HIV Prevention for Serodiscordant Couples

Introduction

  1. Definition of the Prevention Area

    HIV-serodiscordant couples, in which one partner is HIV-positive and the other is HIV-negative, are now recognized as a priority for HIV prevention interventions.

  2. Epidemiological Justification for the Prevention Area

    Although there is considerable variation across countries, recent studies of mature epidemics in sub-Saharan Africa show that up to two-thirds of couples dealing with HIV are discordant. These studies assessed the extent to which HIV transmission within marriages was spurred by high rates of HIV among heterosexual couples in sub-Saharan Africa. One analysis estimated that 55 to 92 percent of new, heterosexually acquired HIV infections among adults occurred within serodiscordant marital or cohabiting relationships. Additionally, among discordant couples, only the female partner was infected in 30 to 40 percent of cases, which contradicts the common perception that only men, not women, are the HIV-positive partner.

    According to a research review, the following factors make it more likely that a person living with HIV will transmit the virus to his or her partner: the presence of other sexually transmitted infections, particularly genital ulcerative diseases; high viral load; failure to use condoms correctly and consistently; and specific sexual practices, such as a high number of sexual partners and higher frequency of sexual contact. Concurrent sexual partnership may also contribute to risk. The risk of transmission is especially high during early infection, when the virus is estimated to be 26 times more infectious than during later stages of infection. This makes it especially important to identify HIV infection during the early, acute stage.

    Prevention responses also need to take into account the progress of the epidemic. One hypothesis is that in early epidemics, discordancy in most couples arises due to HIV infection of one partner through a pre-existing relationship, whereas in more mature epidemics, a greater proportion of HIV-negative partners initiate relationships with a new partner who is already infected.

  3. Core Programmatic Components

    HIV prevention programs among discordant couples are traditionally based on three types of interventions: 1) couples HIV testing services (HTS)—both through community-based outreach and antenatal clinics; 2) group-based workshops with serodiscordant couples; and 3) integrated antiretroviral therapy (ART) and HIV prevention programs. These programs often include risk reduction counseling, referrals to treatment, counseling on family planning, and an avenue to further care and support services.

    Couples HTS is the cornerstone of many discordant couple interventions; it remains the only way to identify couples in which one partner is HIV-positive and one is HIV-negative. New and innovative methods are being developed to increase uptake of couples HTS, since many individuals and couples do not know their status. To increase HTS uptake among couples, programs will likely need to integrate the couples testing with broader HIV programs including care, treatment, and support services; mother-to-child-transmission programs; male circumcision; condom promotion; partner reduction; and other behavior change interventions.

    Effective prevention programming is necessary for serodiscordant couples, targeted both to the couple and to the individuals. One study showed that the HIV-negative partner increased the number of their outside sexual partners after learning their partner's HIV-positive status. Campbell et al (2011) confirmed this result, showing that about 27 percent of seroconverters in serodiscordant couples in the study were infected by an outside partner.

    New advances in the biomedical field (pre-exposure prophylaxis and ART as prevention) have demonstrated success in reducing HIV transmission among discordant couples. These prevention methods are included in the World Health Organization guidelines on the use of antiretroviral drugs for treating and preventing HIV infection.

  4. Current Status of Implementation Experience

    Programs in developing countries aimed at reducing transmission of HIV in discordant couples are too new to evaluate for effectiveness. To date, interventions have largely been conducted within structured research protocols. It is still uncertain whether the efficacy of such interventions will work in real-life settings, and whether they can be scaled up to achieve sufficient reach to reduce rates of HIV transmission at the population level.

UPDATED 6/2016

What We Know

Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1-Serodiscordant Couples

Mugo, N. R., Heffron, R., Donnell, D., et al. AIDS (2011), 25(15), pp. 1887–1895.

