Amanda Tichacek

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.

Access to adequate nutrition is a major potential obstacle to antiretroviral adherence among HIV-infected individuals in Rwanda.

Despite the massive expansion of antiretroviral drugs in Africa, little is known about the resulting changes in sexual behavior or obstacles to antiretroviral therapy (ART) adherence. Our evaluation of Rwandan adults on ART found no increase in risky sexual behaviors, but an obstacle to ART initiation and adherence for 76% of patients was a fear of developing too much appetite without enough to eat. Access to adequate nutrition may be a major determinant for long-term adherence to ART.

Enrollment and retention of HIV discordant couples in Lusaka, Zambia.

Background:Biased enrollment and attrition compromise the power of clinical trials and limit generalizability of findings. We identify predictors of enrollment and retention for HIV-discordant couples enrolled in prospective studies in Zambia. Principal Findings:A total of 1995 discordant couples were invited to enroll. Predictors of nonenrollment, loss to follow-up, and missed appointments were evaluated using multivariate models. M+F− couples were more likely to be eligible and to enroll and less likely to be lost to follow-up than F+M− couples. Substantial losses to follow-up occurred between testing and enrollment (21.3% of M+F− and 28.1% of F+M−) and between enrollment and the first follow-up visit (24.9% of M+F− and 30.5% of F+M−). Among M+F− and F+M− couples, residence far from the clinic, younger age, and womens age at first intercourse ≤17 years were predictive of attrition. No income, ≤2 lifetime sex partners, no history of sexually transmitted infection in women, and recent extramarital contact in their male partners predicted attrition in F+M− couples. Conclusions:Discordant couples are critical to observational studies and clinical trials to prevent male-to-female and female-to-male transmission. Retention biases must be taken into account during analysis. Run-in designs that delay randomization may improve retention in clinical trials.

Promotion of couples' voluntary HIV counselling and testing in Lusaka, Zambia by influence network leaders and agents

Objectives Hypothesising that couples’ voluntary counselling and testing (CVCT) promotions can increase CVCT uptake, this study identified predictors of successful CVCT promotion in Lusaka, Zambia. Design Cohort study. Setting Lusaka, Zambia. Participants 68 influential network leaders (INLs) identified 320 agents (INAs) who delivered 29 119 CVCT invitations to heterosexual couples. Intervention The CVCT promotional model used INLs who identified INAs, who in turn conducted community-based promotion and distribution of CVCT invitations in two neighbourhoods over 18 months, with a mobile unit in one neighbourhood crossing over to the other mid-way through. Primary outcome The primary outcome of interest was couple testing (yes/no) after receipt of a CVCT invitation. INA, couple and invitation characteristics predictive of couples’ testing were evaluated accounting for two-level clustering. Results INAs delivered invitations resulting in 1727 couples testing (6% success rate). In multivariate analyses, INA characteristics significantly predictive of CVCT uptake included promoting in community-based (adjusted OR (aOR)=1.3; 95% CI 1.0 to 1.8) or health (aOR=1.5; 95% CI 1.2 to 2.0) networks versus private networks; being employed in the sales/service industry (aOR=1.5; 95% CI 1.0 to 2.1) versus unskilled manual labour; owning a home (aOR=0.7; 95% CI 0.6 to 0.9) versus not; and having tested for HIV with a partner (aOR=1.4; 95% CI 1.1 to 1.7) or alone (aOR=1.3; 95% CI 1.0 to 1.6) versus never having tested. Cohabiting couples were more likely to test (aOR=1.4; 95% CI 1.2 to 1.6) than non-cohabiting couples. Context characteristics predictive of CVCT uptake included inviting couples (aOR=1.2; 95% CI 1.0 to 1.4) versus individuals; the woman (aOR=1.6; 95% CI 1.2 to 2.2) or couple (aOR=1.4; 95% CI 1.0 to 1.8) initiating contact versus the INA; the couple being socially acquainted with the INA (aOR=1.6; 95% CI 1.4 to 1.9) versus having just met; home invitation delivery (aOR=1.3; 95% CI 1.1 to 1.5) versus elsewhere; and easy invitation delivery (aOR=1.8; 95% CI 1.4 to 2.2) versus difficult as reported by the INA. Conclusions This study demonstrated the ability of influential people to promote CVCT and identified agent, couple and context-level factors associated with CVCT uptake in Lusaka, Zambia. We encourage the development of CVCT promotions in other sub-Saharan African countries to support sustained CVCT dissemination.

