Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Curr HIV/AIDS Rep. Author manuscript; available in PMC 2015 December 1.
Published in final edited form as:
PMCID: PMC4267973

Advances in HIV Prevention for Serodiscordant Couples


Serodiscordant couples play an important role in maintaining the global HIV epidemic. This review summarizes biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014, including World Health Organization guidelines and best-evidence for couples counseling, couples-based interventions, and the use of antiviral agents for prevention. In the past few years marked advances have been made in HIV prevention for serodiscordant couples and numerous ongoing studies are continuously expanding HIV prevention tools, especially in the area of pre-exposure prophylaxis. Uptake and adherence to antiviral therapy remains a key challenge. Additional research is needed to develop evidence-based interventions for couples, and especially for male-male couples. Randomized trials have demonstrated the prevention benefits of antiretroviral-based approaches among serodiscordant couples; however, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention.

Keywords: treatment as prevention, TasP, pre-exposure prophylaxis, PrEP, PEP, serodiscordant, HIV, AIDS, couples, prevention


I. What is a serodiscordant couple?

The term “serodiscordant couple” refers to an intimate partnership in which one person is HIV-positive and the other is HIV-negative. In research studies, the “couple” relationship is typically defined by marital, cohabitating or co-parenting status or by length of relationship (e.g. minimum of 3-6 months), intention to stay together, or reporting a certain minimum number of sexual acts with this partner within a given timeframe [1]. A number of considerations exist for research and prevention among serodiscordant couples. In general, the couple does not stay discordant forever. By definition, the HIV-negative partner is considered as “exposed and uninfected”. Indeed, trying to understand the basis for apparent protection from HIV has been the source of much investigation [2]. In addition, “stable couples” are more fluid than the definition belies: they may temporarily or permanently dissolve, reunite, or involve outside others (i.e. concurrent sexual relationships by one or both of the partners). Furthermore, couples themselves interpret serodiscordance differently in different cultural or relationship contexts [3]. For example, couples interviewed in Uganda understood serodiscordance to mean undetected infection or HIV immunity among the HIV-negative partner [4].

Serodiscordant couples play a role in maintaining the global HIV epidemic. In surveillance studies, it is common to detect large numbers of serodiscordant couples: in concentrated epidemics, 0 to 6% of all couples may be serodiscordant, while in generalized epidemics this figure ranges from 9 to 17% [5]. HIV transmission within serodiscordant couples can contribute substantially to the overall burden of disease. In high prevalence areas like sub-Saharan Africa, approximately half of HIV-positive persons have negative partners, and in low prevalence settings, this proportion may be as high as 75% [5]. A 2013 modeling study among 20 countries in sub-Saharan Africa estimated that 29% (range 10-52%) of new infections occurred within stable serodiscordant couples [6]. An earlier estimate for Zambia alone attributed 60.3 to 94.2% of all new heterosexual HIV infections to serodiscordant married or cohabitating couples [7]. Among MSM, an estimated 33 to 67% of new HIV infections occur within a primary partnership [8, 9].

In this review we summarize biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014 (up to July 1). We begin with the recent World Health Organization (WHO) guidelines for serodiscordant couples, review the evidence for couples counseling, couples-based interventions, and use of antiviral agents as a prevention strategy and briefly address well-accepted forms of prevention including screening and treatment for other sexually transmitted infections (STI) and male circumcision.

II. International guidelines for serodiscordant couples

Serodiscordant couples have attracted a substantial amount of attention for HIV prevention activities - so much so that they have been defined as a “special population” whose care is outlined in multiple sets of normative guidelines beginning with the August 2011 PEPFAR guidelines [10] and the April 2012 WHO guidelines for serodiscordant couples (Figure 1) [11, 12]. These guidelines include a strong recommendation for Couples HIV Testing and Counseling (CHTC) with support for mutual status disclosure, initiation of antiretroviral therapy (ART) irrespective of CD4 cell count or clinical disease stage for people in serodiscordant partnerships, and consideration under some circumstances for the use of pre-exposure prophylaxis (PrEP) for HIV-uninfected persons in serodiscordant partnerships [12]. By year-end 2012, 19 out of 70 countries (27%) had national ART treatment guidelines that matched the WHO’s treatment guidelines for serodiscordant couples [13]. An updated 2014 review of 124 low and middle income countries found that only 26% countries had comparable guidelines in place [14].

Figure 1
WHO Guidelines for couples


I. Biobehavioral approaches

Couples HIV Testing and Counseling: It works

Worldwide, 30 to 70% of HIV-positive persons remain unaware of their status [15]. Over 20 years of history shows evidence that Couples HIV Testing and Counseling (CHTC) increases testing, increases condom use and decreases seroconversion [16, 17]. In the Partners in Prevention HSV/HIV Transmission randomized controlled trial (RCT) (South Africa, 2004 – 2008) knowledge of one’s HIV status and of serodiscordance within the relationship both led to sustained reductions in condomless sex [18]. Furthermore, within the two largest trials of ART treatment as prevention - the Partners Preexposure Prophylaxis (PrEP) Study and the HPTN 052 study - anticipated transmission among couples was greatly reduced with regular testing and intense couples counseling. These studies brought linked HIV transmission events in the study control arms to under 2 events per 100 person years, representing a new standard for prevention in the absence of biomedical intervention [19, 20].

In a recent review, Medley and colleagues catalogue the benefits of CHTC to serodiscordant couples including: decreased transmission within all sexual partners, safer conception, increased psychosocial support, decreased unplanned pregnancy, and increased uptake of and adherence to family planning services, ART, and prevention of mother to child transmission services (PMTCT) [21]. In addition to HIV testing, services that can be provided or referred via CHTC include earlier initiation of ART, reproductive health services, risk reduction counseling and condom distribution, STI screening and treatment, repeat HIV-testing for HIV-negative partners, and voluntary medical male circumcision for HIV-negative male partners [21]. Reproductive health services for serodiscordant couples who wish to conceive may include pre-conception counseling, PMTCT and services such as sperm washing with intrauterine insemination or In Vitro Fertilization [22].

Despite proven benefits, demand for CHTC remains low. One study from Rakai, Uganda, found that uptake of CHTC did not exceed 29% any year from 2003 to 2009 [23]. Additionally, CHTC has traditionally not been available for MSM couples [24] though recent studies demonstrate that it is acceptable and feasible among diverse MSM populations in the U.S., Africa and China [25-27]. The U.S. CDC is currently developing MSM-specific CHTC training guidelines [24].