This secondary data analysis study explored how pregnancy in serodiscordant couples affected HIV-1 acquisition in women and HIV-1 transmission from women to men. Data from 3,321 African couples in seven countries who were enrolled in the Partners in Prevention HSV/HIV Transmission Study, a study that tested the effect of acyclovir herpes simplex virus type 2 suppressive therapy for the prevention of HIV transmission, was utilized. Multivariate Cox proportional hazard analysis was performed to control for any demographic, clinical, or behavioral factors. During the study period, 151 individuals seroconverted (with 61 infections occurring among women and 90 occurring among men) and there were a total of 823 pregnancies. Couples who became pregnant were younger and more likely to report unprotected sex during pregnancy. About 28 percent of women who HIV-1 seroconverted during the study were pregnant. The incidence of HIV-1 during pregnancy was 7.35 per 100 person-years compared to 3.01 per 100 person-years during nonpregnancy, but was not found to be statistically significant in multivariate analysis. About 21 percent of men who HIV-1 seroconverted during the study period did so while their partner was pregnant. The incidence of female-to-male HIV-1 transmission was 3.46 per 100 person-years during pregnancy compared to 1.58 per 100 person-years when the partner was not pregnant, and was statistically significant after multivariate analysis. In conclusion, there is an increased risk of HIV acquisition among HIV-negative women and increased risk of HIV transmission to men during pregnancy, which calls for more emphasis on risk reduction counseling, family planning, and early initiation of antiretroviral therapy during pregnancy among discordant couples.

Condom Effectiveness in Reducing Heterosexual HIV Transmission: A Systematic Review And Meta-Analysis Of Studies On HIV Serodiscordant Couples

Giannou, F.K., Tsiara, C.G., Nikolopoulos, G.K. Expert Review of Pharmacoeconomics & Outcomes Research (October 2015), 21: 1–11.

This systematic review and meta-analysis reassessed the effectiveness of condoms in reducing heterosexual transmission of HIV in light of new evidence from studies on serodiscordant couples since the previous review in 2000. The authors found 25 eligible studies that included a total of 10,676 HIV-serodiscordant heterosexual couples. The risk of HIV transmission was associated with use, and was considerably lower among couples who always used condoms compared to those who never used condoms or used them inconsistently. HIV-negative consistent condom users were 71–77 percent less likely than those who never or sometimes used condoms to acquire HIV following repeated sexual encounters with an HIV-positive partner. The protective effect was slightly higher when the man, rather than the woman, was HIV-positive. Effectiveness also varied across regions, and was very high (adjusted 87%) in Asia, especially China. The authors noted that most recent studies attempted to control for confounding. Social desirability bias, associated with self-report on condom use, sexual behavior, and other sensitive topics, may explain the incomplete condom protection observed. Future studies should seek to use methods that can generate unbiased and more precise estimates of condom use; and to examine social, cultural, and biological differences to inform projection modelers and policymakers.

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Cohen, M.S., Chen, Y. Q., McCauley, M., et al. New England Journal of Medicine (2011), 365(6), pp. 493–505.

This article reports expanded demographic and clinical information from the HIV Prevention Trials Network 052 trial, whose interim findings, released on April 28, revealed a 96 percent reduction in the risk of HIV transmission among participants with a CD4 count between 350 and 550 cells per cubic millimeter (cells/mm³) who received antiretroviral therapy (ART) immediately upon entering the trial. Over half of the participating serodiscordant couples (54 percent, or 954 couples) came from Africa, 531 couples from Asia, and 278 couples from the Americas; 50 percent of the infected partners were men. Enrollees were randomized to receive ART immediately upon testing positive or to delay therapy until their CD4 counts dropped below 250 cells/mm³ or they acquired an AIDS-related illness. Of the total of 39 HIV transmission events, 35 occurred among participants in the delayed arm (with 82 percent occurring among African couples). A total of 61 percent of the 28 “linked” events (in which HIV transmission was directly linked to the infected study partner) occurred among individuals whose partner had a CD4 count greater than 350 cells/mm³, and 64 percent of the HIV transmissions were from female to male partners. Individuals in the immediate treatment arm experienced a 41 percent lower risk of experiencing a clinical event, such as tuberculosis, compared to those in the delayed arm. According to the authors, the most likely mechanism in preventing HIV-1 transmission was sustained suppression of HIV-1 in genital secretions—the result of ART. The authors found that early initiation of ART has clinical benefits for both HIV-1–infected individuals and their uninfected partners, and therefore must be rolled out as a prevention strategy to reduce the spread of HIV-1 infection.

Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women

Baeten, J.M., Donnell, D., Ndase, P., et al. New England Journal of Medicine (August 2012), 367(5):399–410.

