WWW.ICAD-CISD.COM New Prevention Technologies Workshop Module 1: Basic definitions Objectives This workshop will: Increase the capacity of media representatives to report on NPT trials with accuracy and sensitivity Build skills amongst community-based organizations to critically analyze media discourse about HIV prevention trials Increase the capacity of community representatives to understand and communicate NPT trial results effectively Warm-Up Exercise Please read the articles that have been provided to you. They all report on the same trial results. Discuss Questions: 1. What is the tone of each article? (Optimistic? Pessimistic?) 2. What conclusion do you come to after reading each article? 3. What information do you feel is missing? Imagine a full spectrum of interventions Point of transmission Prior to exposure Rights-focused behaviour change Male & Female condoms and lubricant Voluntary counselling & testing Treatment to prevent vertical transmission (PMTCT) Sexually transmitted infection screening and treatment Male medical circumcision Preventative vaccines Pre-exposure prophylaxis (PrEP) After infection Antiretroviral treatment Treatment for opportunistic infections Basic care/nutrition Prevention for positives Clean injecting equipment Post-exposure prophylaxis (PEP) Education and rightsfocused behaviour change Vaginal & rectal microbicides Therapeutic vaccines Functional cures Cervical barriers Which NPTs? Vaccines? PrEP? Microbicides? Medical male circumcision? Female condoms? Treatment-as-prevention? MEDICAL MALE CIRCUMCISION Medical male circumcision 3 studies conducted: South Africa, Uganda, Kenya Trials showed: circumcised men about 60% less likely to acquire HIV through unprotected vaginal intercourse WHO published recommendation based on study results Medical male circumcision 60% risk reduction for HIV-negative circumcised men during unprotected vaginal intercourse with HIV+ woman Trials did not show reduction in transmission risk from circumcised HIV+ man to HIV-negative woman In fact, one trial showed opposite trend: increased risk for wives of circumcised HIV+ husband; probably due to resuming sex too soon after circumcision Trials did not provide information on effect of circumcision on HIV transmission during anal sex—for either women or men Challenges with Male Circumcision Public messages must be communicated very clearly: reduces but does not eliminate men’s HIV risk Need to educate about the difference between FGC and male circumcision “Potential harmful outcomes”: condom substitution, surgical complications, inadequate healing time Religious and cultural meanings of circumcision Ethics of promoting circumcision for infant boys FEMALE CONDOMS Female Condoms Or “the internal condom” a thin pouch that a woman can insert in her vagina before sex to prevent pregnancy and sexually transmitted infections (STIs), including HIV FC1: Polyurethane; FC2: nitrile rubber (less noisy, cheaper than FC1) the only proven, female-initiated method of HIV prevention currently on the market can be used vaginally or anally same efficacy as male condoms for STI prevention and contraception Challenges with Female Condoms Almost all (99.6%) condoms distributed globally are male condoms. Only a tiny fraction of women worldwide have access to female condoms. Why? High price: US$0.60 vs. US$0.04 for male condom Perceived and real acceptability issues: cumbersome, hard to use, partners do not like them, taboos around female sexuality Not enough donor and policy-maker support: low interest among some major donors and governments Discomfort among “gatekeepers”: health care providers and HIV and AIDS programme implementers ARV-BASED PREVENTION METHODS ARV-based prevention options Point of transmission Prior to exposure After exposure Preventing vertical transmission (PMTCT+) PrEP Treatment of HIV+ partner Vaginal microbicides (rings) Vaginal microbicides (gels) and rectal microbicides PEP HIV prevention Not ARV-based Male & female condoms Circumcision Clean injecting equipment Vaccines VCT ARV based Vaginal and rectal microbicides Preventing vertical transmission PEP PrEP Treatment for HIV+ partner Comparing ARV-based prevention methods PEP Drugs used Delivery formats Multiple ARVs Oral pills Frequency Daily for 4 weeks of use Preventing vertical Treat HIV+ transmission partners (PMTCT) PrEP Microbicides Tenofovir and Truvada Tenofovir, TMC 120 (daviripine), UC781, MV-150 Nevirapine; combination, if possible (AZT+3tc+ nevirapine) Multiple ARVs Pills, dropper Oral pills, injection Oral pills Vaginal and rectal gels with applicators, vaginal rings, film At least daily At least daily, possible dosing related to exposure Before and possibly after sex, possibly daily dosing Varies from ongoing treatment to doses just before, during, after delivery Why test ARVs to prevent HIV? ARVs already are used to prevent vertical transmission (or PMTCT) PEP already is used to prevent infection after medical accidents or rape Monkeys that get ARVs prior to exposure are less likely to be infected with “monkey forms” of HIV TREATMENT AS PREVENTION Treatment as prevention HIV+ people taking ARVs regularly Does it work at individual level? Treatment = less virus = less transmission Can it work at population level? Increased testing = more knowledge of status = less risk-taking Increased testing = more HIV+ people on treatment = less virus Less risk-taking + less virus = less transmission? Steps needed for “Treatment as prevention” ARVs for prevention Access to treatment Knowledge of status MICROBICIDES VIDEO What is a