Additional advances that are changing the landscape of couples-based testing include the July 2012 U.S. Food and Drug Administration’s (FDA) approval of a rapid HIV self-test, OraQuick®, which may facilitate in-home, self-guided couples testing. eSTAMP is a current CDC funded study to explore MSM’s use of OraQuick® and Sure Check ® (a comparable HIV self-test) ( Risk estimators and assessment tools are also under development to help couples make informed sexual health decisions [28] and help care providers identify high-risk serodiscordant couples to guide decisions around use of ART and PrEP [29].

Couples-based interventions

Beyond CHTC, interventions designed specifically for couples may be more effective than individual-focused interventions alone at reducing transmission risk among serodiscordant couples [30]. These interventions promote established risk reduction behaviors (e.g. condom use, decreasing number of partners) as well as couple-relevant strategies including communication and negotiation skills. Although commonly delivered at the dyadic level, group-level couples-focused interventions are also effective. For example, the Zambia NOW2 project compared a couples-focused intervention delivered in pairs or in gender-matched groups (e.g. all females with female counselor). Both study conditions found increased willingness, acceptability, and use of male and female condoms, decreased intimate partner violence and increased positive communication [31]. Couples-based initiatives focused on peer support are also being explored, such as the serodiscordant Couples’ Clubs that are being promoted in Uganda [32].

Couples-based biobehavioral interventions remain an underdeveloped resource. As of April 2014, within the U.S. CDC’s HIV/AIDS Prevention Research Synthesis Project for Evidence Based Interventions (EBIs), out of 84 risk reduction EBIs, none focused on MSM couples and only two addressed heterosexual couples [33]: Connect 2 provided couples counseling for low-income drug users in New York City and significantly reduced unprotected vaginal sex acts over a 12 month period with both the study partner and outside partners [34]. Adaptations of Connect have shown preliminary efficacy in groups as diverse as young, heterosexual couples in South Africa [35] and methamphetamine-involved Black MSM couples in the U.S. [36]. The second EBI, Eban, delivered an intervention tailored for African American heterosexual serodiscordant couples in four U.S. cities and found increased consistent condom use and decreased number of unprotected sex acts [37]. Eban is currently being scaled-up through a community-based implementation trial [38].

A recent systematic review identified 27 biobehavioral interventions for serodiscordant couples [1]. Thirteen studies focused on psycho-educational skills building but the majority had insufficient power to demonstrate change in a biological outcome. The primary elements of skills-building interventions included HIV/STI knowledge, condom use, couple-focused communication, negotiation, problem-solving, goal setting, addressing relationship power imbalances and decision making, strategies for maintaining healthy relationships, and specific focus on negotiating unsafe injection practices among people who inject drugs. An additional 13 studies focused on CHTC for heterosexual couples and one study focused on medication adherence for heterosexual and MSM couples [1].

The limited number of interventions for MSM couples [1, 24] and high prevalence of undiagnosed serodiscordant MSM couples [39] argues for increasing MSM couples-based interventions. A pilot test adapting Connect for use with methamphetamine-involved Black MSM couples shows promise but needs large-scale testing [36]. New interventions should be generated in close collaboration with the specific target communities to work within social and sexual norms. For example, one study found that serodiscordant MSM couples who adopt a “we” (versus “me”) orientation have less unprotected insertive and receptive anal intercourse [40]. Other qualities of MSM couples such as relationship commitment, relationship intimacy and sexual satisfaction are associated with risk taking behavior [41] and may be relevant constructs for MSM-tailored couples interventions. A range of seroadaptive strategies for HIV prevention have also evolved within the MSM and transgender community including serosorting, seropositioning, and negotiated safety [24]. A WHO evidence based review of serosorting for MSM and transgender persons recommends the practice only “under specific circumstances as a harm reduction strategy” but emphasizes the limits of current evidence and specifies that condom use is recommended over serosorting [42].

II. Biomedical approaches

Medical male circumcision

Male circumcision is one of the most effective biomedical interventions for preventing HIV acquisition in heterosexual men as established through three RCTs and a number of observational studies [43]. The reduction in HIV acquisition among heterosexual circumcised men is approximately 60% [44]. Within heterosexual serodiscordant couples where the male is HIV-negative, medical male circumcision is recommended [42]. However, circumcision is not currently recommended for HIV-positive men within serodiscordant relationships or MSM [42]. Two earlier meta-analyses found moderate protective benefit of circumcision among MSM who primarily practice insertive anal intercourse [45, 46] but recent individual studies [47, 48] and an updated WHO evidence review have not confirmed that the benefits of circumcision outweigh potential risks for MSM [42].

Testing and treatment for sexually transmitted infections

Sexually transmitted infections (STI) are common among people living with HIV [49] and amplify transmission [50]. Both partners within serodiscordant couples should be regularly tested as STI may increase both transmission and acquisition vulnerability for HIV [51, 52]. Regular screening and follow-up treatment should be provided to both the HIV-negative and HIV-positive partner to maximize prevention benefit.

Antiretroviral Treatment as Prevention (TasP) (Table 1)

Table 1
Serodiscordant HIV Treatment as Prevention (TasP) studies (Table adapted and expanded from Cohen AIDS 2013)

A key element in the serodiscordant couples’ prevention strategy is the use of antiviral agents as either pre-exposure prophylaxis (PrEP) or in the form of treatment as prevention (TasP) [53]. Blood, viral load [54] and genital tract viral load [55] of the HIV-positive index case predict transmission probability. In 11 out of 13 observational studies [53, 56, 57] and one large RCT [19], antiretroviral treatment reduced HIV transmission within serodiscordant couples, presumably by suppressing viral replication (Table 1). The HPTN 052 study provided an absolute number to the prevention benefits of early ART among serodiscordant heterosexual couples – a reduction in transmission of 96% [19]. A meta-analysis of heterosexual serodiscordant couple studies where the HIV-positive partner is on ART and virally suppressed found 0 transmissions per 100 person years [58], while another similar review of partners on combination ART for at least 6 months found a per act transmission risk estimated at between 1 and 13 per 100,000 sex acts whether or not full viral suppression was achieved [59].

A meta-analysis of 50 publications related to discordant couples studies found a 91% (79 – 96%) reduction in per-partner HIV-1 incidence among couples using ART [60]. In perhaps the largest sample to date, a retrospective cohort analysis of 38,862 serodiscordant heterosexual couples in the People’s Republic of China found a 26% relative reduction in transmission among those on ART [61]. Numerous confounders and the observational nature of this study suggest that it may be a conservative estimate of the actual transmission prevention benefit of ART [62].