This article reported on the Partners PrEP Study, a randomized trial assessing oral antiretroviral drugs for use as pre-exposure prophylaxis (PrEP). The study followed 4,747 HIV-1-serodiscordant heterosexual couples from Kenya and Uganda for up to 36 months. At enrollment, the HIV-1 seropositive participants were not eligible for antiretroviral treatment based on national guidelines. The HIV-1-seronegative partner was randomly assigned to one of three once-daily products: 1,584 to tenofovir (TDF); 1,579 to combination tenofovir-emtricitabine (TDF-FTC); and 1,584 to placebo. Participants were followed monthly, and received a comprehensive HIV prevention package. Both active products significantly reduced the risk of HIV-1 infection compared with placebo. The placebo was discontinued, and data reported early, after the data safety and monitoring board noted a strong trend toward protection in both active arms. A total of 82 HIV-1 infections occurred during the study: 17 in the TDF group (0.65 per 100 person-years), 13 in the TDF-FTC group (0.50 per 100 person-years), and 52 in the placebo group (1.99 per 100 person-years). Reductions in HIV-1 incidence were similar in the active arms (67% with TDF and 75% with TDF-FTC). Efficacy differed slightly among women (71% for TDF and 66% for TDF-FTC) and men (65% for TDF and 84% for TDF-FTC). This study provided proof of concept that oral TDF and TDF-FTC both prevent HIV-1 infection in heterosexual men and women.

HIV-1 Transmission among HIV-1 Discordant Couples Before and After the Introduction of Antiretroviral Therapy

Reynolds, S., Makumbi, F., Nakigozi, G., et al. AIDS (2011), 25(4), pp. 473–477.

The observational cohort study examined the relationship between HIV-1 seroconversion before and after antiretroviral therapy (ART). Discordant couples were identified through the annual Rakai Community Cohort study and used data from 2004 to 2009 surveys. In 2004, all HIV-positive Rakai residents were offered free ART if their CD4 counts were at or below 250 cells/mL or were at stage IV disease as defined by the World Health Organization. HIV incidence and risk behaviors of the uninfected partners were retrospectively compared with when their partner started ART. During the 2004 to 2009 time period, 250 discordant couples were identified, of whom 32 met the criteria for initiation of ART. In 58 percent of the couples, the male was the HIV-positive index partner. It was found that before the initiation of ART, the transmission rate was 9.2/100 person-years (95 percent confidence interval, 6.59–12.36). There were no HIV-1 transmissions among the couples who started ART. There were no statistically significant differences between the two groups (ART versus non-ART). Consistent condom use with any partner increased from about 14 percent prior to ART compared to about 54 percent after ART and was statistically significant. Viral loads were found to be high. At 6 months, the majority (71.4%) had viral loads below 400 copies/mL. The reduced HIV-1 transmission levels among discordant couples most likely were due to the reduced viral loads of the HIV-positive partner.

Viral Linkage in HIV-1 Seroconverters and Their Partners in an HIV-1 Prevention Clinical Trial

Campbell, M.S., Mullins, J.I., Hughes, J.P. et al. PLOS One (2011), 6(3), p. e16986.

The study linked the HIV-1 strains within HIV discordant couples when the uninfected partner seroconverted to determine if the infection could be epidemiologically connected to the infected partner. The data was from the Partners in Prevention HSV-2/HIV-1 Transmission Study that enrolled HIV serodiscordant couples from several African countries. A total of 3,408 discordant couples were enrolled in the study, and 155 seroconverted to HIV during the course of the trial identified through HIV-1 serology at site. A total of 151 were confirmed by a positive HIV-1 Western bolt test and included in the analysis. The majority (71.5%) of transmissions were linked to the infected partner, 26.5 percent were not linked to the infected partner, and 2 percent could not be determined. Seroconverters were most likely female, had a shorter average time to seroconversion than unlinked pairs (6 months versus 12 months after enrollment), and were identified within the first 3 months of the study visit compared to after 3 months. Reporting sexual activity with the infected partner was higher among those who had linked cases. Unlinked cases reported increased sexual activity with outside partners compared to linked cases, and these unlinked cases were more likely male. It was also found that the HIV-positive partner had higher baseline plasma HIV-1 RNA levels in linked cases versus unlinked cases. The results of the study underscore the necessity of HIV prevention interventions targeted toward serodiscordant couples, and messages should be uniquely tailored to gender and HIV-1 status characteristics.

Antiretroviral Therapy for Prevention of HIV Transmission in HIV-Discordant Couples

Anglemyer, A., Rutherford, G.W., Horvath, T. et al. Cochrane Database of Systematic Reviews (April 2013), 4(No. CD009153), doi:10.1002/14651858.CD009153.pub3.