A Randomized Controlled Trial to Promote Long-Term Contraceptive Use Among HIV-Serodiscordant and Concordant Positive Couples in Zambia.

BACKGROUND Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs). METHODS This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia. RESULTS Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods. CONCLUSIONS Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.

The Relationship Between Alcohol Consumption and Unprotected Sex Among Known HIV-discordant Couples in Rwanda and Zambia

Although alcohol abuse is highly prevalent in many countries in sub-Saharan Africa, little is known about the relationship between alcohol consumption and risky sexual behavior in these settings. An understanding of this relationship is particularly important given the high prevalence of HIV that exists in many of these countries. This study analyzes data collected from members of cohabiting HIV-discordant couples regarding alcohol consumption and self-reported condom use. After controlling for demographic and socioeconomic co-factors, alcohol use by male partners of HIV-discordant couples was associated with self-reported unprotected sex at follow-up. Counseling about alcohol use should be part of HIV testing and counseling programs, particularly among those found to be HIV-positive.

Influence network effectiveness in promoting couples HIV voluntary counseling and testing in Kigali Rwanda.

Objective:To identify predictors of promotion of couples’ HIV voluntary counseling and testing (CVCT) in Kigali, Rwanda. Design:Analysis of CVCT promotional agent [influential network leaders (INLs), influential network agents (INAs)], and couple/invitation-level predictors of CVCT uptake. Methods:Number of invitations and couples tested were evaluated by INL, INA, and couple/contextual factors. Multivariable logistic regression accounting for two-level clustering analyzed factors predictive of couples’ testing. Results:Twenty-six INLs recruited and mentored 118 INAs who delivered 24 991 invitations. 4513 couples sought CVCT services after invitation. INAs distributed an average of 212 invitations resulting in an average of 38 couples tested/agent. Characteristics predictive of CVCT in multivariate analyses included the invitee and INA being socially acquainted [adjusted odds ratio (aOR) = 1.4; 95% confidence interval (CI) 1.2–1.6]; invitations delivered after public endorsement (aOR = 1.3; 95% CI 1.1–1.5); and presence of a mobile testing unit (aOR = 1.4; 95% CI 1.0–2.0). In stratified analyses, predictors significant among cohabiting couples included invitation delivery to the couple (aOR = 1.2; 95% CI 1.0–1.4) and in the home (aOR = 1.3; 95% CI 1.1–1.4), whereas among noncohabiting couples, predictors included invitations given by unemployed INAs (aOR = 1.7; 95% CI 1.1–2.7). Cohabiting couples with older men were more likely to test, whereas younger age was associated with testing among men in noncohabiting unions. Conclusions:Invitations distributed by influential people were successful in prompting couples to seek joint HIV testing, particularly if the invitation was given in the home to someone known to the INA and accompanied by a public endorsement of CVCT. Mobile units also increased the number of couples tested. Country-specific strategies to promote CVCT programs are needed to reduce HIV transmission among those at highest risk for HIV in sub-Saharan Africa.

Fertility goal-based counseling increases contraceptive implant and IUD use in HIV-discordant couples in Rwanda and Zambia.

