Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. METHODS: Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. RESULTS: In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45-1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74-1.75). CONCLUSIONS: The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA's implementation with significant disruptions in FP care delivery during the trial. While SAIA's data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.

Impact of Human Immunodeficiency Virus and Peripartum Period on Mycobacterium tuberculosis Infection Detection.

BACKGROUND: Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST). METHODS: Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP). RESULTS: 400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24-30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P < .001), driven primarily by QFT-Plus-positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04-2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus-positive participants in pregnancy, Mycobacterium tuberculosis  (Mtb)-specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points. CONCLUSIONS: QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb-specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.

The Association Between Adverse Childhood Experiences and Human Papillomavirus Vaccination Coverage in US Young Adults: A Cross-Sectional Study.

BACKGROUND: Adverse childhood experiences (ACEs) contribute to adverse health outcomes in adulthood. Access to preventive health care services, including genital human papillomavirus (HPV) vaccinations, may mitigate the impact of ACEs on adverse health outcomes. Our objective was to assess associations between ACEs and HPV vaccination coverage among young adults. METHODS: We included 3415 respondents aged 18 to 29 years to the 2019-2020 Behavioral Risk Factor Surveillance System ACE and HPV vaccination modules. Adverse childhood experiences included emotional, physical, and sexual abuse; household intimate partner violence, substance abuse, and mental illness; and parental separation/divorce and incarcerated household member. We used log-binomial regression models to calculate prevalence ratios (PRs) with 95% confidence intervals (CI) for associations between ACEs and self-reported HPV vaccination and completion. Secondary outcomes included influenza vaccination uptake, time since routine checkup, HIV testing history, and HIV-related risk behavior. RESULTS: Several ACEs were positively associated with HPV vaccination initiation, including emotional abuse (PR, 1.29; 95% CI, 1.17-1.43), intimate partner violence (PR, 1.14; 95% CI, 1.00-1.30), substance abuse (PR, 1.20; 95% CI, 1.08-1.33), and mental illness (PR, 1.35; 95% CI, 1.22-1.50). Similar associations were observed for completion. Conversely, most ACEs were negatively associated with influenza vaccination (PRs from 0.72 to 1.00) and with recent checkup (PRs from 0.92 to 1.00). Adverse childhood experiences were positively associated with having had an HIV test (PRs from 1.19 to 1.56) and HIV-related risk behavior (PRs from 1.19 to 2.07). CONCLUSIONS: The unexpected positive associations between ACEs and HPV vaccination coverage could be due to opportunities to receive HPV vaccination in late adolescence or early adulthood while accessing STI/HIV prevention or treatment services. Future studies should evaluate associations between ACEs and timely HPV vaccination in early adolescence.

Fertility Desire and Associations with Condomless Sex, Antiretroviral Adherence, and Transmission Potential in a Cohort of Kenyan Women Living with HIV in Sero-discordant Relationships: A Mixed Methods Study.

For women living with HIV (WLH) in serodiscordant partnerships, decisions about childbearing can challenge condom use and antiretroviral adherence. In a prospective cohort of 148 WLH in serodiscordant partnerships, 58 (39%) wanted more children in the future but were not currently trying to conceive (fertility desire), and 32 (22%) were currently trying to become pregnant (fertility intent). Detection of prostate specific antigen (PSA) in vaginal secretions, a marker for recent condomless sex, was lowest in women with fertility desire and highest in women with fertility intent. Detectable viral load followed a similar pattern. Risk of HIV transmission, when condomless sex and PSA detection occurred concurrently, was three to fourfold higher at visits with fertility intent compared to visits with fertility desire. Qualitative interviews underscored the importance women place on childbearing and suggested that they had limited information about the role of antiretroviral therapy in reducing sexual HIV transmission.

A cross-sectional study of the prevalence, barriers, and facilitators of cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya. METHODS: Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening. RESULTS: A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2-6) with a median of 1 provider trained to perform screening (IQR 0-3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05-2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI 1.82-7.83). CONCLUSION: Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.

