Timely HIV diagnosis is a necessary step for accessing HIV care and treatment and an important step for reducing HIV transmission.1–3 Despite recent scale-up of HIV counseling and testing in sub-Saharan Africa, many adults still have not been tested for HIV.3 In Malawi in 2009, 11% of the adult population was infected with HIV, but only one third of HIV-infected adults knew that they were HIV infected.4 The remaining two thirds either never tested or received an HIV-negative result at the time of their last test.4 Because persons unaware of HIV infection contribute disproportionately to HIV transmission,4–6 strategies are needed to identify these persons.
Several strategies are available for increasing HIV testing and counseling (HTC). Stand-alone voluntary counseling and testing addresses a need for client-driven HTC but misses those who do not seek services. Opt-out HTC reaches most careseekers in many clinical settings,7 but misses populations that do not routinely present for care. Community-based strategies, such as door-to-door HTC, have been effective and reasonably efficient at reaching first-time testers.8–13 However, such efforts typically have been implemented once in settings where most adults have never been tested. In settings where most adults have been tested, the efficiency of door-to-door testing is diminished, as many prevalent cases have already been detected.14,15 In Malawi, where 11% of adults are HIV-infected, and a large share know their HIV status, it would be necessary to test many adults to identify each new case of HIV.
In light of recent scale-up of HTC, new strategies are needed to identify hard-to-reach undiagnosed cases of HIV infection. Asking high-risk patients with sexually transmitted infections (STIs) and newly diagnosed HIV to recruit social contacts is one possible strategy. Success of such a strategy would hinge on 3 premises: (1) Feasibility: STI patients can successfully recruit members of their social networks, (2) Effectiveness: STI patients have social networks with high HIV prevalence, and (3) Efficiency: Few contacts require screening to identify 1 new case of HIV. Demonstration projects of social contact recruitment in the United States have led to improved case finding, with HIV-infected persons and high-risk HIV-uninfected persons more likely to recruit other HIV-infected persons.16–18 Similarly, respondent-driven sampling has effectively found undiagnosed cases of STIs and HIV in concentrated epidemics19 and been piloted in generalized epidemics.20–22 However, social contact recruitment based on STI and HIV status has never been formally assessed as a strategy to identify undiagnosed cases of HIV in a generalized HIV epidemic. This strategy is promising in light of “differential affiliation,” persons affiliating with social groups who have comparable HIV risk.23
In an STI clinic in Lilongwe, Malawi, we evaluated a social contact recruitment program. We assessed (1) whether newly diagnosed HIV-infected and HIV-uninfected STI patients were able to recruit social network members for HIV screening (feasibility), (2) the prevalence of HIV among contacts who presented (effectiveness), and (3) number of contacts recruited to identify 1 new case of HIV (efficiency). For assessments of feasibility, effectiveness, and efficiency, we compared contacts of HIV-infected and HIV-uninfected STI patients to contacts of community controls.
This study was conducted at the STI clinic at Kamuzu Central Hospital in Lilongwe, Malawi, from November 2010 to February 2012. This clinic serves persons with symptomatic STIs and their partners. During this period, patients were routinely assessed for STIs using Malawi's syndromic management algorithm. Using this algorithm, patients reporting STI symptoms received clinical examinations. In clinical examinations, patients were examined for genital ulcer disease, urethral/vaginal discharge, genital warts, and bubo. Females were screened for lower abdominal pain and males for balanitis. During this period, all patients were offered HTC using parallel HIV-1 antibody rapid tests: Alere Determine HIV-1/2 Rapid Test and Trinity Biotech Uni-Gold HIV Rapid Test. Patients with 2 positive HIV antibody tests were classified as having established HIV infection. Patients with at least 1 HIV-negative antibody test result were offered HIV RNA PCR screening with Abbott Real Time HIV-1 Assay (Abbott Park, Illinois) through CHAVI 001, a concomitant study in this setting. Patients with positive PCR results were classified with acute HIV infection (AHI), and those with negative PCR results were classified as HIV uninfected.