There are concerns that controlled trial environments overestimate the “real-world” effectiveness of TasP. We have previously reviewed this topic in detail [63]. Tanser et al. reported that for every 1% increase in ART availability, a 2% decrease in HIV incidence was observed in community settings in KwaZulu-Natal, South Africa [64]. In British Columbia, widespread availability of ART for people who inject drugs appears to have reduced HIV incidence as well [65]. It should be noted that four community-based clinical trials of TasP are underway [66].

There are further challenges to consider. First, unlinked transmissions from outside of the partnership (non-monogamy) are possible. Up to 27% of transmission events in the HPTN052 and Partners Study were attributable to external events [19, 67]. In a recent modeling study of extra-couple HIV transmission in sub-Saharan Africa, researchers estimated that 27 to 61% of all HIV infections among men and 21 to 51% of infections among women were attributable to extra-couple events [68]. Second, couples may not want to start ART early. For example, in a study of 1958 HIV-infected partners in Kenya and Uganda, 50.1% of those eligible for ART had not started therapy within six months of determined eligibility. Even at 24 months, 12.4% of those eligible still had not started therapy [69]. Third, successful TasP approaches require consistent high medication adherence – a constant challenge in practice. Fourth, there are concerns about behavioral risk compensation negating the prevention benefits of earlier ART initiation. A recent study among 957 participants in Cote d’Ivoire does not support this concern as no significant difference was found in sexual behavior risk among early versus standard initiators [70]. In addition, in the face of suppression of viral replication, risk behaviors are unlikely to result in HIV transmission [57].

TasP for MSM couples

The body of evidence and at least one new observational study suggest that TasP confers a similar prevention benefit to MSM serodiscordant couples [57, 71]. The Partner Study is assessing the occurrence of linked transmission among serodiscordant heterosexual and MSM couples who have condomless sex, are not taking PrEP, and have a most recent viral load under 200 c/mL. Thus far, among 308 couple years of follow-up among MSM couples, no linked transmissions were observed [57]. The Opposites Attract Study (running 2012 to 2015), is an observational cohort study enrolling MSM dyads in Australia, Brazil and Thailand ( This study was designed to allow estimates for HIV transmission among partners on and not on ART, virally suppressed versus not virally suppressed, and practicing various levels of condomless anal intercourse.

Antiretroviral Pre-Exposure Prophylaxis (PrEP) (Table 2)

Table 2
PrEP studies (Table adapted and expanded from Cohen AIDS 2013)

Pre-Exposure Prophylaxis (PrEP) refers to the provision of antiretrovirals to an uninfected person prior to exposure to HIV to prevent seroconversion following possible exposure. Thus far PrEP has been tested or is under development in the form of oral pills, vaginal/rectal microbicides, and long-acting vaginal rings and intramuscular injectables [72, 73]. PrEP has been demonstrated to be effective at reducing HIV acquisition among both men and women in four RCTs [20, 74-76] (Table 2).

Oral PrEP

Using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), the Pre-Exposure Prophylaxis Initiative (iPrEx) RCT among 2499 MSM found a 44% reduction in HIV incidence [75] while the TDF2 study among 1200 heterosexual men and women found a 63% reduction [76] and the Partners PrEP study among 4747 heterosexual serodiscordant couples found a 75% reduction [20]. In contrast, prevention benefit of oral TDF/FTC was not found in the Fem-PrEP [77] or the Vaginal and Oral Interventions to Control the Epidemic (VOICE) RCTs [78]. The most probable explanations for these divergent trial results have focused on suboptimal adherence. The U.S. FDA approved TDF/FTC (Truvada®) for use as PrEP in July 2012 and the U.S. CDC released new clinical practice guidelines for PrEP in May 2014 [79]. In brief, these guidelines focus on the recommended use of PrEP for sexually active MSM, heterosexual men and women, and injection drug users who are at “substantial risk of HIV acquisition” and the consideration of PrEP as “one of several options for serodiscordant heterosexual couples during conception and pregnancy”. NEXT-PrEP (HPTN-069) is assessing the safety of maraviroc for HIV-negative people compared to TDF/FTC among MSM, heterosexual men and women and transgender men in 13 U.S. cities (

Vaginal gel

The CAPRISA 004 study tested tenofovir 1% vaginal gel (TFV) used peri-coitally among 889 heterosexual women at high risk of HIV infection and found a 39% reduction in infections overall and a 54% reduction among women who used at least 80% of prescribed doses [74]. Conversely, the VOICE trial (MTN-003) which tested daily TFV use among 5029 heterosexual women in HIV high prevalence areas was discontinued for futility [78]. The Follow-on African Consortium for Tenofovir Studies (FACTS) 001 trial is enrolling women age 18 to 30 across nine sites in South Africa for another trial of TVF. FACTS 001 (2015 anticipated trial completion) will assess the protective benefit of TFV applied pre and post-intercourse for HIV and HSV-2 prevention and FACTS 002 is in the planning phase for a similar trial among adolescent women age 16 – 17 (

In development and testing

Numerous ongoing developments in PrEP science include testing new dosing regimens and new drugs for PrEP including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors (Table 2). Additionally, new drug formulations and delivery methods are under development, including gels, films, long-acting vaginal rings and injectables [72, 80]. Trials in Malawi are underway of the Dapivirine intravaginal ring (RING and ASPIRE – MTN020) [81]. Phase 1 trials are being conducted of long-acting injectables [82]. Five Phase I rectal microbicide trials have been completed in the U.S. and a Phase II trial (MTN017) will be conducted in the U.S., Peru, Thailand and South Africa to compare oral PrEP to TFV gel [83]. There are multipurpose prevention technologies under development that could provide combination protection against pregnancy, HIV, and HSV-2 [84]. Finally, intermittent versus regular use of PrEP is also being studied [85]. Both dosing strategies have been shown to be safe, acceptable and able to achieve adherence in heterosexual couples [86] and MSM [87]. Prevention efficacy of intermittent PrEP is under investigation in at least two ongoing trials in the U.K. (PROUD) ( and France (IPERGAY) (

PrEP for conception (PrEP-C)

Vernazza et al. described a strategy combining TasP and PrEP for safe conception among serodiscordant couples [88] (PrEP-C). A more recent study tested the use of PrEP with serodiscordant couples wishing to conceive naturally: Among 23 couples, TDF/FTC taken before and after timed ovulatory intercourse was safe and effective for preventing transmission during conception for serodiscordant couples where the male was HIV-positive and female was HIV-negative [89]. No transmission events were observed but further large-scale research is needed to validate the results.