BACKGROUND HIV-discordant heterosexual couples are faced with the dual challenge of preventing sexual HIV transmission and unplanned pregnancies with the attendant risk of perinatal HIV transmission. Our aim was to examine uptake of two long-acting reversible contraceptive (LARC) methods--intrauterine devices (IUD) and hormonal implants--among HIV-discordant couples in Rwanda and Zambia. STUDY DESIGN Women were interviewed alone or with their partner during routine cohort study follow-up visits to ascertain fertility goals; those not pregnant, not infertile, not already using LARC, and wishing to limit or delay fertility for ≥3 years were counseled on LARC methods and offered an IUD or implant on-site. RESULTS Among 409 fertile HIV-discordant Rwandan women interviewed (126 alone, 283 with partners), 365 (89%) were counseled about LARC methods, and 130 (36%) adopted a method (100 implant, 30 IUD). Of 787 fertile Zambian women interviewed (457 alone, 330 with partners), 528 (67%) received LARC counseling, of whom 177 (34%) adopted a method (139 implant, 38 IUD). In both countries, a womans younger age was predictive of LARC uptake. LARC users reported fewer episodes of unprotected sex than couples using only condoms. CONCLUSIONS Integrated fertility goal-based family planning counseling and access to LARC methods with reinforcement of dual-method use prompted uptake of IUDs and implants and reduced unprotected sex among HIV-discordant couples in two African capital cities.

Impact of long-term contraceptive promotion on incident pregnancy: a randomized controlled trial among HIV positive couples in Lusaka, Zambia

Objectives:To evaluate the impact of family planning promotion on incident pregnancy in a combined effort to address Prongs 1 and 2 of prevention of mother-to-child transmission of HIV. Design:We conducted a factorial randomized controlled trial of 2 video-based interventions. Methods:“Methods” and “Motivational” messages promoted long-term contraceptive use among 1060 couples with HIV in Lusaka, Zambia. Results:Among couples not using contraception before randomization (n = 782), the video interventions had no impact on incident pregnancy. Among baseline contraceptive users, viewing the “Methods video” which focused on the intrauterine device and contraceptive implant was associated with a significantly lower pregnancy incidence [hazard ratio (HR) = 0.38; 95% confidence interval (CI): 0.19 to 0.75] relative to those viewing control and/or motivational videos. The effect was strongest in concordant positive couples (HR = 0.22; 95% CI: 0.08 to 0.58) and couples with HIV-positive women (HR = 0.23; 95% CI: 0.09 to 0.55). Conclusions:The “Methods video” intervention was previously shown to increase uptake of long-acting contraception and to prompt a shift from daily oral contraceptives to quarterly injectables and long-acting methods such as the intrauterine device and implant. Follow-up confirms sustained intervention impact on pregnancy incidence among baseline contraceptive users, in particular couples with HIV-positive women. Further work is needed to identify effective interventions to promote long-acting contraception among couples who have not yet adopted modern methods.

Syphilis Treatment Response Among HIV-Discordant Couples in Zambia and Rwanda

BACKGROUND Syphilis continues to be a common sexually transmitted infection, despite the availability of inexpensive and effective treatment. Infection in human immunodeficiency virus (HIV)-discordant couples is important because syphilis increases the risk of HIV acquisition. Current US treatment guidelines recommend 1 dose of benzathine penicillin for early syphilis, irrespective of HIV status, but data from coinfected patients are limited. METHODS Retrospective analysis of 1321 individuals in 2 African HIV-discordant couple cohorts was performed. Cox proportional hazards analysis and multivariable modeling were used to assess predictors of serologic response to treatment at 180 days and 400 days. Modeling was performed for all episodes of positive rapid plasma reagin (RPR) test results and on a subset with higher RPR titers (≥1:4). RESULTS A total of 1810 episodes of syphilis among 1321 individuals were treated with penicillin between 2002 and 2008. Although a positive RPR was more common in the HIV-infected partners, HIV infection did not impact the likelihood of serologic response to therapy (odds ratio [OR], 1.001; P = .995). By 400 days, 67% had responded to therapy, 27% were serofast, and 6.5% had documented reinfection. Prevalent infections were more likely to remain serofast than incident infections (33% vs 20% at 400 days). CONCLUSIONS In 2 HIV-serodiscordant couple cohorts in Africa, incident syphilis had a very good likelihood of response to penicillin therapy, irrespective of HIV infection. This supports current Centers for Disease Control and Prevention treatment guidelines. A high proportion of prevalent RPR-positive infections remain serofast despite treatment.