Seed Participant Procedures
Three groups of 45 “seeds” were enrolled: newly diagnosed HIV-infected STI clinic patients with STI syndromes, HIV-uninfected STI clinic patients with STI syndromes, and community controls (Fig. 1).
To recruit clinic seeds, up to 4 patients were randomly selected from the STI clinic roster each day and screened for participation. Patients were eligible for seed participation if they were aged 18–45 years, residing within the Lilongwe City catchment area, diagnosed with an STI syndrome in the last 2 weeks, and not referred by a sexual contact. Patients who previously received an HIV-positive test result were excluded. All patients recently diagnosed with AHI were invited to participate as HIV-infected seeds, regardless of random selection from the clinic roster or meeting other eligibility criteria.
Community control seeds were recruited from the STI clinic catchment area using frequency matching based on clinic seeds' ages, genders, and areas. Forty-five areas (the primary Lilongwe geographic units) were selected from the areas where the 90 clinic seeds resided. Within each of the 45 areas, geographic coordinates were selected randomly in SAS 9.2 to identify the location for community recruitment. A trained community team of educators, counselors, and nurses with GPS devices were given the coordinates and asked to recruit 1 person within a specified age range and gender at each set of coordinates. The community team followed a structured set of procedures to identify which residences and residents to approach. Community members at these residences were eligible if they met the specified age and gender criteria, were willing to test for HIV, and had not tested HIV positive previously. Once an eligible person was identified, the study was described and the person was invited to participate. For those community seeds who agreed to participate, all study procedures were conducted at a private location in the community. Before community recruitment, community workers sensitized community leaders to facilitate participation.
Study procedures were similar for community and clinic seeds. All seeds had 1 initial visit and were encouraged to come to the clinic 1 month later for 1 follow-up visit. A travel reimbursement of approximately $5 was provided for each study visit. At the initial visit, participants were consented by trained study staff and asked to respond to an interviewer-administered questionnaire. The questionnaire assessed demographics, socioeconomic status, HIV testing history, sexual behaviors, and characteristics of 5 social contacts. Clinic seeds had HIV and STI information transferred from clinic records to study forms at their initial visit. Community seeds received HTC in the community at their initial visit and were assessed for STIs using the clinic's syndromic management algorithm at follow-up. At follow-up, all seeds answered questions about their participation in the program and were given $2 for each successfully referred contact.
The social contact recruitment program was described to seeds at the initial visit. It was described as a “health promotion program,” rather than an STI or HIV program to avoid stigma. Study staff explained that the program included HIV testing, STI screening, and other health services, including blood pressure screening and a health discussion. Seeds were asked to recruit up to 5 contacts and provided with 5 vouchers linked to the seed's study identification number. Seeds were encouraged to refer social contacts who they thought would benefit from the health promotion program. Seeds were permitted to define whom they considered a social contact and were not restricted from recruiting sexual partners or family members.
Social Contact Participant Procedures
Contacts were eligible if they were aged 18–45 years of age and residing in the Lilongwe City catchment area. When contacts presented, they were consented; interviewed about their demographic characteristics, sexual behavior, and HIV testing history; assessed for STIs using the same syndromic management procedures; and assessed for HIV using the same antibody test protocol as seeds. Contacts were not systematically assessed for AHI24 and were not excluded if they already knew their HIV status. Contacts were also offered blood pressure screening and a health promotion discussion on cardiovascular disease, diabetes, clean water and hygiene, family planning, STIs, or malaria. They received $5 for transport reimbursement.
Descriptive statistics were calculated for seeds (Table 1) and contacts (Table 3) using means and proportions. Proportions of seeds with each characteristic were compared between groups using χ2 tests.
To assess feasibility, the proportion of seeds who successfully recruited at least 1 contact was compared between groups using a χ2 test. The mean number of contacts recruited per seed was compared using analysis of variance.