Transition to independent care for youth living with HIV: a cluster randomised clinical trial.

BACKGROUND: Transitioning youth living with HIV to adult care is a crucial step in the HIV care continuum; however, tools to support transition in sub-Saharan Africa are insufficient. We assessed the effectiveness of an adolescent transition package (ATP) to improve youth readiness for transition to independent HIV care. METHODS: In this hybrid type 1, multicentre, cluster randomised clinical trial, we assessed the effectiveness of an ATP (administered by routine clinic staff, which included standardised assessments and chapter books to guide discussions at scheduled clinic visits) in four counties in Kenya, with HIV clinics randomly assigned 1:1 to ATP or control (standard-of-care practice). Clinics were eligible to participate if they had at least 50 youth (aged 10-24 years) living with HIV enrolled in care. We used restricted randomisation to achieve cluster balance and an independent biostatistician used computer-generated random numbers to assign clinics. We excluded very large clinics with more than 1000 youth, clinics with fewer than 50 youth, paediatric-only clinics, clinics with logistical challenges, and the smallest clinics in Homa Bay county. Youth were eligible for the transition intervention if they were enrolled in participating clinics, were aged 15-24 years, and were aware of their positive HIV diagnosis. Study staff assessed transition readiness scores overall and by four domains (HIV literacy, self-management, communication, and support) in youth with HIV, which were then compared between groups by use of mixed-effects linear regression models. Analysis was by intention-to-treat and was adjusted for multiple comparisons. This trial is registered with ClinicalTrials.gov, NCT03574129. FINDINGS: We identified 35 clinics in four counties; of these, ten were assigned to the intervention group and ten to the control group. Of 1066 youth with HIV enrolled between Nov 1, 2019, and March 18, 2020, 578 (54%) were in intervention and 488 (46%) in control sites. Mean baseline transition readiness score was 12·1 (SD 3·4) in ATP sites and 11·4 (3·7) in control sites. At 1 year, adjusting for baseline scores, age, and months since HIV disclosure, participants in the ATP group had significantly higher overall transition readiness scores (adjusted mean difference 1·7, 95% CI 0·3-3·1, p=0·024), and higher scores in HIV literacy domain (adjusted mean difference 1·0, 0·2-1·7, p=0·011). At 12 months, 15 serious adverse events were recorded, none of which were thought to be related to study participation. INTERPRETATION: Integrating ATP approaches could enhance long-term HIV care in youth with HIV as they age into adulthood. FUNDING: US National Institutes of Health.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Cumulative Mycobacterium tuberculosis Infection Incidence (Measured Primarily by Tuberculin Skin Test) Among Infants With Human Immunodeficiency Virus Exposure: Observational Follow-up of an Isoniazid Prophylaxis Trial.

Cumulative 24-month Mycobacterium tuberculosis infection incidence (measured primarily by tuberculin skin test [TST]) was high among human immunodeficiency virus exposed but uninfected infants (8.7 [95% confidence interval, 6.3-11.9] per 100 person-years). Trend for decreased TST positivity among infants at trial end (12 months postenrollment) randomized to isoniazid at 6 weeks of age was not sustained through observational follow-up to 24 months of age. CLINICAL TRIALS REGISTRATION: NCT02613169.

Cervical cancer screening, abnormal results, and follow-up in women with substance use-related diagnoses.

