Reflec%ons on the Role of Discordant Couples and the HIV Epidemic Implementa%on Science and Male Circumcision in Rakai Ron Gray & Maria Wawer Johns Hopkins University
Discordant couples, why are they important? If most infec<ons in a popula<on occur in stable discordant couples, universal tes<ng could iden<fy couples at risk and promote: Couples VCT (Bunnell, Cheru,ch Lancet, 2008) Behavioral risk reduc<on (Allen et al AIDS 2003) Use of PreP Ini<ate ART to prevent transmission (Dieffenbach, Fauci JAMA 2009, Granich et al Lancet 2009)
Premise for focus on discordant couples (Gray et al AIDS 2011) A substan<al propor<on of all transmissions must occur within iden<fiable discordant dyads Can provide couples counseling and mutual disclosure Interven<ons for discordant couples must be efficacious and durable
How Common are Discordant Couples in DHS surveys? (Eyawa et al Lancet Infect Dis 2010) Discordant % of all couples Burkina Faso 2.6 Cameroon 5.1 Ethiopia 1.7 Ghana 3.2 Guinea 1.5 Ivory Coast 3.5 Kenya 7.3 Lesotho 13.6 Malawi 9.7 Rwanda 2.2 Tanzania 7.9 Zimbabwe 12.9 Frequency of discordant couples varies from 1.5 to 13.6% of married couples 47% of discordant couples are female HIV+ Caveats: Only includes couples with both partners iden<fied and tested Excludes couples with absent partners
Frequency of Discordant Couples in the Rakai Cohort (Gray et al AIDS 2011) Pre- ART (N=9434) % AKer ART Available (N=13082) % Not currently Married 36.6 39.4 Currently Married Concordant Nega<ve 38.8 39.0 Discordant 1.8 1.8 Unknown partner status 22.8 19.8 A high propor<on of married persons do not have an iden<fiable partner at <me of survey
Modeling the Contribu%on of HIV Discordant Couples to the HIV Epidemic Dunkle et al Lancet 2008 Used DHS and VCT data from urban Zambia and Rwanda to model the contribu<on of stable HIV- discordant couples to the HIV epidemic. Es<mated 55-93% of new HIV infec<ons occurred within HIV- discordant couples Numerous cri<ques Overes<mated transmission (20% per year) Ignored introduc<on of infec<on into the dyad from external partners
Modeling the Contribu%on of Discordant Couples to HIV Incidence (Coburn et al, Lancet Infect Dis 2011) Contribu<on of discordant couples to HIV incidence varies by propor<on of stable rela<onships in the popula<on and HIV prevalence
Contribu%ons of Discordant Couples to HIV Incidence in Rakai, Uganda (Gray et al AIDS 2011) Pre- ART Availability Propor%on of HIV Incident Infec%on (%) AKer ART Available Propor%on of HIV Incident Infec%on (%) Not married 29.3 42.7 Currently Married Concordant HIV- neg 23.2 26.0 Discordant Couples 18.3 13.7 Unknown partner status 29.3 17.6 Only a minority of incident HIV infec<ons occur among iden<fiable discordant couples
Conclusion Iden<fica<on of HIV- discordant couples is important, but is unlikely to have a major effect on the epidemic because: Discordancy is a transient state, infec<vity is high during acute and recent HIV infec<on (Wawer et al JID 2005) Many HIV+ persons have partners of unknown status Discordant marriages have high rates of dissolu<on (Porter et al Demography, 2004) Most infec<ons occur in unmarried or concordant HIV- nega<ve couples in Rakai Models based on inferred infec<ons may be misleading
Implementa%on Science Research on Male Circumcision (MC) The objective of implementation science is to promote the integration of research findings into policy and practice to improve the uptake, implementation and translation of evidence-based interventions (Padian et al JAIDS 2011)
Implementa<on Science Research on Male Circumcision (MC) Training and achievement of competence Task sharing (MOVE) Task shiking: Physicians versus clinical officers Surgical procedures Sleeve, dorsal slit forceps guided Shang ring, PrePex device Local anesthesia Impact: Post- trial effec<veness and risk behaviors Impact of MC on HIV incidence
MC MOVE: Models for op%mizing the volume and efficiency of MC services. Task Sharing Dino Rech PSI -Assistant prepares site and provides local anesthesia -Surgeon removes foreskin, secures hemostasis and inserts main mattress sutures -Assistant inserts simple sutures and dressing Indicator Pre MOVE MOVE (Sleeve) MOVE (Forceps Guided) Doctor Operating Time (Minutes) 25 50 mins 10 20 mins 5 10 mins # of Clients per hour 1 2/hour 3 5/hour 5 8/hour
Training and achievement of competence All trainees perform 15-20 supervised MCs before cer<fica<on Assessed <me required for surgery and moderate/severe adverse events (AEs) by number of surgeries
Dura%on of surgery by number of procedures performed (Kigundu BJU 2009) Mean duration of circumcision by number of surgeries with 95% CIs 20 25 30 35 40 45 Need ~ 100 surgeries to reach Op<mal <me for circumcision 0-19 20-39 40-59 60-79 80-99 100-199 200-299 300-399 400-499 500-599 600-699 700-799 800-899 900-999 Number of surgeries
Complica%ons by number of surgeries performed aker training (Kigundu BJU 2009) Complications % 10 9 8 7 6 5 4 3 2 1 0 8.8 4 Risk of complica<ons is high immediately aker training 2.2 3.2 2.8 3.1 0-19 20-99 100-299 300-499 500-699 700+ Number of surgeries
Complica%on rates and dura%on of surgery with two procedures and two types of providers (Buwembo, Br J Urol 2011) Sleeve Circumcision (n=1050) Dorsal Slit Circumcision (N=971) Physicians (n=564) Clinical Officers (n=1457) Complications 0.9% 0.6% 0.9% 0.7% Duration of surgery 28.5 min 24.5 min 24.3 min 29.9 min Dorsal slit is faster and as safe as sleeve circumcision Clinical officers were slower, but as safe as physicians
Randomized trial of Local anesthesia (Kigozi et al BJU 2011) Lignocaine alone (N=179) vs mixture of lignocaine and Bupivacaine (N=181) Lignocaine (%) Mixture (%) RR (95% CI) Pain during surgery 17.3 1.7 11.6 (3.5-37.9) Addi<onal anesthesia required 6.7 1.7 4.8 (1.4-17.1) Post- opera<ve pain 68.2 19.3 3.4 (2.3-5.0)
Minimally invasive circumcision: Shang Ring Developed in China Surgical time ~ 5 minutes Removed after 7-9 days Low complication rates reported to date Frees up theater time Study of safety and acceptability in Rakai: how will this work in rural Africa?
