Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.

BACKGROUND: The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE. METHODS: In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50. FINDINGS: Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines. INTERPRETATION: HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. FUNDING: The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results.

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .

Prevalence and correlates of condom use at last sexual intercourse pre- and post-COVID-19 lockdown among adolescent girls and young women in central and western Kenya.

We investigated condom use at last sexual intercourse among adolescent girls and young women (AGYW) to determine the prevalence and correlates of condom use pre- and post-COVID-19 lockdown. Condom use was compared pre- and post-COVID-19 lockdown using a single group interrupted time series analysis. Multivariable Poisson regression was used to determine the correlates of condom use at last sexual intercourse. We found a statistically significant decrease in prevalence of condom use at last sexual intercourse post-COVID-19 lockdown. Condom use at last sexual intercourse was associated with younger age, current contraceptive use, and higher education. AGYW in concurrent relationships were less likely to use condoms, as were owners of mobile phones. These findings suggest a disconnect between youth knowledge of HIV prevention and their actual condom use, particularly in concurrent sexual partnerships. Future research should explore how dynamic fertility intentions, mobile phone access, concurrent sexual partnerships and empowerment influence condom use among sub-Saharan AGYW.

HPV vaccination in Kenya: a study protocol to assess stakeholders' perspectives on implementation drivers of HPV vaccination and the acceptability of the reduced dose strategy among providers.

Background: Cervical cancer is the leading cause of cancer-related deaths among Kenyan women. Persistent infection with high-risk oncogenic Human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. HPV vaccines are safe, durable, and efficacious in preventing incident HPV infections. In Kenya, despite efforts to increase HPV vaccination, coverage remains low. We sought to assess: (1) barriers and facilitators of HPV vaccination from the perspective of adolescent girls and young women (AGYW), their guardians as well as stakeholders involved in HPV vaccine delivery, and (2) the acceptability of the single dose of the HPV vaccination among healthcare providers (HCPs). Methods: Our study is nested within the KENya Single-dose HPV-vaccine Efficacy study (KEN SHE) that sought to test the efficacy of single-dose bivalent (HPV 16/18) and single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination. We are conducting this study in Kiambu, Nairobi, and Kisumu counties. In these counties, we are interviewing stakeholders (n = ∼25), selected based on their role in HPV vaccination at the county and national levels. Interviews are audio recorded and conducted in English or Swahili. The semi-structured interview guides were designed based on: (1) the Theoretical Domains Framework (TDF) for AGYW and guardians and (2) the Consolidated Framework for Implementation Research (CFIR) for other stakeholders. The Theoretical Framework of Acceptability (TFA) was leveraged to design the survey administered to HCPs (n = ∼309) involved in HPV vaccination. We will develop a codebook based on emerging codes from the transcripts and constructs from the TDF and CFIR. Emerging themes will be summarized highlighting similarities and differences between and within the different stakeholder groups and counties. Descriptive statistics and a χ2 test will be used to assess the distribution of responses between the different sites and regression analysis will be used to assess factors associated with high acceptability of the single-dose strategy while controlling for confounding variables. Discussion: Our study will describe key barriers and facilitators that affect HPV vaccination from the perspective of multiple stakeholders as well as insights on the perspective of HCPs towards the single-dose strategy to inform the designing of strategies to increase HPV vaccination uptake in Kenya and comparable settings.

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya.

Introduction: Globally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies. Methods: Healthy women ages 18-34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition. Results: Among 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36-90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and -27.1% to -20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively). Conclusion: TFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. Clinical Trial Registration: NCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382].

Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya.

In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18-34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of Candida spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log100.57 and log100.27 decrease respectively; p > 0.05). The TFV/LNG IVR was more 'stabilizing': 50% of the participants' microbiota community state types remained unchanged and 50% shifted towards higher Lactobacillus abundance. Specifically, TFV/LNG IVR use was accompanied by increased abundances of Lactobacillus gasseri/hominis/johnsonii/taiwanensis (16.3-fold) and L. fermentum/reuteri/vaginalis (7.0-fold; all p < 0.01). A significant shift in the overall microbial α-diversity or ß-diversity was not observed for either IVR, and IVR use did not influence Candida spp. prevalence. TFV/LNG and TFV IVRs did not adversely affect the genital microbiota and are safe to use. Our findings support further studies assessing their efficacy in preventing HIV/HSV-2 and unintended pregnancies.

Efficacy of single-dose HPV vaccination among young African women.

