Male Circumcision IS as Good as an HIV Vaccine Kelly Curran Director HIV-AIDS-ID, Harshad Sanghvi Vice President & Medical Director 2008 Global Health Mini-University Friday, September 12, 2008

QUIZ Hard Q: What % of sexually active high school students in the US used a condom in their last sex encounter Harder Q: What % of sexually active high school student in the US decide not to have sex because a condom was not immediately available Hardest Q: What % of sexually active high school students in the US decide not to have sex because the male partner was not circumcised Headline Condom use at most recent sexual intercourse among sexually active high school students increased from 46 percent in 1991 to 63 percent in 2005. Over the past two years condom use has remained constant. Less than 10% 3. I do not knowP: no one has asked this q

Session Objectives Show that MC is Effective in preventing HIV infection Safe Acceptable in traditionally non circumcising communities Discuss Challenges in implementing MC at scale in low resource settings How MC advocacy, education, counseling, training, and services can be integrated in ongoing HIV prevention programs The earliest documentary evidence for circumcision is from Egypt. Tomb artwork from the Sixth Dynasty (2345–2181 B.C.) shows circumcised men, and one relief from this period (Ankh Mahor) shows the rite being performed on standing adult males Genesis (17:11) places the origin of the rite among the Jews in the age of Abraham who lived around 2000 B.C.

Male Circumcision Definition Male Circumcision (MC) is the complete surgical removal of the prepuce (foreskin) covering the head (glans) of the penis In many countries MC is conducted in the newborn period; in others it is done as a rite of passage to adulthood WHO and UNAIDS estimate that globally about 30% of males are circumcised. In Africa, nearly 2/3 of men are circumcised.

Previously Recognized Benefits of Circumcision Human Papilloma Virus (HPV) 63% reduction in circumcised men Cervical cancer in female partners 2.0 – 5.8 times more frequent in women with uncircumcised partners Urinary tract infections in infants 12 fold increased risk in uncircumcised boys Syphilis 1.5-3.0 fold increased risk in uncircumcised men Chancroid 2.5 fold increased risk in uncircumcised men Invasive penile cancer in men 22 times more frequent in uncircumcised men Mostly observational studies : No RCTs

Correlation of Male Circumcision and HIV Prevalence Sub-Saharan Africa 40 Swaziland 30 Botswana Lesotho HIV prevalence in adults (%), 2005 20 Zimbabwe South Africa Zambia Mozambique Malawi 10 Kenya Tanzania Cameroon Uganda Angola Ghana Madagascar Benin 20 40 60 80 100 Male circumcision prevalence (%)

MC and HIV Infection: More Evidence Meta-analysis by Weiss et al shows that MC is associated with 50% lower rate of HIV infection Quinn demonstrates in Rakai, that partners of HIV positive women who are uncircumcised had an HIV incidence of 6.7/100 py) while partners of circumcised men 0/50 (p = 0.004) (NEJM 2000) Biologists find that the prepuce contains many Langerhans (HIV target) cells which are easily infected with HIV in vitro Biological plausibility Inner mucosa of foreskin is rich in HIV target cells External foreskin/shaft keratinized and not vulnerable After circumcision, only vulnerable mucosa is meatus Foreskin is retracted over shaft during intercourse Large inner mucosal surface exposure Micro-tears, especially of frenulum Intact foreskin associated with infections Genital ulcer disease Balanitis/phimosis Possible increased HIV entry or shedding

Male Circumcision: Best Evidence Randomized controlled trials are the gold standard in health research 10,000 uncircumcised, HIV-negative men enrolled Intervention group underwent MC in clinical setting Control group “delayed” MC for 24 months, or end of the trial All participants received extensive counseling on HIV prevention, risk reduction and condoms Auvert et al, PloS med 2005, Gray et al, Lancet 2007, Bailey et al, Lancet 2007,