To assess effectiveness, the prevalence of previous HIV testing, sexual behaviors, STIs, and HIV were compared between groups. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated using generalized estimating equations with a binomial distribution, log link, and exchangeable correlation matrix to account for clustering by seed. We also explored whether the prevalence of these behaviors and infections was different between the contacts of patients with established and acute HIV infection.
To assess efficiency, we calculated the proportion of contacts newly tested for HIV and compared proportions between groups using generalized estimating equations with a binomial distribution, log link, and an exchangeable correlation matrix. The number of contacts needed to test to identify 1 new case of HIV or any STI syndrome was also calculated using generalized estimating equations with a log link, Poisson distribution, and exchangeable correlation matrix.
Permission for collecting these data was granted by the Malawi National Health Science Research Committee and the School of Medicine Institutional Review Board at the University of North Carolina at Chapel Hill. All seeds and contacts provided written consent to participate. Information about seeds was not shared with contacts and vice versa.
Seed Participant Characteristics
Of 245 randomly selected clinic participants, 118 were eligible. The most common reasons for noneligibility were known HIV-positive status (N = 57, 45%), not meeting age or catchment area requirements (N = 13, 10%), being the sex partner of an STI patient (N = 15, 12%), or not having an STI (N = 12, 9%). Of the 118 eligible clinic participants, 76% consented (N = 90). In the community, 108 locations were visited to recruit 45 community seeds. Some coordinates did not lead to residences (N = 22), some led to residences with nobody home (N = 10), and some led to residences where no one met the eligibility criteria (N = 25). Of the 48 residences with an eligible person present, 93% were willing to participate. As specified by the protocol, the seed population included 45 newly diagnosed HIV-infected patients, 45 HIV-uninfected patients, and 45 community controls. Twelve HIV-infected seeds had AHI.
Among all seeds, 45% were male (Table 1), the mean age was 27.6 years, and most (61%) were married. Most (71%) had not used a condom in any of their last 5 sex acts. In the last 3 months, 12% exchanged sex for money and 16% had 2 or more sex partners, although proportions were higher among clinic-based seeds. Almost all seeds (80%) had been tested for HIV at least once, although this was lowest (60%) among HIV-infected seeds. Among HIV-infected clinic seeds, 27% had recently been diagnosed with AHI. Among community seeds, 1 (2%) had HIV. All clinic seeds had an STI except for 8 of the seeds with AHI.
Overall, the 135 seeds recruited 244 contacts (36% of the maximum number possible). The proportion recruiting at least 1 contact was somewhat higher among community seeds (69%) than among HIV-infected clinic seeds (47%) or HIV-uninfected clinic seeds (53%) (P = 0.09) (Table 2). However, among seeds recruiting at least 1 contact, the mean number of contacts was the same between the 3 groups: HIV-infected seeds: 2.9, HIV-uninfected seeds: 3.4, and community seeds: 3.3 (P = 0.5).
Among HIV-infected seeds, 39% of those with established HIV infection and 67% of those with AHI recruited at least 1 contact. The mean number of contacts recruited per seed was higher among those with AHI (mean = 2.0) than established HIV infection (mean = 1.1). This difference may have been due to additional counseling provided through CHAVI 001.
Social Contact Characteristics
Of the 244 contacts recruited, 228 (93%) participated. Of those who did not, most were ineligible due to being older than 45 years. Of the participating contacts, 62% were friends or neighbors of the seed, 18% were family members (primarily siblings and cousins), 11% were sexual contacts (primarily spouses), and 8% had another relationship. Most had known the recruiting seed for ≥1 year (79%), reported knowing the seed very well (87%), saw the seed several times each week (93%), interacted with the seed primarily at a home (81%), and described conversation as their primary activity together (89%).
Among contacts, 46% were male (Table 3), the mean age was 27.5 years, and most (59%) were married. Most (78%) reported at least on HIV test before the study. Most (76%) had not used a condom during any of the last 5 sex acts. In the last 3 months, 19% exchanged sex for money and 8% had ≥2 sex partners.