Background: Single-dose HPV vaccination, if efficacious, would be tremendously advantageous; simplifying implementation and decreasing costs. Methods: We performed a randomized, multi-center, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) or bivalent (HPV 16/18) HPV vaccination compared to meningococcal vaccination among Kenyan women aged 15-20 years. Enrollment and six monthly cervical swabs and a month three vaginal swab were tested for HPV DNA. Enrollment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who tested HPV antibody negative at enrollment and HPV DNA negative at enrollment and month three. The primary outcome was incident persistent vaccine-type HPV infection by month 18. Results: Between December 2018 and June 2021, 2,275 women were randomly assigned and followed; 758 received the nonavalent HPV vaccine, 760 the bivalent HPV vaccine, and 757 the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group; nonavalent Vaccine Efficacy (VE) was 97.5% (95%CI 81.7-99.7%, p=<0.0001), and bivalent VE was 97.5% (95%CI 81.6-99.7%, p=<0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group; nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95%CI 68.5-96.1%, p<0.0001). The rate of SAEs was 4.5-5.2% by group. Conclusions: Over the 18 month time-frame we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens.

Impact of catch-up human papillomavirus vaccination on cervical cancer incidence in Kenya: A mathematical modeling evaluation of HPV vaccination strategies in the context of moderate HIV prevalence.

BACKGROUND: Cervical cancer incidence is high in Kenya due to HIV and limited access to cancer prevention services. Human papillomavirus (HPV) has been shown to increase HIV acquisition; however, the potential impact of HPV vaccination on HIV is unknown. We modeled the health impact of HPV vaccination in the context of the HIV epidemiology in Kenya. METHODS: Using a validated compartmental transmission model of HIV and HPV set in Kenya, we evaluated five scenarios of nonavalent HPV vaccination: single-age-vaccination of 10-year-old girls at 90% coverage; multi-age-cohort (MAC) vaccination of 10-14-year-old girls at 90% coverage; MAC plus moderate-coverage (50%) catch-up vaccination of 15-24-year-old women; MAC plus high-coverage (80%) catch-up of 15-24-year-old women; and MAC plus catch-up of 15-44-year-old women at 80% coverage (HPV-FASTER). We compared cervical cancer incidence, HIV prevalence, and cumulative cervical cancer and HIV cases averted after 50 years to a baseline scenario without vaccination. In all scenarios, we assumed the UNAIDS 90-90-90 goal for HIV treatment is attained by 2030. FINDINGS: In 2021, model-estimated cervical cancer incidence is 44/100,000 and HIV prevalence among women is 6·5%. In 2070, projected cancer incidence declines to 27/100,000 and HIV prevalence reaches 0·3% without vaccination. With single-age-vaccination, cancer incidence in 2070 is reduced by 68%, averting 64,529 cumulative cancer cases. MAC vaccination reduces cancer incidence by 75%, averting 206,115 cancer cases. Moderate and high-coverage catch-up and HPV-FASTER reduce cancer incidence by 80%, 82%, and 84%, averting 254,930, 278,690, and 326,968 cancer cases, respectively. In all scenarios, HIV prevalence in 2070 is reduced by a relative 8-11%, with 15,609-34,981 HIV cases averted after 50 years. INTERPRETATION: HPV vaccination can substantially reduce cervical cancer incidence in Kenya in the next 50 years, particularly if women up to age 24 are vaccinated. HIV treatment scale-up can also alleviate cervical cancer burden. However, HPV vaccination has modest additional impact on HIV when antiretroviral therapy coverage is high. FUNDING: National Institutes of Health, Bill and Melinda Gates Foundation.

The Kanyakla study: Randomized controlled trial of a microclinic social network intervention for promoting engagement and retention in HIV care in rural western Kenya.

BACKGROUND: Existing social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness. METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits ('time-in-care'). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma. RESULTS: Of 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61-1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08-0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2-0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17). CONCLUSIONS: The data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care. TRIAL REGISTRATION: Clinical trial number: NCT02474992.

Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial.

BACKGROUND: HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. METHODS: We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15-20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. DISCUSSION: This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03675256 . Registered on September 18, 2018.

Empowering HIV-infected women in low-resource settings: A pilot study evaluating a patient-centered HIV prevention strategy for reproduction in Kisumu, Kenya.

