Which of the following statement(s) about research and development of microbicides is/are true:

• a)
  

  Microbicides are being developed for women for both vaginal and rectal use.

  
  
• b)
  

  Although several candidate microbicides have been tested, there is no proof that microbicides can prevent HIV in women.

  
  
• c)
  

  The only way to demonstrate a vaginal microbicide is effective in preventing HIV is to conduct large efficacy trials involving thousands of HIV-negative women.

  
  
• d)
  

  Vaginal drug concentrations of the microbicide correlate with protection against HIV infection.

  
  
• e)
  

  The results of challenge studies in monkeys have correlated closely with protection against HIV in humans.

Which of the following mechanisms of action have been tested for the effectiveness of candidate microbicides in preventing HIV infection?

• a)
  

  Viral integrase enzyme inhibitors.

  
  
• b)
  

  Vaginal defence enhancers.

  
  
• c)
  

  Viral entry inhibitors.

  
  
• d)
  

  Viral DC-sign inhibitors.

  
  
• e)
  

  Viral replication inhibitors.

Which of the following is/are reasons why tenofovir is considered a good candidate for development as a microbicide:

• a)
  

  Tenofovir is widely used as the drug of choice in first-line treatment regimens to treat acquired immune deficiency syndrome (AIDS).

  
  
• b)
  

  Tenofovir is a large molecule with poor systemic absorption thereby reducing the risk of systemic side effects from topical use.

  
  
• c)
  

  Tenofovir has a good safety profile.

  
  
• d)
  

  Tenofovir has a long half-life.

  
  
• e)
  

  Tenofovir was effective in preventing simian immunodeficiency (SIV) virus in monkey models.

The efficiency of HIV transmission from men to women during sexual intercourse is relatively inefficient, although several biological factors have been associated with increased risk of infection. These include:

• a)
  

  The presence of ulcerative sexually transmitted infections.

  
  
• b)
  

  The presence of certain aerobic bacterial species, such as Lactobacilli.

  
  
• c)
  

  The viral load of the male partner.

  
  
• d)
  

  The presence of cervico-vaginal mucous.

  
  
• e)
  

  Bacterial vaginosis.

Adolescent girls are at increased risk of HIV infection because:

• a)
  

  Adolescent girls have cervical ectropion and a larger transformation zone.

  
  
• b)
  

  Columnar epithelia are more susceptible than stratified squamous ones.

  
  
• c)
  

  The onset of puberty and higher levels of sex hormones suppress innate and adaptive responses in the genital tract.

  
  
• d)
  

  They have a greater prevalence of aerobic bacteria.

  
  
• e)
  

  Protective Lactobacilli only tend to colonise the genital tract with onset of sexual activity.

The first-generation topical microbicides to prevent HIV infection, nonoxynol-9 (N-9) and cellulose sulfate, were associated with risk of infection because:

• a)
  

  They caused microulceration of the vaginal epithelial barrier.

  
  
• b)
  

  They dampened inflammatory signals in the genital tract, thereby suppressing effective immunity.

  
  
• c)
  

  They altered protective vaginal microbial flora.

  
  
• d)
  

  They disrupted the phospholipid membrane of cells, making them less effective at blocking infection.

  
  
• e)
  

  They made submucosal target cells easier to reach.

Several combination strategies have been suggested to improve the efficacy of the current anti-retroviral drug containing topical microbicides. These include:

• a)
  

  Strategies to reduce genital tract inflammation, such as inclusion of an anti-inflammatory drug together with the microbicidal agent.

  
  
• b)
  

  Treating the causes of inflammation, such as better management and more intensive treatment of sexually transmitted infections.

  
  
• c)
  

  Pro-biotic treatment with commensal Lactobacillus species.

  
  
• d)
  

  Douching agents.

  
  
• e)
  

  Addition of estrogen containing compounds.

Which of the following is/are considered an advantage(s) of a topical microbicide formulated as a gel?

• a)
  

  Female controlled.

  
  
• b)
  

  Limited systemic absorption.

  
  
• c)
  

  Lubricating properties.

  
  
• d)
  

  They are suitable for drugs that are unstable in aqueous solution.

  
  
• e)
  

  Low side-effect potential.

Which of the following prevent(s) HIV by allosterically inhibiting reverse transcription?

• a)
  

  Tenofovir.

  
  
• b)
  

  Dapivirine.

  
  
• c)
  

  RC-101.

  
  
• d)
  

  Nonoxynol-9.

  
  
• e)
  

  Maraviroc.

When formulating a vaginal microbicide for HIV prevention, which of the following must be taken into consideration?

• a)
  

  The pharmaceutically active compound must be stable in the vehicle.