Contacts of the HIV-infected clinic seeds were more likely to be HIV-infected (31%) than contacts of community seeds (11%). HIV prevalence was 3.2 times higher (95% CI: 1.3 to 7.8) among contacts of HIV-infected clinic seeds than among contacts of community seeds (Table 4). Contacts of the HIV-uninfected clinic seeds were not more likely to be HIV-infected (10% established HIV infection and 1% AHI) than contacts of community seeds (PR: 1.1, 95% CI: 0.4 to 3.3). When analyses were restricted to nonsexual contacts, these PR estimates were similar: 3.0 and 1.4, respectively. When analyses were adjusted for seed sexual behavior (condom use and number of partners), PR estimates were also similar: 3.4 and 1.0, respectively.
The contacts of the HIV-infected and HIV-uninfected clinic seeds were more likely to have an STI syndrome (29% and 19%, respectively) than the contacts of the community seeds (9%). STI syndrome prevalence was 2.0 times higher (95% CI: 0.8 to 5.3) among contacts of HIV-infected clinic seeds and 3.2 times higher (95% CI: 1.4 to 7.2) among contacts of HIV-uninfected clinic seeds compared with contacts of community seeds. When analyses were restricted to nonsexual contacts PR estimates were similar: 1.9 and 3.3, respectively. When analyses were adjusted for seed sexual behavior, PR estimates were also similar: 2.1 and 3.2, respectively.
Contacts of seeds with established HIV infection and AHI were compared. The prevalence of HIV was nearly the same among contacts of seeds with established HIV infection (32%) and contacts of seeds with AHI (30%). Most contacts were not assessed for AHI. The prevalence of an STI was higher (24%) among the contacts of clinic seeds with established HIV infection than among contacts of clinic seeds with AHI (10%).
Of the 180 HIV-uninfected contacts, few (19%) were tested for HIV for the first time through the study. Of 35 contacts with HIV infection, 7 (20%) were being tested for HIV the first time through the study, 13 (37%) had tested HIV-negative previously and seroconverted afterward, and 15 (43%) already knew that they were HIV infected. Of the 20 contacts who learned their HIV-positive status through the study, 7 were recruited by HIV-infected seeds, 7 by HIV-uninfected seeds, and 6 by community seeds.
To identify 1 new case of HIV, 8.1 contacts of HIV-infected clinic seeds, 9.7 contacts of HIV-uninfected clinic seeds, and 17.5 contacts of community seeds were screened. To identify 1 new case of an STI, 5.5 contacts of HIV-infected clinic seeds, 3.5 contacts of HIV-uninfected clinic seeds, and 11.4 contacts of community seeds were screened. To identify 1 new case of an STI or HIV, 3.7 contacts of HIV-infected clinic seeds, 2.8 contacts of HIV-uninfected clinic seeds, and 7.3 contacts of community seeds were screened.
Asking STI patients to recruit their social contacts was a feasible, effective, and efficient way of diagnosing new HIV cases in a generalized HIV epidemic. Half of the clinic seeds in our study were able to successfully recruit at least 1 contact, and contacts of HIV-infected clinic seeds had a higher HIV prevalence than contacts of community seeds. To identify 1 new case of HIV infection, only 8–10 contacts of clinic seeds needed to be tested for HIV, much better efficiency than random testing in the population.
High-risk persons tend to associate with other persons who engage in similar high-risk activities. However, this relationship typically has been assessed in concentrated HIV epidemics,20,24,25 with fewer assessments in generalized epidemics.21 In contrast, we used social contact recruitment in a generalized epidemic among persons with biological evidence of risk—a newly diagnosed case of HIV and/or an STI. By using a well-designed community-based comparison group, we were able to demonstrate effectiveness. Even in the context of a generalized HIV epidemic, STI and HIV risk was not evenly distributed, but rather clustered in social networks.