BACKGROUND: Female positive/male negative HIV-serodiscordant couples express a desire for children and may engage in condomless sex to become pregnant. Current guidelines recommend antiretroviral treatment in HIV-serodiscordant couples, yet HIV RNA viral suppression may not be routinely assessed or guaranteed and pre-exposure prophylaxis may not be readily available. Therefore, options for becoming pregnant while limiting HIV transmission should be offered and accessible to HIV-affected couples desiring children. METHODS: A prospective pilot study of female positive/male negative HIV-serodiscordant couples desiring children was conducted to evaluate the acceptability, feasibility, and effectiveness of timed vaginal insemination. Eligible women were 18-34 years with regular menses. Prior to timed vaginal insemination, couples were observed for two months, and tested and treated for sexually transmitted infections. Timed vaginal insemination was performed for up to six menstrual cycles. A fertility evaluation and HIV RNA viral load assessment was offered to couples who did not become pregnant. FINDINGS: Forty female positive/male negative HIV-serodiscordant couples were enrolled; 17 (42.5%) exited prior to timed vaginal insemination. Twenty-three couples (57.5%) were introduced to timed vaginal insemination; eight (34.8%) achieved pregnancy, and six live births resulted without a case of HIV transmission. Seven couples completed a fertility evaluation. Four women had no demonstrable tubal patency bilaterally; one male partner had decreased sperm motility. Five women had unilateral/bilateral tubal patency; and seven women had an HIV RNA viral load (≥ 400 copies/mL). CONCLUSION: Timed vaginal insemination is an acceptable, feasible, and effective method for attempting pregnancy. Given the desire for children and inadequate viral suppression, interventions to support safely becoming pregnant should be integrated into HIV prevention programs.

A Novel Safer Conception Counseling Toolkit for the Prevention of HIV: A Mixed-Methods Evaluation in Kisumu, Kenya.

Safer conception strategies can prevent HIV transmission between HIV-discordant partners while allowing them to conceive. However, HIV care providers in sub-Saharan Africa report they are not trained in safer conception, and patients are not routinely offered safer conception services. This mixed-methods pilot study evaluated the impact, acceptability, and feasibility of a novel Safer Conception Counseling Toolkit among providers and patients in Kenya. We enrolled 20 HIV-positive women, 10 HIV-discordant couples, and 10 providers from HIV care and treatment clinics. Providers completed questionnaires before/after training, and then counseled HIV-affected patients. Change in patient knowledge was assessed before/after counseling. Qualitative interviews were conducted among providers and patients. The Toolkit was associated with large, significant increases in patient knowledge, and provider confidence, knowledge, and favorable attitudes toward safer conception counseling; 20% felt confident before versus 100% after training (p < 0.01).

Movement between facilities for HIV care among a mobile population in Kenya: transfer, loss to follow-up, and reengagement.

HIV treatment is life-long, yet many patients travel or migrate for their livelihoods, risking treatment interruption. We examine timely reengagement in care among patients who transferred-out or were lost-to-follow-up (LTFU) from a rural HIV facility. We conducted a cohort study among 369 adult patients on antiretroviral therapy between November 2011 and November 2013 on Mfangano Island, Kenya. Patients who transferred or were LTFU (i.e., missed a scheduled appointment by ≥90 days) were traced to determine if they reengaged or accessed care at another clinic. We report cumulative incidence and time to reengagement using Cox proportional hazards models adjusted for patient demographic and clinical characteristics. Among 369 patients at the clinic, 23(6%) requested an official transfer and 78(21%) were LTFU. Among official transfers, cumulative incidence of linkage to their destination facility was 91% at three months (95%CI (confidence intervals) 69-98%). Among LTFU, cumulative incidence of reengagement in care at the original or a new clinic was 14% at three months (95%CI 7-23%) and 60% at six months (95%CI 48-69%). In the adjusted Cox model, patients who left with an official transfer reengaged in care six times faster than those who did not (adjusted hazard ratio 6.2, 95%CI 3.4-11.0). Patients who left an island-based HIV clinic in Kenya with an official transfer letter reengaged in care faster than those who were LTFU, although many in both groups had treatment gaps long enough to risk viral rebound. Better coordination of transfers between clinics, such as assisting patients with navigating the process or improving inter-clinic communication surrounding transfers, may reduce delays in treatment during transfer and improve overall clinical outcomes.

Perspectives of healthcare providers and HIV-affected individuals and couples during the development of a Safer Conception Counseling Toolkit in Kenya: stigma, fears, and recommendations for the delivery of services.

