1. Caitlin E. Kennedy 1, Kevin Armstrong 2, Virginia A. Fonner 1, Michael D. Sweat 2, Kevin R. O’Reilly 2 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 2 The Medical University of South Carolina, Charleston, SC, USA Is use of antiretroviral treatment associated with decreased condom use? A meta-analysis of studies from low- and middle-income countries

2. Background Rapidly expanding ART access in low- and middle-income countries (LMICs) ART may be associated with decreased condom use due to:  physical health improvements  treatment optimism  assumptions of non-infectiousness with low/undetectable viral load, etc. Conversely, ART may be associated with increased condom use due to:  reduced depression  increased hope for the future  regular medical contact and counseling, etc. Research from high-income countries has shown no association between ART use and unsafe sex (Crepaz et al., 2004) Despite a rapidly expanding evidence base, no published meta- analyses have examined this issue in LMICs

3. Objective To conduct a systematic review and meta-analysis of the association between ART and condom use among PLHIV in LMICs Part of the Evidence Project – NIMH-funded project examining the strength of evidence for different HIV-related behavioral interventions in LMICs Follow PRISMA guidelines for all systematic reviews

4. Inclusion criteria Published in peer-reviewed journal between Jan 1, 1990 – May 9, 2012 Conducted in LMIC as defined by the World Bank Provided clinical care/ART to people living with HIV Presents pre/post or multi-arm data comparing individuals on ART to those not on ART on one of the following sexual risk behavior outcomes:  Condom use, number of sexual partners, types of sexual partners (e.g. extramarital sex), abstinence/sexual activity, sexual initiation, sexually transmitted infections (STIs)

5. Search strategy Electronic database search  5 databases: PubMed, EMBASE, PsycINFO, Sociological Abstracts, and CINAHL  Search terms: (“ARV treatment” OR “opportunistic infection” OR “medical treatment” or ART or ARV or HAART or “clinical care” or “medical intervention” OR “medical care”) AND (behaviour or behavior) AND HIV Hand searching the table of contents of key journals  AIDS, AIDS and Behavior, AIDS Care, and AIDS Education and Prevention Screening reference lists of included studies

6. Data extraction and analysis Two graduate student trained coders independently abstracted data using standardized forms Meta-analysis conducted for outcomes with a sufficient number of studies  Comprehensive Meta-Analysis software  Random effects models  Used adjusted odds ratios where possible  Stratified by gender and partner type where possible

7. Search results 6646 initial citations 37 studies met inclusion criteria 15 studies were included in meta- analysis for condom use outcomes Records identified through database searching (N=7588) Additional records identified through other sources (N=8) Records screened (N=6646) Records after duplicates removed (N=6646) Full-text articles assessed for eligibility (N=99) Records excluded (N=6547) Articles included in review (N=37) Full-text articles excluded (N=62) because: Took place in a developed country (n=12) Did not contain pre/post or multi-arm results (N=9) Did not contain relevant outcomes (10) Coded as background (N=31) Articles included in meta- analysis (N=15)

8. Study descriptions Most studies from sub-Saharan Africa (N=30)  Additional studies from Thailand (N=4), Brazil (N=2), and India (N=1) Most studies used cross-sectional or prospective cohort designs  However, 2 retrospective cohorts and 5 non-randomized controlled studies (both ART and non-ART groups followed over time)

9. Meta-analysis: Consistent condom use Partner typeParticipants No. of studies Odds ratio 95% CIp-value Heterogeneity (Q test, I 2 if >2 studies) Any partner*Both genders51.41.0, 2.10.0450.080, 51.9% Males22.01.2, 3.20.004 Females41.51.3, 1.7< 0.0000.891, 0% Spouse/regular partnerBoth genders**22.61.2, 5.70.013 HIV-/unknown partners Both genders**42.61.8, 3.7< 0.0000.818, 0% Casual clients of sex workers Females (FSWs)21.51.0, 2.10.033 All partner types combined (all of the above) Both genders81.81.4, 2.5< 0.0000.005, 65.4% Males22.01.2, 3.20.004 Females61.51.3, 1.7< 0.0000.969, 0% *Includes studies that reported consistent condom use with any partner, with the most recent partner, or where the partner type was not reported **Studies did not stratify results by gender of participants Odds ratio remained largely the same when one study that combined HIV-/unknown partners with casual partners was added to this analysis: OR: 2.3, 95% CI (1.7, 3.0) p < 0.000

10. Meta-analysis: Condom use at last sex Partner typeParticipants No. of studies Odds ratio 95% CIp-value Heterogeneity (Q test, I 2 if >2 studies) Any partner*Both genders32.10.9, 4.80.101< 0.000, 93.6% Males21.81.1, 2.90.019 Females22.10.5, 8.80.305 Spouse/regular partnerBoth genders**41.61.0, 2.60.0450.003, 78.8% HIV-/unknown partnersBoth genders**32.21.0, 5.20.062< 0.000, 87.9% All partner types combined (all of the above) Both genders82.31.5, 3.6< 0.000< 0.000, 88.6% Males21.40.9, 2.10.156 Females22.10.5, 8.60.291 *Includes studies that reported consistent condom use with any partner, with the most recent partner, or where the partner type was not reported **Only one study in each of these analyses (Eisele et al., 2008) stratified results by gender of participants.

11. Summary of meta-analytic results PLHIV on ART were more likely to report consistent condom use and condom use at last sex than those not on ART  Consistent condom use: OR: 1.8 (95% CI: 1.4-2.5)  Condom use at last sex: OR: 2.3 (95% CI: 1.5-3.6) This finding was strikingly consistent across sub-analyses by gender and partner type  OR range: 1.4-2.6, although not always statistically significant The strongest effects were seen in consistent condom use with:  HIV-/unknown status partners: OR:2.6 (95% CI: 1.8-3.7)  Spouses: OR:2.6 (95% CI:1.2-5.7) Heterogeneity across analyses was generally high

12. Limitations and next steps Limitations  Generally weak study designs  Ethical limitations on RCTs  We used adjusted odds ratios where possible, although impossible to know if adjustment for confounding was appropriate  Analysis focused only on PLHIV Strengths  Large number of studies with consistent findings Currently updating search through June, 2014  >50 articles!  Will be able to meta-analyze additional outcomes such as number of partners and STIs

13. Conclusions Meta-analytic results show that in LMICs, PLHIV on ART are more likely to report condom use than those not on ART Disputes concerns about “treatment optimism” among PLHIV in care Encouraging news for continued expansion of ART programs in LMICs Suggests that “treatment as prevention” may be true in more ways than one

14. Acknowledgments This research was supported by the US National Institute of Mental Health (NIMH), grant number 1R01MH090173 We thank the following Johns Hopkins students for their screening and coding work on this review:  Morgan Philbin, Andrea Wirtz, Sarah Heidt, Ester Lei, Taylor Whitten, Lindsay Litwin, Canada Parrish, Swathi Manchikanti, Victoria Ryan, Jenny Tighe, April Monroe, Sarah Robbins, and Isabelle Feldhaus