This systematic review assessed whether antiretroviral therapy (ART) use is associated with decreased risk of HIV transmission from an HIV-positive to an HIV-negative sexual partner. The review also examined whether ART in a patient with a CD4 count of ≥350 is associated with a lower risk of HIV transmission. A search of studies on HIV-discordant couples (which included heterosexual or homosexual couples) yielded 10 eligible studies (one randomized controlled trial or RCT and nine observational studies). ART was associated with decreased risk of HIV transmission in serodiscordant couples, and this association was especially strong in the large RCT. Several observational studies also showed independent effects of ART. One observational study showed a non-significant increase in risk, and a later study showed no difference. Few studies stratified their data based on CD4 counts, but the large RCT showed benefits among index partners with CD4 counts between 350 and 550. The studies did not assess the durability of protection, the balance of benefits and risks, long-term adherence, or the feasibility of implementation. The authors concluded that ART can be an important HIV prevention approach in serodiscordant couples.

Advances in HIV Prevention for Serodiscordant Couples

Muessig, K.E. and Cohen, M.S. Current HIV/AIDS Reports (December 2014), 11(4): 434–446.

This review summarized biobehavioral and biomedical HIV prevention options for serodiscordant couples, focusing on advances achieved in 2013 and 2014. The World Health Organization issued guidelines in 2012 that recommend couples HIV testing services (CHTS), support for mutual disclosure of HIV status, antiretroviral therapy (ART) initiation, and pre-exposure prophylaxis (PrEP). Benefits of CHTS include lower risks of HIV transmission and unplanned pregnancy, and increasing condom use and access to reproductive health services. Couples interventions aimed at communication, negotiation, and risk reduction are also beneficial. CHTS should also be offered to men who have sex with men (MSM). Medical male circumcision is recommended within heterosexual couples with HIV-negative males. Early treatment and ART can reduce HIV transmission up to 96 percent; ensuring that treatment as prevention (TasP) is operational and effective in clinical and community settings is critical. Oral PrEP is effective; the U.S. Centers for Disease Control and Prevention issued clinical practice guidelines for PrEP for sexually active MSM, people who use injecting drugs, and heterosexual men and women. PrEP alone or in combination with TasP can help reduce HIV risk during conception and pregnancy; research is needed to develop optimal protocols. With new ART-based prevention, the authors recommended further research to determine how best to deliver and scale up behavioral and biomedical interventions in combination, how to make them available to MSM, and how to ensure adherence for optimal impact.

Putting it Into Practice

Effect of Couples Counselling on Reported HIV Risk Behavior among HIV Serodiscordant Couples by ART Use, HIV Status and Gender in Rural Uganda

King, R., Min, J., Birungi, J. et al., PLOS ONE (September 2015),10(9): e0136531.

This study examined self-reported HIV risk behavior to determine whether a couples counseling intervention for heterosexual HIV-discordant couples in Uganda was associated with behavior change. The study enrolled 586 participants in a larger study examining the effectiveness of treatment as prevention. Participants received quarterly couples counseling in risk reduction, regular condom use, and HIV transmission risk. Findings were assessed according to three categories of couples, where the HIV-positive partner: received antiretroviral therapy (ART) before enrollment; started ART during the study; and never received ART. Responses at baseline and 6-, 12-, 18-, and 24-month follow-up showed increases in reported condom use with primary partners over time. Men reported fewer concurrent partners, more knowledge of partners’ HIV serostatus, and a trend towards improved condom use with non-primary partners. Concurrency among women did not diminish, but incidence was low (1.3% throughout the study). The authors noted that standard couples counseling may have different and possibly larger effects in the general population, since couples in this cohort were already aware of their partners’ serostatus. Condom use was already quite high at baseline, likely due to existing interventions for HIV-positive people. The authors concluded that routine counseling for serodiscordant couples should be integrated into ART programs.

Studies of Assisted Reproduction Techniques (ART) for HIV-1-Discordant Couples Using Washed Sperm and the Nested PCR Method: A Comparison of the Pregnancy Rates in HIV-1-Discordant Couples and Control Couples

Kashima, K., Takakuwa, K., Suzuki, M., et al., Japanese Journal of Infectious Diseases (May 2009), 62(3): 173–176.