Clinical Trial Results All three clinical trials stopped early due to efficacy MC was so protective that it was unethical to continue to withhold it from the control group MC reduced female to male HIV transmission by approximately 60% Orange Farm Rakai Kisumu Population Semi-urban Rural Urban MC Rate 20% 16% 10% HIV incid. 1.6% 1.3% 1.8% Age Range 18-24 yrs 15-49 yrs 18-24 yrs Sample size 3,128 5,000 2784 Completion April, 2005 June, 2007 Sept, 2007 Interim DSMB Nov, 2004 Dec, 2006 Auvert et al, PloS med 2005, Gray et al, Lancet 2007, Bailey et al, Lancet 2007,

Male Circumcision for HIV Prevention Depending on HIV prevalence in the area, we need to do 5 to15 MCs procedures to prevent 1 new HIV infection (numbers needed to treat) MC is not only cost-effective, it is actually cost-saving given the high costs of ART NNT for Measles vaccine is about 120, For AMTSL to prevent PPH/severe PPH 16/100 Male circumcision protects men from HIV infection

Adverse Events Hemorrhage, hematoma, infection, severe pain, dysuria Kenya trial: 21 events (1.5%) Uganda trial: 84 events (3.6%) Zambia: MC services: 3.6% Male circumcision provided in health settings is safe

Effect of MC on Male to Female Transmission Discordant couple study from Rakai, Uganda: circumcised men 30% less likely to transmit to female partners Clinical trial of MC for HIV+ men found that recently circumcised HIV+ men may be more likely to transmit to female partners Take home messages: MC should be targeted to HIV-negative men If HIV+ men request MC, they must be STRONGLY counseled to abstain from sex for at least 6 weeks / until wound is fully healed Benefit for women partners of HIV positive men who have MC still controversial

Acceptability Studies in Non-Circumcising Communities (9 countries) Male circumcision is Universally perceived to improve hygiene Widely thought to reduce risk of STI thought to reduces risk of HIV by some Biggest barriers to MC are cost, and concerns about safety (risk of infection or mutilation), and pain Most communities want safe, affordable MC services to be available. Westercamp and Bailey 2006

Estimated number of uncircumcised males (Africa, under age 49)* South Africa Uganda Sudan Tanzania Malawi Zimbabwe Zambia Rwanda Mozambique Burundi Nigeria Congo, Dem Rep Ethiopia Kenya Chad Namibia Burkina Faso CAR Botswana 12.0 Sierra Leone Ghana Lesotho Swaziland Côte d’Ivoire Liberia Angola Guinea Benin Madagascar Congo, Rep Cape Verde Cameroon Togo Niger Senegal Mali Eritrea Somalia 0.5 10.7 0.5 5.5 0.5 5.4 0.5 5.2 0.3 5.1 0.3 4.5 0.3 4.1 0.2 3.8 0.2 3.5 0.2 3.1 0.2 3.0 0.2 2.8 0.2 TOTAL: ~ 80 million 2.7 0.1 0.9 0.1 0.8 0.1 0.7 0.1 0.7 0.1 0.7 0.1 * Less than 0.1: Gambia, Guinea-Bissau, Gabon, Mauritania, Equatorial Guinea, Djibouti, Mauritius, Libya, Comoros, Algeria, Egypt, Morocco, Tunisia, Sao Tome and Principe, Seychelles. * Assumes uniform MC rate across age groups within each country Sources: U.S. Census Bureau, DHS, Williams et al, team analysis

Percentage of uncircumcised males willing to get circumcised Uganda (1999) Zimbabwe (2005) South Africa (2005) Swaziland (2006) South Africa (2003) Botswana (2003) Kenya 29% 45% Huge unmet need for male circumcision 51% 54% 59% 61% 70% 73% Avg: 55% Sources: Bailey et al, Halperin et al, Tsela et al, Rain-Taljaard et al, Scott et al, Lagarde et al, Mattson et al, Kebaabetswe et al