- No local anesthesia - Minimal surgical facili<es - No bleeding: foreskin crushed and becomes necro<c - Removed 7-9 days - Minimal safety data (42 cases) PrePex Device Will conduct a stepwise safety and acceptability study in Rakai
MC effectiveness for HIV prevention: Control arm par%cipants post- trial (Kong et al CROI 2011) 0.06 Adj Effec%veness 68% (39-83%) Probability of HIV Detec%on 0.04 0.02 Uncircumcised Circumcised 0.00 T 0 (Last trial visit) 10 20 30 40 months 20
Non-marital sex partners control arm men by MC adoption post-trial Opted for MC No MC p=0.10 p=0.46 Last trial visit Post- trial visit Last trial visit Post- trial visit No difference in behaviors
Condom use with non-marital partners by control arm men post-trial Opted for MC No MC p<0.001 p=0.003 p=0.003 Last trial visit 1 st post- trial visit Last trial visit Post- trial visit Non-use increased in both groups Consistent use decreased in uncircumcised men
Popula%on impact of MC, Rakai Rakai Community Cohort Study (RCCS) ~14,000 persons 15-49, in 50 communities Approximately annual surveillance since 1994 Interview and sample collection (blood, genital swabs)
30 25 MC Prevalence in non-muslim Men, Rakai Cohort 25.8 20 19.1 Percent 15 10 12.3 5 5.6 6.5 7.6 Pre-Trial Trial Post- Trial 0 2002-03 2003-04 2005-06 2006-07 2008-09 2010
HIV incidence in men before (2000- mid 2004) and aker availability of MC 1.6 1.4 1.36 AdjRR = 0.78, CI 0.62-0.98, p=0.04 HIV Incidence/100py 1.2 1 0.8 0.6 0.4 0.2 0 1.05 non-muslim 0.55 0.5 Muslim Pre-MC Post-MC Preliminary evidence of a popula<on- level reduc<on of HIV incidence in non- Muslim men Average MC coverage 18.5%
MC Services in Rakai >18,000 MCs since 2007 Mainly by clinical officers using dorsal slit 1 central facility with 5 opera<ng rooms 4 satellite facili<es in rural health centers Maximum efficiency with dedicated MC teams
Age Distribu%on of Clients for Service Circumcision Rakai 2008-2011 50 45 40 Percent 35 30 25 20 15 10 <19 20-24 25-29 30-34 35-39 40-49 50_ 5 0 2008 2009 2010 2011 Increased uptake by adolescents Decrease in older men (Also seen in Kisumu and Orange Farms)
Implementa%on Science RFA 2012-15 Aim 1. To increase uptake of MC, par<cularly among higher risk men in a rural seqng by: Improved messaging/outreach Increased mobile services Task sharing and task shiking Aim 2. To conduct an acceptability/safety study of Early Infant Male Circumcision (EIMC) by non- physicians. Randomized trial of NMWs vs Clinical Officers Aim 3. To assess the popula<on prevalence of MC, es<mate the impact of MC on HIV incidence, number of MCs per infec<on averted and cost per infec<on averted, using Rakai cohort data.
Preliminary qualita%ve studies and messaging (NICHD 1R01 HD070769-01; Gates Founda<on 22006.03) Focus group discussions (FGD) and in- depth interviews (IDIs) on barriers to and facilitators of MC Male MC acceptors and non- acceptors, women and community leaders/gatekeepers Preferred messages and methods of MC informa<on and service delivery (e.g., outreach in venues where men congregate in bars, markets, transport hubs), use of sta<c or mobile clinics Messages disseminated through village opinion leaders, general community mee<ngs, drama/music groups, radio talk shows and a film/video van
Mobile MC Camps Travel <me and <me off work barriers to MC (Herman- Roloff et al Plos One 2011) Sta<c services can saturate catchment popula<ons Need to bring services to the communi<es Pilot camps >900 MCs in 15 working days Low Aes Major new program of mobile MC services
Early Infant MC (EIMC) Simpler, cheaper and safer than adolescent/adult MC Delayed impact on HIV Need task shiking to nurse- midwives (NMWs) who have contact with mothers during and aker pregnancy