This study examined the efficacy and safety of sperm washing and nested polymerase chain reaction (PCR) assay techniques to eliminate HIV-1 from the sperm of serodiscordant couples who want to conceive. Sperm washing has not been proven to completely remove HIV-1 RNA, and exposure to sperm during intrauterine insemination may pose risks for HIV transmission to women. The authors evaluated sperm washing and nested PCR assays in 27 serodiscordant heterosexual couples with HIV-positive men. In these couples, they separated motile spermatozoa, and used a PCR assay to check HIV-1 RNA and proviral DNA (DNA that can enter cells and replicate) before fertilization via intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) and before embryo transfer. No HIV-1 RNA or proviral DNA were detected by the nested-PCR assay in any of the spermatozoa samples. They compared the clinical outcomes to control couples, who underwent ICSI and IVF for infertility. Pregnancy rates were significantly higher in the intervention than in the control couples. All women and babies remained HIV-1 negative throughout the study. The authors suggested that sperm washing and nested PCR could help serodiscordant couples to conceive more safely and effectively, and urged larger studies on the technique’s safety and efficacy.

Gendered Differences in the Perceived Risks and Benefits of Oral PrEP Among HIV-Serodiscordant Couples in Kenya

Carroll, J.J., Ngure, K., Heffron, R., et al., AIDS Care (January 2016), 11: 1–7, doi: 10.1080/09540121.2015.1131972.

This qualitative study explored sociocultural factors that affect adherence to oral pre-exposure prophylaxis (PrEP). The authors conducted in-depth interviews and focus groups with 68 individuals from 34 serodiscordant couples who had participated in the Partners PrEP Study in Thika, Kenya. They found high adherence to PrEP, and conflicting interests connected to traditional gender roles. Three key factors shaped perceptions of PrEP: gendered power dynamics and control over household decision-making; conflicts between risk-reduction strategies and male sexual desire; and cultural definitions of women's work. Power dynamics placed health care decisionmaking within men’s purview, while gendered definitions of labor left women to manage day-to-day aspects of health care. Therefore, PrEP use by either spouse would likely increase women’s labor. HIV-positive men generally made decisions for themselves and their spouses, while HIV-negative men viewed it as a shared responsibility. Men saw pill-taking as a burden, even when they took their pills regularly. Men’s desire for sexual pleasure may conflict with behavior change needed to reduce risk of HIV acquisition. HIV-positive women reported that their partners often refused condoms and engaged in outside sex. Delivering PrEP in communities, the authors concluded, will require programs that incorporate understanding of key social factors, especially gender and couple dynamics around HIV serostatus, and broader gender roles.

Outside Sexual Partnerships and Risk of HIV Acquisition for HIV Uninfected Partners in African HIV Serodiscordant Partnerships

Ndase, P., Celum, C., Thomas, K., et al. Journal of Acquired Immune Deficiency Syndromes (2012), 59(1), pp. 65–71.

A prospective study was conducted to measure the sexual behaviors of HIV-negative individuals in serodiscordant couples. Data was from the Partners in Prevention HSV/HIV Transmission study that was carried out from 2004 to 2008 in seven African countries. The HIV-negative partners completed an interviewer-administered questionnaire on sexual behavior at enrollment and every quarter. Blood samples were also collected to genetically link the HIV subtypes of the HIV-positive partner to the newly infected partner. A total of 3,381 serodiscordant couples were enrolled in the study. Over the two years of follow-up, the number of outside partners among the uninfected individuals in the couple increased from 3.1 percent to 13.9 percent. Those who reported sex with their HIV-positive partner in the month prior to the questionnaire were less likely to have an outside partner. Uninfected partners reported less sexual activity with their infected partner during the two-year follow-up period (73.2% to 93.5%). There was also an increase of the uninfected partner reporting no sexual activity with the infected partner and an increase of sexual activity with an outside partner during the follow-up period. Condom use was more common among outside partners than with the HIV-positive partner. Of those who HIV seroconverted during the study and reported to have an outside partner, most (86%) had an HIV subtype that was distinct from their HIV-positive partner, which indicates that they did not acquire HIV from their primary relationship. Risk-reduction measures adopted by the HIV-negative partner should be taken into account when counseling serodiscordant couples.

What’s Love Got to Do With It? Explaining Adherence to Oral Antiretroviral Pre-Exposure Prophylaxis for HIV-Serodiscordant Couples

Ware, N.C., Wyatt, M.A., Haberer, J.E., et al. Journal of Acquired Immune Deficiency Syndromes (2012), 59(5), pp. 463–468.