% of Participants Who Would Choose to Circumcise a Male Child, if Offered in a Safe Hospital Setting, Free of Charge: Botswana (data shown only for responses following informational session) % Background: Male circumcision is known to reduce the risk of acquiring HIV, but few studies have been performed to assess its acceptability among either children or adults in sub-Saharan Africa. Methods: We conducted a cross-sectional survey in nine geographically representative locations in Botswana to determine the acceptability of male circumcision in the country, as well as the preferred age and setting for male circumcision. Interviews were conducted using standardized questionnaires both before and after an informational session outlining the risks and benefits of male circumcision. Results: Among 605 persons surveyed, the median age was 29 years (range 18 – 74 years), 52% were male, and > 15 tribal groups were represented. Before the informational session, 408 (68%) responded that they would definitely or probably circumcise a male child if circumcision was offered free of charge in a hospital setting; this number increased to 542 (89%) after the informational session. Among 238 uncircumcised men, 145 (61%) stated that they would definitely or probably get circumcised themselves if it were offered free of charge in a hospital setting; this increased to 192 (81%) after the informational session. In a multivariate analysis of all participants, persons with children were more likely to favor circumcision than persons without children (Adjusted Odds Ratio 1.8, 95% CI = 1.0, 3.4). Most participants (55%) felt that the ideal age for circumcision is before 6 years, and 90% of participants felt that circumcision should be performed in the hospital setting. Conclusions: We conclude that male circumcision is highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy is supported by clinical trials. N=605 N=238 N=78 N=289 Source: The Botswana-Harvard AIDS Institute Partnership

Jhpiego’s Work in MC Clear international guidance now available. 2002: Co-sponsored international consensus meeting on MC for HIV Prevention with USAID and PSI 2003-2005: Implemented pilot MC / Male RH project in Lusaka, Zambia 2005/6: developed International reference manual titled Male Circumcision Under Local Anaesthesia with WHO 2007: First regional MC course / pilot test of MC courseware 2008: Clinical Training Skills Course for MC Experts. Participants from Uganda, Kenya, Swaziland, Lesotho and Zambia 2008: second regional MC course. Participants from Ethiopia, Kenya, Rwanda, Swaziland, Uganda, USA and Zambia 2008: Newborn MC consultation in Nigeria Clear international guidance now available.

Results and Lessons Learned Participants with minimal surgical skills can be trained to competency in short courses Training more that one provider per site is critical Adverse events are minimal Standardized training materials work well Investment in developing high performing training sites is essential Early follow up of trainees reinforces training. All participants with previous surgical experience can become competent in the MC procedure during the course Participants with little surgical experience need more practice with surgical skills (i.e., suturing) All participants become competent in counseling and group education skills during the course Participants are better able to use their new skills if they are trained as a team rather than one provider per facility Email groups allow MC “alumni” to stay in touch to share challenges and solutions

Frequently Raised Issues: Risk Compensation Won’t circumcised men believe they are 100% protected and stop using condoms and/or increase their number of sex partners? Response: Valid concern No evidence of risk compensation or disinhibition from the MC trials or post-trial surveillance valid concern so far there is no evidence of risk compensation or disinhibition from the MC trials or post-trial surveillance. The Kenya trial suggests that counseling received before and after MC can actually reduce risky behavior. Modeling data suggest that risk compensation would have to be quite significant to undermine the protective effects of MC.

Frequently Raised Issues: Women’s Issues MC does not help women and might even put them at risk if circumcised men refuse condoms or resume sex too early. We should focus on microbicide research and the female condom instead of wasting our energy on something that won’t help women. Response: MC scale up will reduce HIV incidence in women as well as men MC communication should also target women so that they know the importance of abstinence during wound healing There is no evidence that circumcised men are abandoning condoms There are important gender issues to address in MC, but MC scale up will reduce HIV incidence in women as well as men. While recently circumcised, HIV+ men who resume sex too early appear to be at high risk to transmit the virus. However, men can only transmit HIV if they are infected, and the target population for MC scale up will be HIV-negative men. MC services should include provider-initiated CT so that men learn their HIV status as well as counseling on the importance of abstinence during wound healing (6 weeks). MC communication efforts should target women so that they also know the importance of abstinence during wound healing. So far there is no evidence that circumcised men are abandoning condoms; if anything data from the trials suggests that circumcised men find it easier to use a condom.