  
  
• b)
  

  Product must distribute throughout the vaginal or rectal compartment.

  
  
• c)
  

  pH must be compatible with the mucosal surfaces that the microbicide is intended to be applied to.

  
  
• d)
  

  Osmolality must be compatible with the mucosal surfaces that the microbicide is intended to be applied to.

  
  
• e)
  

  Films and solid tablets must have adequate disintegration over time.

Which factor(s) make(s) designing prevention trials different to treatment trials?

• a)
  

  There is essentially no difference.

  
  
• b)
  

  They require smaller sample sizes.

  
  
• c)
  

  Identifying the population at risk is often more difficult in prevention trials.

  
  
• d)
  

  Specific patient groups are more difficult to target.

  
  
• e)
  

  Many people recruited are not at risk of the disease of interest.

Which of the following is a key assumption made for the power calculation when designing a microbicide trial?

• a)
  

  Human immunodeficiency virus (HIV) incidence.

  
  
• b)
  

  Adverse reactions to the product.

  
  
• c)
  

  Adherence to the product.

  
  
• d)
  

  Acceptability of the product.

  
  
• e)
  

  Patient drop out rates.

Why is measuring adherence essential in microbicide trials?

• a)
  

  To encourage participants to use the product.

  
  
• b)
  

  To aid interpretation of product efficacy.

  
  
• c)
  

  To put the trial result in context with other trials.

  
  
• d)
  

  To engage participants in the study.

  
  
• e)
  

  It is a regulatory requirement.

What is the purpose of the independent data monitoring committee (IDMC)?

• a)
  

  To estimate the sample size of the trial.

  
  
• b)
  

  To provide regulatory guidance and oversight.

  
  
• c)
  

  To protect the trial sponsors and investigators.

  
  
• d)
  

  To protect the safety of study participants.

  
  
• e)
  

  To provide independent review of the unblinded accruing trial data.

Reproductive health-related exclusion criteria that may be used to screen women out of microbicide trial participation include the following:

• a)
  

  Non-pregnant woman.

  
  
• b)
  

  A woman not planning to fall pregnant over trial duration.

  
  
• c)
  

  A woman wanting to use contraception.

  
  
• d)
  

  A woman planning a pregnancy over the trial duration.

  
  
• e)
  

  None of the above.

The following microbicides also have contraceptive properties:

• a)
  

  Tenofovir.

  
  
• b)
  

  Savvy.

  
  
• c)
  

  Cellulose sulfate.

  
  
• d)
  

  Nonoxynol 9.

  
  
• e)
  

  Cellulose sulfate and nonoxynol 9 combined.

Eligible contraceptive methods in CAPRISA 004 included the following:

• a)
  

  Female condom.

  
  
• b)
  

  Depot medroxyprogesterone acetate.

  
  
• c)
  

  Male condom.

  
  
• d)
  

  Diaphragm.

  
  
• e)
  

  Cervical cap.

A woman who fell pregnant during which of the trials below was removed from the study upon pregnancy diagnosis?

• a)
  

  Family Health International (FHI) Savvy/Nigeria trial.

  
  
• b)
  

  CONRAD Cellulose Sulfate trial.

  
  
• c)
  

  Population Council Carraguard trial.

  
  
• d)
  

  Microbicide Development Program (MDP) 301 trial.

  
  
• e)
  

  Microbicide Trials Network (MTN) 003 trial.

The following is/are key issues in the HIV prevention research agenda for women:

• a)
  

  Developing a microbicide that allows women to have a female-controlled prevention method.

  
  
• b)
  

  Strengthening infrastructure and social grants.

  
  
• c)
  

  Combining microbicides with barrier methods.

  
  
• d)
  

  Including men in HIV prevention efforts to protect women.

  
  
• e)
  

  Couple counselling to enhance joint responsibility.

Important sub-populations that require special attention for fighting the HIV epidemic in Sub-Saharan Africa include:

• a)
  

  Women aged 24 years and younger.

  
  
• b)
  

  Men who have sex with men.

  
  
• c)
  

  Pregnant women.

  
  
• d)
  

  Intravenous drug users.

  
  
• e)
  

  Hepatitis B +ve women.

Critical milestones in the HIV pandemic in relation to women include:

• a)
  

  Discovery of the HIV virus in men who have sex with men.

  
  
• b)
  

  Discovery of HIV in IV drug abusers.

  
  
• c)
  

  Condoms used as the main means of HIV prevention.

  
  
• d)
  

  Zena Stein’s commentary in the American Journal of Public Health on the need to increase the HIV prevention strategies available to women.