Considerable barriers remain for the application of PrEP through primary care clinics. Knowledge and use of PrEP among providers is limited and education interventions are needed. Among doctors in American Academy of HIV Medicine surveyed in Sept 2011, although most were familiar with the results of PrEP studies (90%) and CDC guidelines (78%), only 19% had prescribed PrEP [90]. In a survey of 1175 infectious disease physicians in the U.S. and Canada, while the majority supported the use of PrEP, only 9% had prescribed it [91]. Physicians were most concerned about the real-world effectiveness of PrEP, adherence, risk compensation, toxicity, cost/reimbursement, moral issues, and drug resistance [91]. Much of data needed to address these concerns is (or will soon be) available. For example a sub-analysis of Partners PrEP data found no significant increase in STI, pregnancy or sexual risk taking behavior assessed before and after July 2011 when there was unmasking and knowledge of efficacy of PrEP for HIV prevention [92].

In general, people move in and out of lifestyles that put them at risk for HIV. Thus the 2014 CDC PrEP guidelines for those “at substantial risk of HIV acquisition” are only a starting point for decisions in every-day clinical practice (not to mention the daily decisions that individual patients will make regarding their own self-assessment and interpretation of “substantial risk”). There are logical temporal situations that warrant short-term PrEP use, such as PrEP-C or for a new partnership until concordant HIV-negative status is confirmed, or until an HIV-positive partner is virally suppressed on ART.

Use of monoclonal antibodies

Broadly neutralizing antibodies that form late in HIV infection also have potential to be used for HIV prevention. Several monoclonal broadly neutralizing antibodies have been described [93]. Moncolonal antibodies including VRC01 and PGT121 are entering safety trials with the idea that these antibodies might be used for PrEP or PEP (see below). In addition, Baltimore et al. have generated an adeno-associated virus (AAV) vector that can constitutively generate the PG9 monoclonal antibody [94]. This reagent can protect humanized mice from HIV infection. A similar construct has entered safety trials in Europe [95].

Non-occupational Post-Exposure Prophylaxis (nPEP)

Post-exposure Prophylaxis (PEP) refers to ARVs used soon after a high-risk exposure to HIV to avert infection. The U.S. Public Health Service issued guidelines for PEP in 1996 which were updated in 2005 [96]. Although typically used for occupational exposures, PEP may be recommended following high-risk non-occupational exposures (nPEP) such as unprotected sex with a known or likely HIV positive partner, sexual assault, or injection drug use with a shared or used needle. nPEP is not recommended for those with recurrent HIV exposures, and thus is generally not used for preventing transmission among serodiscordant couples except in emergency cases (e.g. condom failure, rape). However, advances in PrEP technology may also offer new options for nPEP. For example, macaque studies found that a 1% Raltegravir gel applied vaginally three hours after exposure to SHIV prevented transmission in five out of six macaques and showed no evidence of developed drug resistance with repeated use [97].


Marked advances have been made in the past few years in HIV prevention for serodiscordant couples. However, a number of barriers and challenges remain. First, there is great need to scale-up CHTC and advance serodiscordant couples-based interventions, especially for MSM. Second, research is needed to understand how individuals and couples are adopting and adapting to the growing range of biomedical prevention tools (e.g. PrEP, TasP) and how best to promote and maintain use of these tools. Third, many remain unaware of the prevention benefits of ART and ART use faces continued barriers of concern about stigma and side-effects [98].

Adherence is a cross-cutting theme for the success of biomedical prevention efforts among serodiscordant couples and represents one of many examples of how biomedical and behavioral interventions must work in combination. Despite decades of knowledge about adherence barriers, facilitators and interventions [99, 100], optimal, sustained adherence remains elusive. There are only 10 CDC EBIs for HIV medication adherence, none of which are rated as “best-evidence” grading [33].

Combination approaches to HIV prevention show added benefit over individual strategies [101, 102] and are recommended by the WHO [103]. Combination prevention for serodiscordant couples can be implemented at the population level - for example through policies and guidelines to support earlier initiation of ART - as well as at the individual level, such as combining TasP with medical male circumcision and CHTC. In fact, HPTN 052 and the Partners PrEP studies were essentially combination prevention strategies: intensive couples counseling was provided along with a host of other benefits and incentives [104, 105].

Ultimately, all behaviorally acquired HIV transmission depends on risk behaviors within a serodiscordant couple. Focus on the prevention of HIV within these couples remains a critical consideration. Well-demonstrated reductions in risk of transmission reflect the results of intense investigation and critical RCTs. Complete reduction of transmission among serodiscordant couples is theoretically possible. Accordingly, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention.


Compliance with Ethics Guidelines

Conflict of Interest Kathryn E. Muessig declares that she has no conflict of interest.

Myron S. Cohen is an advisory board member for Roche Molecular Systems, BMGF HIV EAP, and Janssen Global Services.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.