A qualitative study was conducted to identify influences on adherence to pre-exposure prophylaxis (PrEP) from both the HIV-negative partner and -positive partner in serodiscordant couples. Participants who were enrolled in the Partners PrEP study and were from the Kabwohe Clinical Research Centre in rural Uganda were sampled for this study. Forty-five PrEP participants and fifteen of their partners were interviewed. Mean duration of the partnership was 9.8 years, and 80 percent of the couples had children. It was found that there was a dilemma between wanting to continue the relationship but fearing infection, loss of health, and early death when learning of their discordant status. PrEP offered many a means for hope and opportunity in being able to maintain the relationship while staying uninfected. In other couples, tension and anger still persisted after PrEP use, and adherence suffered. The results of the qualitative study suggest that the strength of the relationship has a direct effect on adherence. Participants also preferred to use PrEP over condoms as an HIV prevention method. It is important to understand why couples want to stay together in supporting PrEP adherence.

Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modeling Study

Hallett, T.B., Baeten, J.M., Heffron, R., et al. PLoS Medicine (2011), 8(11), p. e1001123.

The paper describes a modeling study that tested various scenarios on the effectiveness of early initiation of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) for prevention within HIV serodiscordant couples. The model used data from three sites in South Africa that participated in the Partners in Prevention HSV/HIV Transmission Study as well as results from the specific clinical trials on PrEP and ART for prevention. Three analyses were performed: 1) four different PrEP implementation strategies, 2) starting PrEP then discontinuing use when the infected partner begins ART compared to early ART but no PrEP, and 3) various models were tested to determine the optimal combination of PrEP and ART, and cost and efficiency were reviewed as well. It was found that PrEP use at all times, whether or not the infected partner was taking ART, was the most effective out of the four scenarios in reducing transmission. For the second analysis, it was found that both scenarios increased costs and reduced infections. For the third analysis, when PrEP and ART were available, it would be most effective for higher-risk couples to offer PrEP to the uninfected partner before the infected partner started ART. For lower-risk couples, early initiation of ART would be the most cost-effective. In conclusion, PrEP and ART could be reliable combination prevention strategies to reduce transmission and acquisition for serodiscordant couples.

Cost-Effectiveness of Pre-Exposure Prophylaxis Targeted to High-Risk Serodiscordant Couples as a Bridge to Sustained ART Use in Kampala, Uganda

Ying, R., Sharma, M., and Heffron, R. Journal of the International AIDS Society (July 2015), 18(Supplement 3): 20013, doi: 10.7448/IAS.18.4.20013, eCollection 2015.

This modeling study evaluated the cost-effectiveness of implementing time-limited pre-exposure prophylaxis (PrEP) to prevent HIV acquisition in serodiscordant couples. PrEP would serve as a short-term “bridge” during the first six months of antiretroviral therapy (ART) for the HIV-positive partner until he or she is virally suppressed and at low risk of transmitting HIV. The authors modeled the health and economic impacts of this bridge strategy versus increasing ART coverage to 55 percent of HIV-positive persons with a CD4 count of ≤500 (without PrEP) in terms of cost effectiveness, infections averted, and disability-adjusted life years (DALYs). Adding a PrEP bridging intervention until ART initiation to the existing Ugandan standard of care was cost-effective for averting HIV infections in generalized HIV epidemic settings. For averting HIV infections, implementing a PrEP and ART program for high-risk serodiscordant couples was very cost-effective. However, increasing ART coverage to 55 percent of HIV-positive persons with a CD4 count of 500 or below without implementing PrEP, was not cost-effective. When the outcome is DALYs, increased ART coverage was most cost-effective due to the immediate impact of treatment on DALYs. The authors concluded that PrEP and ART for high-risk persons have the potential for synergy and are cost-effective in preventing HIV infections in high-prevalence settings.

Association Between Male Circumcision and Incidence of Syphilis in Men and Women: A Prospective Study in HIV-1 Serodiscordant Heterosexual African Couples

Pintye, J., Baeten, J.M., Manhart, L.E., et al. Lancet Global Health (November 2014), 2(11): e664–671.