Frequently Raised Issues: Surgical Capacity I would love to implement MC in my country but we have limited surgical capacity with long waiting lists. How can I justify using our scarce surgical resources for non-emergency surgery? Response: It will not be easy to reach thousands of young men Train clinical officers and nurses to provide MC. “import” volunteer surgeons from other countries. Train nurse-midwives to provide newborn MC. This will reduce the numbers of adolescents & adults who need MC This is indeed a major challenge. MC is an investment in the future that will ultimately reduce the burden on healthcare workers as fewer people will need HIV clinical care; in fact, MC is not only cost-effective it is cost-saving. In high prevalence countries as few as 5 to 15 MCs will prevent one HIV infection. That said, it won’t be easy to reach hundreds of thousands of young men. Solutions include task shifting from doctors to clinical officers or nurses and “importing” volunteer surgeons from other countries. If nurse-midwives are taught to provide newborn MC the numbers of adolescents and adults who need MC will eventually decrease. Clinical officers and nurses who have been taught adult MC will be available for other minor surgeries, freeing up doctors and surgeons to work on more complex cases. Ideally, MC can build surgical capacity.

Frequently Raised Issues: Traditional Circumcisers In our country we have many traditional circumcisers. Why can’t we train them to do MC for the non-circumcising communities? Response: Most men from non-circumcising communities want medical, not traditional circumcision Complication rates in traditional circumcision are very high (more than 30%) Medical circumcision is safer and less painful because local anesthesia is used. Healing time is faster because the wound is sutured The acceptability studies show that most men from non-circumcising communities want medical, not traditional circumcision. In addition, research in Kenya has found very high (more than 30%) complication rates in traditional circumcision. Medical circumcision is safer and less painful because local anesthesia is used. Healing time is faster because the wound is sutured. WHO, UNAIDS and PEPFAR encourage training of health professionals rather than traditional circumcisers

Frequently Raised Issues: Traditional Circumcisers We want to scale up medical MC in our country but the traditional circumcisers are opposed to it, and they are very powerful in the community. Response: Involve the traditional circumcisers in the program to get their input. Encourage traditional circumcisers to do the whole initiation ceremony and all of the education for the initiates but have the MC done by a skilled provider

Frequently Raised Issues: Newborn MC I heard that newborn MC is much easier to perform than adult MC. Can we just train nurse- midwives to do newborn MC and forget about the adults? Response: Newborn MC is easier and cheaper than adult MC Newborn MC is an important investment but won’t have an impact on HIV incidence for about 25 years Ideally both adult and newborn MC should be scale up simultaneously It is true that newborn MC is much easier than adult MC. In addition, there are no concerns about sex before wound healing. However, if your country just focuses on newborn MC, you will miss the opportunity to reduce HIV incidence among adults. Newborn MC is an important investment but won’t have an impact on HIV incidence for about 25 years. Ideally both adult and newborn MC should be scale up simultaneously.

Frequently Raised Issues: Newborn MC During antenatal care the nurse-midwife asked me if I wanted to have my child circumcised (if it is a boy). I always thought circumcision was for adolescents. Is it safe to circumcise such a small baby? Response: Newborn circumcision is safe for healthy babies if done by a trained health professional The wound heals much faster than in adolescents or adults Newborn circumcision is safe for healthy babies if done by a trained health professional. In fact, the wound heals much faster than in adolescents or adults. The nurse midwife will explain how to care for the wound. It is important to follow these instructions and to return if there are any problems. If you decide not to circumcise your son as an infant but want to circumcise him later it is probably best to wait until he is an adolescent. Toddlers and young children usually can not hold still for MC under local anesthesia and there are risks with general anesthesia (putting the child to sleep for surgery).

Conclusion Male circumcision is the most effective HIV prevention strategy we have right now that is not user dependant User dependant methods such as abstinence, being faithful, and condoms provide additional benefits

ABC & MC: Combination Prevention for HIV Vaccine            Microbicides