1. Jiwatram-Negron T, El-Bassel N. Systematic Review of Couple-Based HIV Intervention and Prevention Studies: Advantages, Gaps, and Future Directions. AIDS Behav. 2014 Jul 2; 2014, epub ahead of print. [PMC free article] [PubMed] ** This systematic review identified 27 biobehavioral interventions for serodiscordant couples. Thirteen studies focused on psycho-educational skills building, 13 studies focused on CHTC for heterosexual couples and one study focused on medication adherence for heterosexual and MSM couples.
2. Burgener A, Sainsbury J, Plummer FA, Ball TB. Systems biology-based approaches to understand HIV-exposed uninfected women. Curr HIV/AIDS Rep. 2010;7:53–59. [PubMed]
3. Persson A. Notes on the concepts of ‘serodiscordance’ and ‘risk’ in couples with mixed HIV status. Glob Public Health. 2013;8:209–220. [PubMed]
4. Bunnell RE, Nassozi J, Marum E, Mubangizi J, Malamba S, Dillon B, et al. Living with discordance: knowledge, challenges, and prevention strategies of HIV-discordant couples in Uganda. AIDS Care. 2005;17:999–1012. [PubMed]
5. Chemaitelly H, Cremin I, Shelton J, Hallett TB, Abu-Raddad LJ. Distinct HIV discordancy patterns by epidemic size in stable sexual partnerships in sub-Saharan Africa. Sex Transm Infect. 2012;88:51–57. [PubMed] * Estimates HIV infection in stable partnerships in 20 countries in sub-Saharan Africa. Percent of serodiscordant partnerships: in concentrated epidemics, 0 to 6%; in generalized epidemics, 9 to 17%. Proportion of HIV-positive persons with negative partners: in high HIV prevalence areas, about half, in low prevalence settings, as high as 75%.
6. Chemaitelly H, Shelton JD, Hallett TB, Abu-Raddad LJ. Only a fraction of new HIV infections occur within identifiable stable discordant couples in sub-Saharan Africa. Aids. 2013;27:251–260. [PubMed]
7. Dunkle KL, Stephenson R, Karita E, Chomba E, Kayitenkore K, Vwalika C, et al. New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet. 2008;371:2183–2191. [PubMed]
8. Goodreau SM, Carnegie NB, Vittinghoff E, Lama JR, Sanchez J, Grinsztejn B, et al. What drives the US and Peruvian HIV epidemics in men who have sex with men (MSM)? PLoS One. 2012;7:e50522. [PMC free article] [PubMed]
9. Sullivan PS, Salazar L, Buchbinder S, Sanchez TH. Estimating the proportion of HIV transmissions from main sex partners among men who have sex with men in five US cities. Aids. 2009;23:1153–1162. [PubMed]
10. PEPFAR Scientific Advisory Board. the HPTN 052 Subcommittee. the HPTN 052 Writing Group PEPFAR Scientific Advisory Board Recommendations for the Office of the US Global AIDS Coordinator: Implications of HPTN 052 for PEPFAR’s Treatment Programs. 2011 Available at
11. World Health Organization . Guidance on couples HIV testing and counselling, including antiretroviral therapy for treatment and prevention in serodiscordant couples: Recommendations for a public health approach. Geneva, Switzerland: 2012. Available at: [PubMed]
12. World Health Organization . Guidance on pre-exposure oral 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. Geneva, Switzerland: 2012. Available at: [PubMed]
13. Gupta S, Granich R, Suthar AB, Smyth C, Baggaley R, Sculier D, et al. Global policy review of antiretroviral therapy eligibility criteria for treatment and prevention of HIV and tuberculosis in adults, pregnant women, and serodiscordant couples. J Acquir Immune Defic Syndr. 2013;62:e87–97. [PubMed]
14. Nelson LJ, Beusenberg M, Habiyambere V, Shaffer N, Vitoria MA, Montero RG, et al. Adoption of national recommendations related to use of antiretroviral therapy before and shortly following the launch of the 2013 WHO consolidated guidelines. Aids. 2014;28(Suppl 2):S217–224. [PubMed] * Review of national policies for the use of antiretroviral therapy among serodiscordant couples compared to 2013 WHO guidelines among low and middle income countries found that only 26% of countries with available data (32/124 countries) had comparable guidelines in place for serodiscordant couples (recommendation of ART initiation regardless of CD4 count).
15. World Health Organization (WHO) United Nations Children’s Fund (UNICEF) Joint United Nations Programme on HIV/AIDS (UNAIDS) Progress report 2011: Global HIV/AIDS response. Epidemic update and health sector progress towards universal access. Geneva, Switzerland: 2011. Available at:
16. Allen S, Tice J, Van de Perre P, Serufilira A, Hudes E, Nsengumuremyi F, et al. Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa. Bmj. 1992;304:1605–1609. [PMC free article] [PubMed]
17. Allen S, Meinzen-Derr J, Kautzman M, Zulu I, Trask S, Fideli U, et al. Sexual behavior of HIV discordant couples after HIV counseling and testing. Aids. 2003;17:733–740. [PubMed]
18. Rosenberg NE, Pettifor AE, De Bruyn G, Westreich D, Delany-Moretlwe S, Behets F, et al. HIV testing and counseling leads to immediate consistent condom use among South African stable HIV-discordant couples. J Acquir Immune Defic Syndr. 2013;62:226–233. [PMC free article] [PubMed]
19. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505. [PMC free article] [PubMed]
20. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399–410. [PMC free article] [PubMed]
21. Medley A, Baggaley R, Bachanas P, Cohen M, Shaffer N, Lo YR. Maximizing the impact of HIV prevention efforts: interventions for couples. AIDS Care. 2013;25:1569–1580. [PubMed] * Provides a comprehensive review of couples-based HIV testing and counseling (CHTC) services, including key elements and benefits of CHTC. Primary focus of paper is on sub-Saharan Africa.
22. Savasi V, Mandia L, Laoreti A, Cetin I. Reproductive assistance in HIV serodiscordant couples. Hum Reprod Update. 2013;19:136–150. [PubMed]
23. Matovu JK, Denison J, Wanyenze RK, Ssekasanvu J, Makumbi F, Ovuga E, et al. Trends in HIV counseling and testing uptake among married individuals in Rakai, Uganda. BMC Public Health. 2013;13:618. [PMC free article] [PubMed]
24. Purcell DW, Mizuno Y, Smith DK, Grabbe K, Courtenay-Quick C, Tomlinson H, et al. Incorporating couples-based approaches into HIV prevention for gay and bisexual men: opportunities and challenges. Arch Sex Behav. 2014;43:35–46. [PubMed] ** Provides a comprehensive review of couples-based HIV prevention approaches among MSM including CHTC, interventions, and biomedical prevention efforts. Identifies a number of key needs for prevention among MSM couples including a need for more evidence-based interventions tailored for MSM couples.
25. Stephenson R, Rentsch C, Sullivan P. High levels of acceptability of couples-based HIV testing among MSM in South Africa. AIDS Care. 2012;24:529–535. [PMC free article] [PubMed]