This large, prospective cohort study examined the association between male circumcision and incident syphilis in HIV-positive and -negative African men and their female sexual partners. Study participants comprised 4,716 HIV-1 serodiscordant heterosexual couples enrolled in the Partners PrEP [pre-exposure prophylaxis] Study in Uganda and Kenya. Participants were enrolled in the study for up to 36 months, and were tested for syphilis and assessed for male circumcision status annually. The analysis for this study included all couples with known male circumcision status. At enrollment, syphilis prevalence was lower in circumcised men with and without HIV than in uncircumcised men, a pattern also seen in their female partners. During the study, 221 incident syphilis infections were reported. Male circumcision was associated with a 42 percent reduction in incident syphilis in men (62% in men with HIV; non-significant in men without HIV). Among women, men's circumcision was associated with a 59 percent reduction in incident syphilis (48% in women with HIV; 75% in women without HIV). Male circumcision was associated with reduced prevalence and incidence of syphilis for men and women, suggesting that medical male circumcision could substantially reduce incidence of syphilis and its consequences. The authors recommended communicating this additional benefit during circumcision programs, and conducting additional studies to confirm these findings in other populations.

Behavioural Interventions for HIV Positive Prevention in Developing Countries: A Systematic Review and Meta-Analysis

Kennedy, C.E., Medley, A.M., Sweat, M.D., O’Reilly, K.R. Bulletin of the World Health Organization (August 2010),88(8): 615–623.

The review explored the efficacy of prevention programs for people infected with HIV in the developing world setting, and examined whether interventions targeting both HIV-positive and -negative individuals have varying effectiveness. Eighteen articles met the criteria for inclusion. Most (15 studies) were conducted in sub-Saharan Africa, were in clinical settings (14 studies), and included heterosexual populations (12 studies). Nine studies targeted both HIV-positive and HIV-negative individuals and stratified the results by target population. These nine studies were within HIV counseling and testing interventions. Ten studies evaluated behavioral interventions targeted to HIV-positive individuals. Five studies were with serodiscordant couples. When comparing behavioral interventions targeting HIV-negative and -positive individuals, it was found that condom use statistically increased among positive individuals but was not statistically significant among negative individuals. Interventions targeting serodiscordant couples increased condom use significantly. There was also a modest positive effect on reducing multiple sexual partners in behavioral interventions targeted to HIV-positive adults, and an increase in disclosing one’s HIV-positive status. These results, the authors said, demonstrated the positive effect on behavioral outcomes from prevention interventions. They concluded that prevention interventions should be expanded among HIV-positive individuals and serodiscordant couples.

Risk Reduction Among HIV-Seroconcordant and -Discordant Couples: The Zambia NOW2 Intervention

Jones, D., Kashy, D., Chitalu, N. AIDS Patient Care and STDS (August 2014), 28(8): 433–441.

This study compared intervention approaches, assessing whether an HIV risk reduction intervention would increase condom acceptability and decrease risk behavior when delivered to couples in groups (divided by sex) or to individual couples. It also examined the impact of couple members’ influence on acceptability of sexual barrier methods (male and female condoms, and a gel and cream), and assessed whether product acceptability, intimate partner violence (IPV), and/or partner communication predicted sexual barrier use. HIV-positive seroconcordant (n=194) and serodiscordant couples (n=22) were recruited in Lusaka, Zambia, and randomized to either the group- or couple-based intervention. The interventions in both arms consisted of four sessions on sexual risk reduction, consistent use of male and female condoms, reducing sexual risks from alcohol or substance use, communication and conflict resolution, and adherence to treatment. Participants were assessed at baseline, 6, and 12 months using an audio computer-assisted self-interview. Self-reported willingness to use barriers, acceptability, and barrier use and positive communication increased over time in both interventions; reported IPV decreased. Couple and group sessions achieved similar increases in reported sexual barrier use following the intervention. These findings, the authors said, highlighted the mutual influence of partners and product acceptability as predictors of sexual barrier use among couples. They urged consideration of both these factors during future interventions to achieve optimal outcomes in sexual risk behavior.

Challenges With Couples, Serodiscordance and HIV Disclosure: Healthcare Provider Perspectives on Delivering Safer Conception Services for HIV-Affected Couples, South Africa

Crankshaw. T.L., Mindry, D., Munthree, C. et al. 2014 Journal of the International AIDS Society (March 2014), 17, doi: 10.7448/IAS.17.1.18832, eCollection 2014.