  
  
• e)
  

  CAPRISA 004 suggesting that a microbicide product shows efficacy at protecting against HIV infection.

Important areas to consider in the future of HIV research in women include:

• a)
  

  Multi-disciplinary research extending across research fields, including the behavioural and biomedical disciplines.

  
  
• b)
  

  Placing HIV prevention within the context that women currently find themselves in.

  
  
• c)
  

  Empowering women and enabling them to use what is currently available.

  
  
• d)
  

  Looking at interventions that address broader social and political issues of society.

  
  
• e)
  

  Interventions dealing with structural issues of society.

The following statement(s) is/are true about the dapivirine vaginal ring:

• a)
  

  The ring is designed to work against HIV by preventing the virus from replicating, as it is a non-nucleoside reverse transcriptase inhibitor.

  
  
• b)
  

  It is designed to protect against both HIV and herpes simplex virus 2 (HSV-2).

  
  
• c)
  

  The dapivirine vaginal matrix ring is designed to provide sustained release of dapivirine over a minimum of 28 days.

  
  
• d)
  

  Because of its ability to neutralise pathogens in both semen and vaginal secretions, it is being evaluated as a bi-directional method of protection against HIV for both partners.

  
  
• e)
  

  Because of the novel ring technology, if found effective, is likely to be a costly HIV prevention method once approved for use.

Future microbicide product development efforts must continue to focus on multiple formulations and delivery methods (e.g. vaginal ring, tablet, film and gel) because:

• a)
  

  Previous safety studies of the ring have shown low participant adherence, indicating that alternative microbicide formulations are needed to improve adherence rates.

  
  
• b)
  

  Male partners find the dapivirine ring to be an unacceptable form of protection against HIV, as it affects their sexual pleasure during intercourse.

  
  
• c)
  

  No single HIV prevention option will be appropriate for, or acceptable to, all women.

  
  
• d)
  

  Long-acting products are expected to improve user adherence and acceptability and result in increased product effectiveness.

  
  
• e)
  

  Not all drugs can be optimally formulated in specific dosage forms.

The following statement(s) is/are true about HIV prevention for young women in low-income countries:

• a)
  

  Young women are at low risk for HIV infection.

  
  
• b)
  

  Prevention options that require partner consent are most suitable for young women.

  
  
• c)
  

  Several prevention methods already exist for these women.

  
  
• d)
  

  HIV prevention is a serious public health priority, as more than 60% of those infected are aged between 15 and 24 years.

  
  
• e)
  

  HIV prevention is not necessary in young women.

Translating positive findings from effectiveness trials into real-life performance in health systems is challenging because:

• a)
  

  Microbicides are not yet available.

  
  
• b)
  

  Health-system performance influences the effectiveness of interventions.

  
  
• c)
  

  Healthcare workers do not focus on HIV prevention.

  
  
• d)
  

  Microbicides are expensive.

  
  
• e)
  

  Quality improvement of the health system has not yet been undertaken.

Implementation science is defined as:

• a)
  

  Scientific study to promote integration of research findings and evidence-based interventions into healthcare policy and practice to improve the quality and effectiveness of health services.

  
  
• b)
  

  Randomised clinical trials to test microbicide interventions.

  
  
• c)
  

  Pre-clinical assessment of microbicides.

  
  
• d)
  

  A research methodology to undertake monitoring and evaluation of programmes.

  
  
• e)
  

  Post-marketing surveillance of health systems.

Barriers to implementing microbicides in low-income countries include:

• a)
  

  Potential for integration into existing health services.

  
  
• b)
  

  Lack of confirmation of effectiveness of candidate microbicides.

  
  
• c)
  

  Low HIV disease burden.

  
  
• d)
  

  Regulatory approval of an effective microbicide.

  
  
• e)
  

  Cost of production.

The following is/are seen as significant challenges to monitoring of microbicide research in low income, high HIV burden countries

• a)
  

  Excluding HIV infection pre-recruitment.

  
  
• b)
  

  Monitoring for HIV conversion during a trial.

  
  
• c)
  

  Detection of pregnancy.

  
  
• d)
  

  Unwillingness to report side effects due to not wanting to have the drug stopped.

  
  
• e)
  

  Detection of coexistent STIs.

Microbicides are an HIV prevention modality that can potentially be rolled out using existing healthcare infrastructure because:

• a)
  

  They are specifically formulated for topical use, which limits systemic toxicities.

  
  
• b)
  

  Users who may benefit most already use existing infrastructure, such as family planning clinics.

  
  
• c)
  

  They are formulated as vaginal rings only.

  
  
• d)
  

  They are already licensed for HIV prevention.

  
  
• e)
  

  They are available over the counter.