken comprising of a questionnaire survey; 12 prevention-perception items (derived from the qualitative data) and the Illness-Perception Questionnaire Revised (IPQ-R) using participants from the same populations: T2DM mothers (n=41), non-T2DM mother (n=47) and young women (n=42). Results were analysed using multiple/hierarchical regression. The systematic review highlighted that the most effective prevention programmes focussed on behaviour and lifestyle with a combination of support and education to participants. The research studies demonstrated that T2DM was seen as an older person’s disease to be dealt with if/when it happens. T2DM mothers demonstrated knowledge and prevention understanding. There were non-significant relationships between prevention perceptions and T2DM illness perceptions across all three groups. The finding of this thesis emphasised that lifestyle interventions are crucial to aiding T2DM preventions as a good healthy diet and regular physical activity are the key components to T2DM prevention, and the importance of personal experience in perceived severity and lay-beliefs regarding T2DM and on family/cultural influences in British-Pakistanis. The findings of this project can be used to design culturally specific interventions towards preventing T2DM in the British Pakistani community.