Reproduction is important to many HIV-affected individuals and couples and healthcare providers (HCPs) are responsible for providing resources to help them safely conceive while minimizing the risk of sexual and perinatal HIV transmission. In order to fulfill their reproductive goals, HIV-affected individuals and their partners need access to information regarding safer methods of conception. The objective of this qualitative study was to develop a Safer Conception Counseling Toolkit that can be used to train HCPs and counsel HIV-affected individuals and couples in HIV care and treatment clinics in Kenya. We conducted a two-phased qualitative study among HCPs and HIV-affected individuals and couples from eight HIV care and treatment sites in Kisumu, Kenya. We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) to assess the perspectives of HCPs and HIV-affected individuals and couples in order to develop and refine the content of the Toolkit. Subsequently, IDIs were conducted among HCPs who were trained using the Toolkit and FGDs among HIV-affected individuals and couples who were counseled with the Toolkit. HIV-related stigma, fears, and recommendations for delivery of safer conception counseling were assessed during the discussions. One hundred and six individuals participated in FGDs and IDIs; 29 HCPs, 49 HIV-affected women and men, and 14 HIV-serodiscordant couples. Participants indicated that a safer conception counseling and training program for HCPs is needed and that routine provision of safer conception counseling may promote maternal and child health by enhancing reproductive autonomy among HIV-affected couples. They also reported that the Toolkit may help dispel the stigma and fears associated with reproduction in HIV-affected couples, while supporting them in achieving their reproductive goals. Additional research is needed to evaluate the Safer Conception Toolkit in order to support its implementation and use in HIV care and treatment programs in Kenya and other HIV endemic regions of sub-Saharan Africa.

Cervical Cancer Stigma in Rural Kenya: What Does HIV Have to Do with It?

Cervical cancer is a leading cause of cancer-related death amongst women in sub-Saharan Africa, largely due to the lack of early screening and treatment. In addition to poor access to screening services, inadequate uptake of available services is a barrier to early identification of precancerous lesions. Given that cervical cancer is caused by a sexually transmitted virus and is associated with HIV positivity, stigma is one of the potential barriers to the utilization of cervical cancer programs in sub-Saharan Africa. We conducted a cross-sectional survey of 419 women attending health facilities in rural western Kenya to measure levels of cervical cancer and HIV stigma and to measure the associations between cervical cancer stigma, HIV stigma, and HIV status. Women who qualified for cervical cancer screening were asked to complete an oral questionnaire using a modified 9-point HIV stigma scale. Low cervical cancer stigma was reported in this study, with only 85/419 (20.3 %) of respondents answering yes to at least one cervical cancer stigma question. However, cervical cancer stigma was highly correlated with HIV stigma (correlation coefficient 0.72) and was significantly lower in HIV-positive women (p < 0.001). Reducing cervical cancer stigma in the general population is an important part of promoting screening in sub-Saharan Africa.

The feasibility, time savings and economic impact of a designated time appointment system at a busy HIV care clinic in Kenya: a randomized controlled trial.

INTRODUCTION: As efforts are made to reach universal access to ART in Kenya, the problem of congestion at HIV care clinics is likely to worsen. We evaluated the feasibility and the economic benefits of a designated time appointment system as a solution to decongest HIV care clinics. METHODS: This was an explanatory two-arm open-label randomized controlled trial that enrolled 354 consenting participants during their normal clinic days and followed-up at subsequent clinic appointments for up to nine months. Intervention arm participants were given specific dates and times to arrive at the clinic for their next appointment while those in the control arm were only given the date and had the discretion to decide on the time to arrive as is the standard practice. At follow-up visits, we recorded arrival and departure times and asked the monetary value of work participants engaged in before and after clinic. We conducted multiple imputation to replace missing data in our primary outcome variables to allow for intention-to-treat analysis; and analyzed the data using Mann-Whitney U test. RESULTS: Overall, 72.1% of the intervention participants arrived on time, 13.3% arrived ahead of time and 14.6% arrived past scheduled time. Intervention arm participants spent a median of 65 [interquartile range (IQR), 52-87] minutes at the clinic compared to 197 (IQR, 173-225) minutes for control participants (p<0.01). Furthermore, intervention arm participants were more productively engaged on their clinic days valuing their cumulative work at a median of USD 10.5 (IQR, 60.0-16.8) compared to participants enrolled in the control arm who valued their work at USD 8.3 (IQR, 5.5-12.9; p=0.02). CONCLUSIONS: A designated time appointment system is feasible and provides substantial time savings associated with greater economic productivity for HIV patients attending a busy HIV care clinic.

Community perceptions of childbearing and use of safer conception strategies among HIV-discordant couples in Kisumu, Kenya.