26. Wagenaar BH, Christiansen-Lindquist L, Khosropour C, Salazar LF, Benbow N, Prachand N, et al. Willingness of US men who have sex with men (MSM) to participate in Couples HIV Voluntary Counseling and Testing (CVCT) PLoS One. 2012;7:e42953. [PMC free article] [PubMed]
27. Wei C, Muessig KE, Bien C, Yang L, Meng R, Han L, et al. Strategies for promoting HIV testing uptake: willingness to receive couple-based and collective HIV testing among a cross-sectional online sample of men who have sex with men in China. Sex Transm Infect. 2014 Apr 23; 2014, epub ahead of print. [PMC free article] [PubMed]
28. Bobashev G, Norton J, Wechsberg W, Toussova O. Are you HIV invincible? A probabilistic study of discordant couples in the context of HIV transmission. PLoS One. 2014;9:e94799. [PMC free article] [PubMed]
29. Kahle EM, Hughes JP, Lingappa JR, John-Stewart G, Celum C, Nakku-Joloba E, et al. An empiric risk scoring tool for identifying high-risk heterosexual HIV-1-serodiscordant couples for targeted HIV-1 prevention. J Acquir Immune Defic Syndr. 2013;62:339–347. [PMC free article] [PubMed]
30. Pequegnat W, Bray JH. HIV/STD Prevention Interventions for Couples and Families: A Review and Introduction to the Special Issue. Couple and Family Psychology: Research and Practice. 2012;1:79–93.
31. Jones D, Kashy D, Chitalu N, Kankasa C, Mumbi M, Cook R, et al. Risk Reduction Among HIV-Seroconcordant and -Discordant Couples: The Zambia NOW2 Intervention. AIDS Patient Care STDS. 2014 Jul 2; 2014, epub ahead of print. [PMC free article] [PubMed] * Demonstrates that a group-level, couples-focused intervention was as effective as dyad-level version of the intervention at increasing willingness, acceptability, and use of male and female condoms, decreasing intimate partner violence and increasing positive communication.
32. Ssenyonjo J. Guidelines for establishing and operating couple’s clubs. 2011 Available at:
33. Centers for Disease Control and Prevention Compendium of Evidence-Based HIV Behavioral Intervenions. U.S. Centers for Disease Control and Prevention. 2014 Available at:
34. El-Bassel N, Gilbert L, Wu E, Witte SS, Chang M, Hill J, et al. Couple-based HIV prevention for low-income drug users from New York City: a randomized controlled trial to reduce dual risks. J Acquir Immune Defic Syndr. 2011;58:198–206. [PubMed]
35. Pettifor A, MacPhail C, Nguyen N, Rosenberg M, Parker L, Sibeko J. Feasibility and acceptability of Project Connect: a couples-based HIV-risk reduction intervention among young couples in Johannesburg, South Africa. AIDS Care. 2014;26:476–482. [PMC free article] [PubMed]
36. Wu E, El-Bassel N, McVinney LD, Hess L, Remien RH, Charania M, et al. Feasibility and promise of a couple-based HIV/STI preventive intervention for methamphetamine-using, black men who have sex with men. AIDS Behav. 2011;15:1745–1754. [PubMed]
37. El-Bassel N, Jemmott JB, Landis JR, Pequegnat W, Wingood GM, Wyatt GE, et al. National Institute of Mental Health Multisite Eban HIV/STD Prevention Intervention for African American HIV Serodiscordant Couples: a cluster randomized trial. Arch Intern Med. 2010;170:1594–1601. [PMC free article] [PubMed]
38. Hamilton AB, Mittman BS, Williams JK, Liu HH, Eccles AM, Hutchinson CS, et al. Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol. Implement Sci. 2014;9:79. [PMC free article] [PubMed]
39. Sullivan PS, Wall KM, O’Hara B, Jones J, Barnes J, DiClemente R, et al. The prevalence of undiagnosed HIV serodiscordance among male couples presenting for HIV testing. Arch Sex Behav. 2014;43:173–180. [PMC free article] [PubMed]
40. Gamarel KE, Starks TJ, Dilworth SE, Neilands TB, Taylor JM, Johnson MO. Personal or relational? Examining sexual health in the context of HIV serodiscordant same-sex male couples. AIDS Behav. 2014;18:171–179. [PMC free article] [PubMed]
41. Starks TJ, Gamarel KE, Johnson MO. Relationship characteristics and HIV transmission risk in same-sex male couples in HIV serodiscordant relationships. Arch Sex Behav. 2014;43:139–147. [PMC free article] [PubMed]
42. World Health Organization . Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people: recommendations for a public health approach. Geneva, Switzerland: 2011. p. 36. Available at: [PubMed]
43. Wamai RG, Morris BJ, Bailis SA, Sokal D, Klausner JD, Appleton R, et al. Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa. J Int AIDS Soc. 2011;14:49. [PMC free article] [PubMed]
44. Mills E, Cooper C, Anema A, Guyatt G. Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men. HIV Med. 2008;9:332–335. [PubMed]
45. Millett GA, Flores SA, Marks G, Reed JB, Herbst JH. Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. Jama. 2008;300:1674–1684. [PubMed]
46. Wiysonge CS, Kongnyuy EJ, Shey M, Muula AS, Navti OB, Akl EA, et al. Male circumcision for prevention of homosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2011:Cd007496. [PubMed]
47. Doerner R, McKeown E, Nelson S, Anderson J, Low N, Elford J. Circumcision and HIV infection among men who have sex with men in Britain: the insertive sexual role. Arch Sex Behav. 2013;42:1319–1326. [PubMed]
48. Zhou C, Raymond HF, Ding X, Lu R, Xu J, Wu G, et al. Anal sex role, circumcision status, and HIV infection among men who have sex with men in Chongqing, China. Arch Sex Behav. 2013;42:1275–1283. [PubMed]
49. Kalichman SC, Pellowski J, Turner C. Prevalence of sexually transmitted co-infections in people living with HIV/AIDS: systematic review with implications for using HIV treatments for prevention. Sex Transm Infect. 2011;87:183–190. [PMC free article] [PubMed]
50. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999;75:3–17. [PMC free article] [PubMed]
51. Cohen MS. Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis. Lancet. 1998;351(Suppl 3):5–7. [PubMed]
52. Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. Am J Reprod Immunol. 2011;65:308–316. [PMC free article] [PubMed]
53. Cohen MS, Smith MK, Muessig KE, Hallett TB, Powers KA, Kashuba AD. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here? Lancet. 2013;382:1515–1524. [PubMed] * Provides a detailed review of the evidence for the prevention benefits of antiretroviral as treatment as prevention and pre-exposure prophylaxis. Reviews evidence from observational studies, randomized controlled trials, ecological and modeling studies. Outlines ongoing and planned unpublished research.
54. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–929. [PubMed]
55. Baeten JM, Kahle E, Lingappa JR, Coombs RW, Delany-Moretlwe S, Nakku-Joloba E, et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med. 2011;3:77ra29. [PMC free article] [PubMed]
56. Anglemyer A, Horvath T, Rutherford G. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. JAMA. 2013;310:1619–1620. [PubMed]