microbicide? A suppository or a gel applied with an applicator before sex A vaginal ring that stays in place for up to a month We need microbicides that: Are both contraceptive and not contraceptive Help reduce the risk of getting other sexually transmitted infections Are inexpensive and easily available Can be used without a partner’s active cooperation Can be used vaginally or rectally Can be used by HIV+ people (products not based on ARVs) Why would HIV+ people want microbicides? To reduce the risk of co-infection with other HIV strains. To reduce the risk of other sexually transmitted infections, and yeast and bladder infections To allow conception whilst protecting partner 1. Boost vagina’s natural defences 2. Surfactants * 5. Future possibility 4. Stop replication 3. Block binding *STDs: sexually transmitted diseases Comparing ARV-based and non-ARV-based microbicides ARV More potent against HIV May be long lasting Not contraceptive Advantages Disadvantages May be more toxic May cause resistance Unlikely to protect against other sexually transmitted infections Not ARV Could work against HIV and other sexually transmitted infections Could be contraceptive May be less potent against HIV Must be used at time of sex PRE-EXPOSURE PROPHYLAXIS Pre-exposure prophylaxis (PrEP) Experimental HIV prevention strategy that would use ARVs to protect HIV-negative people from HIV infection Taking medicine to prevent rather than to treat a disease or condition. For example: Taking pills to prevent malaria when you travel Using hormonal contraceptives (injections or pills) to prevent pregnancy Taking pills to avoid pneumonia, if you are at risk What makes a drug a good candidate for PrEP? Now being tested: tenofovir (Viread) Truvada (tenofovir+emtricitabine combined) Easy to use: Only one pill required per day (maybe less) Safe: Few side effects in HIV-positive people Powerful: Stays in the bloodstream a long time Unique resistance profiles: If resistance develops, other treatment options still exist Safety concerns? Safety is a critical issue for PrEP use Look carefully at people with pre-existing conditions: hepatitis B and C, kidney problems, bone density Pregnancy, post-menopause (osteoporosis), adolescents (bone formation) Look carefully at drug clearance in people with low body weight, including women and Asians ISSUES AROUND ARV-BASED PREVENTION METHODS Drug resistance More likely if taking only one drug (or one type of ARV) Can still become HIV+ using ARV-based prevention Use by people who don’t know they are HIV+ might lead to resistance? Options for treatment may be more limited, might pass on resistant virus Unanswered questions at this point Think of weeds in a garden If you use weed killer: Some weeds die Others thrive, grow bigger, and take over The weed killer accidentally helps resistant weeds – it takes away all their competition To stop the big weeds: Take away the first weed killer Introduce other weed killers that stop all weeds – big and small Concept for this slide: Jeanne Marrazzo, MD and John Mellors, MD, MTN Next steps for science Gather more data on how PrEP works across populations Address safety concerns through current trials and further research Learn how to monitor widespread resistance Study intermittent use: for example, taking it only when you expect to have sex. Find out about impact on pregnancy and breast feeding Test other ARVs to see if they might also work as PrEP IMMUNE SYSTEM, HIV AND VACCINES VIDEO Vaccines A vaccine is a substance that teaches the body to recognize and defend itself against bacteria and viruses that cause disease. A vaccine causes a response from the immune system— the body's defense system—preparing it to fight, and also to remember how to fight, if exposed to a specific infection. A vaccine is not a cure, but prevents infection or slows disease progression. A vaccine primer 200 years of vaccines Common vaccines Types of immunity: humoral (antibody) and cellmediated An ideal HIV vaccine Preventative or therapeutic? Immune response Challenges in HIV Vaccine Research Designing the vaccine: need a different approach for HIV vaccines Animal models: have not yet accurately predicted how they will work in humans Unknown correlates of protection: don’t know what immune responses will protect an individual from infection HIV mutation: there are many different subtypes of HIV, may require matching vaccines …but on the bright side… Broadly neutralizing antibodies found Precedent from other systems: Success against other viral infections Precedent from animal studies: Longterm control of infection in vaccinated monkeys Immune control of HIV-1: Infected individuals control infection Vaccine trials: In progress GENDER IMPLICATIONS Gender and HIV What do we mean by “gender”? Is it the same as “sex”? What factors influence vulnerability to HIV? What impact does gender have on HIV prevention? For women? For men? For gay men? What women need to protect themselves Social power Protection Technology Economic opportunities Questions women have about ARVbased prevention If I think my husband has HIV, will I be able to get PrEP? Even if the doctor gives me pills, will I be able to keep them for myself? If I use a microbicide, how will I make my man use a condom? More questions women have People will notice if I have to go in for testing and to get my pills. What will they say about me? Will my husband let me go to the clinic? How much will it cost? Where will I get it? Will it make me sick? Can I take PrEP when I am pregnant? Will it hurt my baby? What about breastfeeding?