INTRODUCTION: Safer conception strategies (SCS) have the potential to decrease HIV transmission among HIV-discordant couples who desire children. Community perceptions of SCS may influence the scale-up and uptake of these services, but little is known about how communities will react to these strategies. Without community support for SCS, their success as an HIV prevention tool may be limited. The objective of this study is to characterize community perceptions of SCS for HIV-discordant couples in Kisumu, Kenya, to inform ongoing and future safer conception intervention studies in low-resource settings. METHODS: We conducted six focus group discussions and 11 in-depth-interviews in Kisumu, Kenya, among a diverse group (N=59) of community members, including men, women, youth (age 19-25), community health workers and local leaders. An iterative qualitative analysis using a grounded theory approach was employed. RESULTS AND DISCUSSION: All participants emphasized the importance of childbearing in their society and the right to have children, regardless of an individual's HIV status. While most participants believed that HIV-discordant couples should be allowed to have children, they discussed several barriers to the uptake of SCS such as HIV-related stigma, fear of HIV transmission to the uninfected partner and child, fear of unfamiliar medical procedures and lack of information among community members and health care providers about HIV prevention interventions that allow safer conception. Access to information, community experiences with successful safer conception interventions, healthcare provider training, male engagement and community mobilization may help overcome these barriers. Though assisted reproduction strategies generated the most negative reactions from participants, our results suggest that with education and explanation of these services, participants express interest in these strategies and want them to be offered in their community. CONCLUSIONS: Many community members noted a need and desire for safer conception education and services in Kisumu. However, community barriers such as fear, stigma and lack of information should be addressed before safer conception interventions can be successfully implemented and delivered. Further research focused on community education, male engagement and healthcare provider training is a crucial next step in delivering safer conception in this region.

Implementation and Operational Research: Pulling the Network Together: Quasiexperimental Trial of a Patient-Defined Support Network Intervention for Promoting Engagement in HIV Care and Medication Adherence on Mfangano Island, Kenya.

BACKGROUND: Despite progress in the global scale-up of antiretroviral therapy, sustained engagement in HIV care remains challenging. Social capital is an important factor for sustained engagement, but interventions designed to harness this powerful social force are uncommon. METHODS: We conducted a quasiexperimental study evaluating the impact of the Microclinic Social Network intervention on engagement in HIV care and medication adherence on Mfangano Island, Kenya. The intervention was introduced into 1 of 4 similar communities served by this clinic; comparisons were made between communities using an intention-to-treat analysis. Microclinics, composed of patient-defined support networks, participated in 10 biweekly discussion sessions covering topics ranging from HIV biology to group support and group HIV status disclosure. Nevirapine concentrations in hair were measured before and after study. RESULTS: One hundred thirteen (74%) intervention community participants joined a microclinic group, 86% of whom participated in group HIV status disclosure. Over 22-month follow-up, intervention community participants experienced one-half the rate of ≥ 90-day clinic absence as those in control communities (adjusted hazard ratio: 0.48; 95% confidence interval: 0.25 to 0.92). Nevirapine hair levels declined in both study arms; in adjusted linear regression analysis, the decline was 6.7 ng/mg less severe in the intervention arm than control arm (95% confidence interval: -2.7 to 16.1). CONCLUSIONS: The microclinic intervention is a promising and feasible community-based strategy to improve long-term engagement in HIV care and possibly medication adherence. Reducing treatment interruptions using a social network approach has important implications for individual patient virologic suppression, morbidity, and mortality and for broader community empowerment and engagement in healthcare.

Changing knowledge, attitudes, and behaviors regarding cervical cancer screening: The effects of an educational intervention in rural Kenya.

OBJECTIVE: Cervical cancer screening uptake may be influenced by inadequate knowledge in resource-limited settings. This randomized trial evaluated a health talk's impact on cervical cancer knowledge, attitudes, and screening rates in rural Kenya. METHODS: 419 women attending government clinics were randomized to an intervention (N=207) or control (N=212) group. The intervention was a brief health talk on cervical cancer. Participants completed surveys at enrollment (all), immediately after the talk (intervention arm), and at three-months follow-up (all). The primary outcomes were the change in knowledge scores and the final screening rates at three-months follow-up. Secondary outcomes were changes in awareness about cervical cancer screening, perception of personal cervical cancer risk, cervical cancer and HIV stigma, and screening acceptability. RESULTS: Mean Knowledge Scores increased by 26.4% (8.7 points increased to 11.0 points) in the intervention arm compared to only 17.6% (8.5 points increased to 10.0 points) in the control arm (p<0.01). Screening uptake was moderate in both the intervention (58.9%; N=122) and control (60.9%; N=129) arms, with no difference between the groups (p=0.60). CONCLUSION: A brief health talk increased cervical cancer knowledge, although it did not increase screening over simply informing women about free screening. PRACTICAL IMPLICATIONS: Screening programs can increase patient understanding with just a brief educational intervention.