57. Roger A, Brunn T, Cambiano V, Vernazza P, Estrada V, Lunzen J, et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: Partner Study [CROI abstract 153LB]. In Special Issue: Abstracts From the 2014 Conference on Retroviruses and Opportunistic Infections. Tropical Medicine.2014. p. 22. ** This ongoing study is assessing the occurrence of linked transmission among serodiscordant heterosexual and MSM couples who have condomless sex, are not taking PrEP, and have a most recent viral load under 200 c/mL. To date, among 308 couple years of follow-up among MSM couples, no linked transmissions were observed. This is the first, large prospective cohort study to find this level of protection among MSM.
58. Loutfy MR, Wu W, Letchumanan M, Bondy L, Antoniou T, Margolese S, et al. Systematic review of HIV transmission between heterosexual serodiscordant couples where the HIV-positive partner is fully suppressed on antiretroviral therapy. PLoS One. 2013;8:e55747. [PubMed] * This meta-analysis of 6 heterosexual serodiscordant couple studies where the HIV-positive partner is on ART and virally suppressed found 0 transmissions per 100 person years whether or not the viral suppression status was confirmed. The importance of this study is to further support the scientific plausibility of the role of antiretrovirals in reducing HIV transmission via reducing burden of viral particles within the HIV-infected person.
59. Supervie V, Viard JP, Costagliola D, Breban R. Heterosexual Risk of HIV Transmission per Sexual Act Under Combined Antiretroviral Therapy: Systematic Review and Bayesian Modeling. Clin Infect Dis. 2014 Apr 12; 2014, epub ahead of print. [PMC free article] [PubMed]
60. Baggaley RF, White RG, Hollingsworth TD, Boily MC. Heterosexual HIV-1 infectiousness and antiretroviral use: systematic review of prospective studies of discordant couples. Epidemiology. 2013;24:110–121. [PubMed] * This meta-analysis of 50 publications related to discordant couples studies found a 91% (79 – 96%) reduction in per-partner HIV-1 incidence among couples using antiretroviral therapy (based on the 9 studies that provided stratified data for comparing participants on and not on ART. The importance of this study is its role in advancing the evidence for the benefit of ART for prevention among serodiscordant couples while also showing that there is NOT a non-zero transmission risk even in the presence of ART.
61. Jia Z, Mao Y, Zhang F, Ruan Y, Ma Y, Li J, et al. Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study. Lancet. 2013;382:1195–1203. [PubMed]
62. Vermund SH. Treatment as prevention for HIV in China. Lancet. 2013;382:1159–1161. [PubMed]
63. Smith MK, Powers KA, Muessig KE, Miller WC, Cohen MS. HIV treatment as prevention: the utility and limitations of ecological observation. PLoS Med. 2012;9:e1001260. [PMC free article] [PubMed]
64. Tanser F, Barnighausen T, Grapsa E, Zaidi J, Newell ML. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science. 2013;339:966–971. [PMC free article] [PubMed]
65. Wood E, Milloy MJ, Montaner JS. HIV treatment as prevention among injection drug users. Curr Opin HIV AIDS. 2012;7:151–156. [PubMed]
66. Boily MC, Masse B, Alsallaq R, Padian NS, Eaton JW, Vesga JF, et al. HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention. PLoS Med. 2012;9:e1001250. [PMC free article] [PubMed]
67. Eshleman SH, Hudelson SE, Redd AD, Wang L, Debes R, Chen YQ, et al. Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial. J Infect Dis. 2011;204:1918–1926. [PMC free article] [PubMed]
68. Bellan SE, Fiorella KJ, Melesse DY, Getz WM, Williams BG, Dushoff J. Extra-couple HIV transmission in sub-Saharan Africa: a mathematical modelling study of survey data. Lancet. 2013;381:1561–1569. [PMC free article] [PubMed]
69. Mujugira A, Celum C, Thomas KK, Farquhar C, Mugo N, Katabira E, et al. Delay of Antiretroviral Therapy Initiation Is Common in East African HIV-Infected Individuals in Serodiscordant Partnerships. J Acquir Immune Defic Syndr. 2014;66:436–442. [PMC free article] [PubMed]
70. Jean K, Gabillard D, Moh R, Danel C, Fassassi R, Desgrees-du-Lou A, et al. Effect of early antiretroviral therapy on sexual behaviors and HIV-1 transmission risk among adults with diverse heterosexual partnership statuses in Cote d’Ivoire. J Infect Dis. 2014;209:431–440. [PMC free article] [PubMed]
71. Muessig KE, Smith MK, Powers KA, Lo YR, Burns DN, Grulich AE, et al. Does ART prevent HIV transmission among MSM? Aids. 2012;26:2267–2273. [PMC free article] [PubMed]
72. McGowan I. An overview of antiretroviral pre-exposure prophylaxis of HIV infection. Am J Reprod Immunol. 2014;71:624–630. [PubMed] * Reviews the current state of the science for pre-exposure prophylaxis (PrEP) including a review of ongoing and upcoming trials of evolving new PrEP approaches: intermittent dosing strategies, microbicides, long-acting intravaginal rings, long-acting intramuscular injections.
73. Plosker GL. Emtricitabine/tenofovir disoproxil fumarate: a review of its use in HIV-1 pre-exposure prophylaxis. Drugs. 2013;73:279–291. [PubMed]
74. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168–1174. [PMC free article] [PubMed]
75. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–2599. [PMC free article] [PubMed]
76. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–434. [PubMed]
77. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–422. [PMC free article] [PubMed]
78. Marrazzo J, Ramjee G, Nair G, Palanee T, Mkhize B, Nakabiito C, et al. Pre-exposure prophylaxis for HIV in women: Daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE study (MTN-003). 20th Conference on Retroviruses and Opportunistic Infections; Atlanta, Georgia. 2013.
79. Centers for Disease Control and Prevention Pre-exposure prophylaxis for the prevention of HIV infection in the United States - 2014: A clinical practic guideline. 2014 Available at:
80. Mayer KH. Antiretroviral chemoprophylaxis: state of evidence and the research agenda. Clin Infect Dis. 2014;59(Suppl 1):S47–51. [PMC free article] [PubMed]
81. Devlin B, Nuttall J, Wilder S, Woodsong C, Rosenberg Z. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013;100(Suppl):S3–8. [PubMed]
82. Spreen WR, Margolis DA, Pottage JC., Jr Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013;8:565–571. [PMC free article] [PubMed]
83. McGowan I. The development of rectal microbicides for HIV prevention. Expert Opin Drug Deliv. 2014;11:69–82. [PubMed]
84. Friend DR, Clark JT, Kiser PF, Clark MR. Multipurpose prevention technologies: products in development. Antiviral Res. 2013;100(Suppl):S39–47. [PubMed]
85. Kibengo FM, Ruzagira E, Katende D, Bwanika AN, Bahemuka U, Haberer JE, et al. Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial. PLoS One. 2013;8:e74314. [PMC free article] [PubMed]