This qualitative study explored health care providers' viewpoints and experiences regarding safer conception care for serodiscordant couples. The authors conducted in-depth interviews and focus group discussions with 25 doctors, nurses, and lay counselors at urban and rural antiretroviral therapy clinics in Durban, South Africa. Providers often felt unprepared to manage clinical and relationship considerations in serodiscordant couples who wish to conceive—especially the clinical implications of serodiscordance in couples, HIV disclosure, and HIV testing and clinical care for men. Providers did not always feel prepared to help clients with disclosure and its associated risks, including abandonment and violence. They also reported practical and ethical dilemmas: balancing their professional priorities (minimizing risk to the HIV-negative partner) while supporting a client’s or couple’s desire to become pregnant. Many were concerned about deviating from clear messages on consistent condom use, even for a short time. Participants agreed that ideally, counseling and clinical care around conception involves both partners, but drawing male partners into care can be difficult. Few were familiar with 2011 guidelines on safer conception, and they expressed interest in such guidelines and in being trained in their use. The authors concluded that specific training on ethical issues and couple counseling, including disclosure, should be part of safer disclosure programs.

A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy

Heffron, R., Cohen, C.R., Ngure, K., et al. PLOS ONE (December 2015), 10(12): e0145515.

This article described the development and validation of a pregnancy prediction scoring tool to identify serodiscordant couples who are more likely to become pregnant within the next year. Such a tool could help identify couples for counseling on contraceptive use or safer conception to minimize risk of HIV transmission. The authors developed and validated the tool using datasets on nearly 7,000 couples who participated in HIV prevention and service delivery trials in Kenya and Uganda. They used standardized clinical prediction methods limited to variables routinely collected at an initial clinic visit. Five factors emerged to include in the tool: the woman’s age, the number of her living children, duration of the partnership (measured by time since first sex), any unprotected (condomless) sex in the past month, and non-use of an effective contraceptive (oral, IUD, implant, injectable, diaphragm, or surgical). A score ≥7 effectively identified a subset of each study population most likely to become pregnant, and a significant majority of the pregnancies occurred in this subset of women. The authors said that this tool could be used effectively in research and clinical settings to engage serodiscordant couples in counseling about their reproductive goals and offer appropriate services for safer conception or contraception.

Tools and Curricula

Guidance on Oral Pre-Exposure Prophylaxis (PrEP) for Serodiscordant Couples, Men and Transgender Women Who Have Sex with Men at High Risk of HIV: Recommendations for Use in the Context of Demonstration Projects

World Health Organization (2012).

PrEP clinical trials have been successful in two populations--men and transgender women who have sex with men (MSM-TG) and serodiscordant heterosexual couples. However, translating these results to real world settings is less known. WHO recommends that countries implement demonstration projects that will offer advice on key safety, effectiveness, adherence, and sustainability questions surrounding PrEP interventions. The guidance provides an overview of the research conducted to date and recommendations on PrEP for serodiscordant couples, MSM-TG, and other groups. The guidance lists nine key points to guide demonstration projects including assuring the HIV-negative status of participants, monitoring the safely of participants, supporting high levels of adherence, and developing transition mechanism for those who want/need to discontinue treatment. It is planned that WHO will review and revise its guidance in 2015.

HIV Prevention for Serodiscordant Couples: Technical Brief

Spino, A., Clark, M., & Stash, S. 2010. AIDSTAR-One.

The technical brief provides an overview of the research on HIV prevention for serodiscordant couples including an introduction on the epidemiological significance in targeting this population and key prevention interventions. There are three broad categories of prevention interventions among discordant couples: couples HIV counseling and testing, group-based interventions, and a supportive environment. Several successful programs are highlighted through the document. The challenges and barriers to implementing prevention programs for serodiscordant couples are listed, and their solutions are discussed. These include how to involve the partners in the intervention, gender imbalances, increasing knowledge about what it means to be discordant, and guaranteeing that the quality of interventions is high. Clear messages are outlined such as stating that HIV discordance is common, couples can remain discordant for a long time, discordance does not necessarily mean the partner is unfaithful, no one is immune to HIV, the HIV-negative partner is at high risk of HIV, and effective risk reduction options do exist. Four common questions that are pertinent to implementation are asked and answered in the brief. Additional resources are provided.

Additional Resources

Debate Three: Discordant Couples and HIV Transmission

The World Bank and the U.S. Agency for International Development. 2010.

The co-sponsored World Bank and U.S. Agency for International Development debate was centered around the statement: “Intracouple HIV transmission between couples in long term stable partnerships drive a majority of HIV transmission and should receive the majority of HIV prevention funding.” Two experts argued for and two argued against the statement. The summary report can be found at the site as well as additional materials including the program, supplemental information, flyer for the debate, and links to various pages on the AIDSTAR-One Prevention Knowledge Base. Viewers can also watch the debate in four parts through the website.