Understanding the reasons for social contact recruitment effectiveness is important. One possible explanation is that members of the same social networks have similar risk behaviors. Formal exploration of this possibility is being assessed in a separate analysis. However, informal comparisons of sexual behavior between seeds and corresponding contacts suggest this explanation alone does not account for these results. An alternative explanation for the observed HIV disease clustering is that the social network itself is a risk factor. Contacts of HIV-infected seeds may be part of sexual networks with a higher HIV prevalence. In other words, the network population may be a more salient exposure than the behaviors within that network, an observation that has been made in concentrated epidemics25,26 and other generalized27,28 HIV epidemic settings. Sexual relationships between seeds and contacts are not the primary reason for the observed clustering, although a high prevalence of HIV concordance has been observed among couples in this setting.29 When analyses were restricted to only nonsexual contacts, elevated HIV prevalence persisted.
Social contact recruitment by patients with AHI may also be a promising way of effectively finding the “leading edge” of the HIV epidemic. In this study, we were only able to explore this possibility through enrollment of a few persons with AHI. On average, these patients were willing to recruit 2 social contacts and the HIV prevalence among their contacts was high (30%). However, we were not able to explore whether their contacts had AHI. Exploring AHI in social contacts of AHI patients is a key next step, as these persons may be exposed to networks with elevated HIV incidence.
Social contact recruitment was feasible in all groups but more feasible for community-based seeds. Clinic-based seeds recruited fewer social contacts. Lower recruitment may have been due to stigma or fear of contacts learning their STI or HIV results, factors under exploration in an analysis of acceptability. Despite clinic-based seeds recruiting fewer contacts, half of the seeds were successfully able to recruit at least 1 contact.
Lower feasibility coupled with greater effectiveness led to greater efficiency of social contact recruitment by clinic-based seeds. The total number of newly diagnosed contacts was approximately the same in all 3 groups. However, the number of contacts needed to test to identify 1 new case of HIV was considerably lower among contacts of clinic-based seeds. For routine implementation, screening fewer high-risk contacts is more efficient than more low-risk contacts. Efficiency may be improved further by targeting those seeds most likely to recruit undiagnosed HIV-infected persons. Such targeting could reduce the number of additional persons presenting to a busy clinical setting while simultaneously reaching those with greatest need. Demographic, behavioral, and relationship characteristics associated with recruitment of high-risk contacts is a direction to explore.
Several operational considerations deserve further research. First, in addition to receiving $5 per research visit, all seeds received a $2 incentive for each contact who presented to the clinic. This amount was considered motivational but not coercive by local staff and community advisors. However, because this amount did not vary, we could not assess whether a larger incentive would have improved contact recruitment. Additionally, all seeds were exposed to the same messages regarding contact recruitment. They were encouraged to bring friends who would benefit from the health promotion program. But other messages, such as encouraging recruitment of high-risk contacts, may be more effective. Future studies could randomize whether different incentive amounts and messages are associated with different degrees of feasibility, effectiveness, and efficiency.
Replication in other clinical settings is warranted. STI clinics serve patients with greater biological and behavioral risk for HIV, and these patients were part of social networks with elevated undiagnosed HIV infection. Whether newly diagnosed HIV-infected patients in other settings would also be part of higher risk networks is unknown. However, recruitment by only HIV-infected seeds may result in inadvertent disclosure of seed HIV status. Assessment in other settings, with attention to inadvertent disclosure, is an important direction for future research.
Our findings reflect a novel strategy for addressing a pressing public health need: identifying undiagnosed hard-to-reach cases of HIV infection. We demonstrated that asking STI patients to recruit their social contacts was a feasible, effective, and efficient way of identifying this population. These observations support social contact recruitment extending the reach of the health care screening system. Such an approach could become a powerful way of identifying HIV in hard-to-reach populations earlier.
The authors would like to thank the clinic and community staff and participants for their contributions.
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