86. Roberts ST, Heffron R, Ngure K, Celum C, Kurth A, Curran K, et al. Preferences for Daily or Intermittent Pre-exposure Prophylaxis Regimens and Ability to Anticipate Sex Among HIV Uninfected Members of Kenyan HIV Serodiscordant Couples. AIDS Behav. 2014 May 30; 2014, Epub ahead of print. [PMC free article] [PubMed]
87. Mutua G, Sanders E, Mugo P, Anzala O, Haberer JE, Bangsberg D, et al. Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers. PLoS One. 2012;7:e33103. [PMC free article] [PubMed]
88. Vernazza PL, Graf I, Sonnenberg-Schwan U, Geit M, Meurer A. Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child. Aids. 2011;25:2005–2008. [PubMed]
89. Whetham J, Taylor S, Charlwood L, Keith T, Howell R, McInnes C, et al. Pre-exposure prophylaxis for conception (PrEP-C) as a risk reduction strategy in HIV-positive men and HIV-negative women in the UK. AIDS Care. 2014;26:332–336. [PubMed]
90. Tellalian D, Maznavi K, Bredeek UF, Hardy WD. Pre-exposure prophylaxis (PrEP) for HIV infection: results of a survey of HIV healthcare providers evaluating their knowledge, attitudes, and prescribing practices. AIDS Patient Care STDS. 2013;27:553–559. [PubMed]
91. Karris MY, Beekmann SE, Mehta SR, Anderson CM, Polgreen PM. Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada. Clin Infect Dis. 2014;58:704–712. [PMC free article] [PubMed]
92. Mugwanya KK, Donnell D, Celum C, Thomas KK, Ndase P, Mugo N, et al. Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis. Lancet Infect Dis. 2013;13:1021–1028. [PMC free article] [PubMed]
93. West AP, Jr., Scharf L, Scheid JF, Klein F, Bjorkman PJ, Nussenzweig MC. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell. 2014;156:633–648. [PMC free article] [PubMed]
94. Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature. 2012;481:81–84. [PMC free article] [PubMed]
95. International AIDS Vaccine Initiative (IAVI) IAVI Portfolio: AAV1-PG9. 2014 Available at:
96. Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005;54:1–17. [PubMed]
97. Dobard C, Sharma S, Parikh UM, West R, Taylor A, Martin A, et al. Postexposure protection of macaques from Vaginal SHIV infection by topical integrase inhibitors. Sci Transl Med. 2014;6:227ra235. [PubMed]
98. Kahn TR, Desmond M, Rao D, Marx GE, Guthrie BL, Bosire R, et al. Delayed initiation of antiretroviral therapy among HIV-discordant couples in Kenya. AIDS Care. 2013;25:265–272. [PMC free article] [PubMed]
99. Koenig LJ, Lyles C, Smith DK. Adherence to antiretroviral medications for HIV pre-exposure prophylaxis: lessons learned from trials and treatment studies. Am J Prev Med. 2013;44:S91–98. [PubMed] * Synthesizes the evidence for the importance of adherence across multiple biomedical HIV prevention trials.
100. Amico KR, Stirratt MJ. Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence. Clin Infect Dis. 2014;59(Suppl 1):S55–60. [PubMed] * Synthesizes current research on the importance of adherence in pre-exposure prophlyaxis (PrEP) studies including within trials and open-label studies. Finds that current evidence base lacks sufficient information about uptake, adherence and persistence with new PrEP technologies.
101. Padian NS, McCoy SI, Manian S, Wilson D, Schwartlander B, Bertozzi SM. Evaluation of large-scale combination HIV prevention programs: essential issues. J Acquir Immune Defic Syndr. 2011;58:e23–28. [PubMed]
102. Lasry A, Sansom SL, Wolitski RJ, Green TA, Borkowf CB, Patel P, et al. HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies. AIDS. 2014;28:1521–1529. [PubMed]
103. World Health Organization . Priority interventions HIV/AIDS prevention, treatment and care in the health sector (2010 version) World Health Organization; Geneva, Switzerland: 2010. Available at:
104. McNairy ML, Cohen M, El-Sadr WM. Antiretroviral therapy for prevention is a combination strategy. Curr HIV/AIDS Rep. 2013;10:152–158. [PubMed]
105. Celum C, Baeten JM, Hughes JP, Barnabas R, Liu A, Van Rooyen H, et al. Integrated strategies for combination HIV prevention: principles and examples for men who have sex with men in the Americas and heterosexual African populations. J Acquir Immune Defic Syndr. 2013;63(Suppl 2):S213–220. [PMC free article] [PubMed]
106. Birungi J, Wang H, Ngolobe M, Muldoon K, Khanakwa S, King R. Lack of effectiveness of antiretroviral therapy (ART) as an HIV prevention tool for serodiscordant couples in rural ART program without viral load monitoring in Uganda. 19th International AIDS Conference; Washington, D.C.. 2012.
107. Bunnell R, Ekwaru JP, Solberg P, Wamai N, Bikaako-Kajura W, Were W, et al. Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda. AIDS. 2006;20:85–92. [PubMed]
108. del Romero J, Castilla J, Hernando V, Rodriguez C, Garcia S. Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study. BMJ. 2010;340:c2205. [PubMed]
109. Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375:2092–2098. [PMC free article] [PubMed]
110. Hernando V, del Romero J, Garcia S, Rodriguez C, del Amo J, Castilla J. Reducing sexual risk behavior among steady heterosexual serodiscordant couples in a testing and counseling program. Sex Transm Dis. 2009;36:621–628. [PubMed]
111. Melo MG, Santos BR, De Cassia Lira R, Varella IS, Turella ML, Rocha TM, et al. Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, southern Brazil. Sex Transm Dis. 2008;35:912–915. [PubMed]
112. Reynolds SJ, Makumbi F, Nakigozi G, Kagaayi J, Gray RH, Wawer M, et al. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. Aids. 2011;25:473–477. [PMC free article] [PubMed]
113. Sullivan P, Kayintekore K, Chomba E, Karita E, Mwananyanda L, Vwalika C. Reduction of HIV transmission risk while prescribed antiretroviral therapy (ARVT): Misclassification of ARVT status as a methodological issue. AIDS Res Hum Retroviruses. 2010;26:A1–A184.
114. Wang L, Ge Z, Luo J, Shan D, Gao X, Ding GW, et al. HIV Transmission Risk Among Serodiscordant Couples: A Retrospective Study of Former Plasma Donors in Henan, China. J Acquir Immune Defic Syndr. 2010;55:232–238. [PMC free article] [PubMed]
115. Lu W, Zeng G, Luo J, Duo S, Xing G, Guo-Wei D, et al. HIV transmission risk among serodiscordant couples: a retrospective study of former plasma donors in Henan, China. J Acquir Immune Defic Syndr. 2010;55:232–238. [PMC free article] [PubMed]
116. Castilla J, Del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 2005;40:96–101. [PubMed]
117. Musicco M, Lazzarin A, Nicolosi A, Gasparini M, Costigliola P, Arici C, et al. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission. Arch Intern Med. 1994;154:1971–1976. [PubMed]
118. Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007;2:e27. [PMC free article] [PubMed]