Background: Substance use-related diagnoses are common and associated with poor health outcomes. The objective of this analysis was to compare rates of cervical cancer screening, screening abnormalities, and follow-up care in women with and without a substance use-related diagnosis seen for primary care between January 1, 2016 and December 31, 2019 in the University of Washington healthcare system. Methods: This study included women aged 21-65 years of age who had at least one outpatient visit between January 1, 2016 and December 31, 2019 within one of 45 primary care or women's health clinics in the academic healthcare system. Exposure status was defined using ICD10 codes for substance-use related diagnoses or no substance-use related diagnoses. Only first cervical cancer screening was included. Generalized linear models with a binomial family and log link were used to estimate risk ratios. Results: 3845 women had a substance use-related diagnosis and 89214 did not. Women with a substance use-related diagnosis were less likely to be screened for cervical cancer (44%, 1675/3845) compared to women without a substance use-related diagnosis (49%, 43338/89214; relative risk [RR] 0.90, 95% CI 0.86-0.93). Women with a substance use-related diagnosis were also more likely to have an abnormal screening result (18%, 304/1675) compared to women without a substance use-related diagnosis (10%, 4528/43338; RR 1.74, 95% CI 1.56-1.93). Follow-up for abnormal screens did not differ significantly between groups (24 vs 25%; RR 0.80, 95% CI 0.55-1.17). Conclusion: To combat disparities in cervical cancer screening for women with substance use-related diagnoses, public health efforts should expand access to screening where women with substance use-related diagnoses are seen, including acute care, inpatient hospitalizations, and addiction treatment settings.

The Impact of a Comic Book Intervention on East African-American Adolescents' HPV Vaccine-Related Knowledge, Beliefs and Intentions.

HPV vaccine uptake is low among East African-American (EAA) adolescents. We developed a comic book and evaluated the impact on HPV/HPV-vaccine knowledge, beliefs and vaccine intentions. The intervention was delivered to HPV-unvaccinated EAA adolescents attending educational dinners with their mothers. Adolescents aged 14-17 were sequentially assigned alternately to a pre- or post-test. Results were compared with chi-squared tests and generalized estimating equation models adjusted for age, gender, and mother's language. Among 136 (pre-test = 64, post-test = 72) participants (90% Somali), pre/post differences were observed for proportions of correct responses to questions on HPV (44.0% vs. 82.9%, RR:1.87[95%CI 1.54-2.27]), HPV-vaccine knowledge (42.8% vs. 75.4%, RR:1.74[95%CI 1.46-2.07]), comfort discussing HPV/HPV vaccine with parents (57.8% vs. 90.3% somewhat/very comfortable, RR:1.55[95%CI 1.24-1.94]), and willingness (37.5% vs. 83.3% probably/definitely willing, RR:2.16[95%CI 1.55-3.01]) and intention (34.4% vs. 86.1% somewhat/very likely, RR:2.38[95%CI:1.69-3.37]) to get vaccinated. The intervention improved participants' HPV/HPV-vaccine knowledge, beliefs and vaccine intentions. Similar interventions could be adapted for other racial/ethnic minorities.

Cytomegalovirus Viremia and Clinical Outcomes in Kenyan Children Diagnosed With Human Immunodeficiency Virus (HIV) in Hospital.

BACKGROUND: Cytomegalovirus (CMV) viremia is common in human immunodeficiency virus (HIV) infection and is associated with worse long-term outcomes. To date, no studies have assessed CMV viremia in children diagnosed with HIV in hospital. METHODS: We studied CMV viremia and clinical outcomes in 163 Kenyan children aged 2 months to 12 years, diagnosed with HIV in hospital. CMV DNA levels in plasma were measured using quantitative polymerase chain reaction (PCR). Regression models were used to assess associations between CMV viremia ≥1000 IU/mL and the risk of continued hospitalization or death at 15 days, duration of hospitalization, and 6-month mortality. RESULTS: At enrollment, 62/114 (54%) children had CMV viremia, and 20 (32%) were ≥1000 IU/mL. Eleven CMV reactivations were observed after admission. The prevalence and level of CMV viremia were highest in children <2 years and lowest in children ≥5 years old. CMV viremia ≥1000 IU/mL was independently associated with age <2 years (P = .03), higher log10 HIV RNA level (P = .01), and height-for-age z score >-2 (P = .02). Adjusting for age and log10 HIV RNA, the relative risk of death or continued hospitalization at 15 days was 1.74 (95% confidence interval [CI] = 1.04, 2.90), and the hazard ratio of 6-month mortality was 1.97 (95% CI = .57, 5.07) for children with CMV DNA ≥1000 IU/mL compared to lower-level or undetectable CMV DNA. Children with CMV DNA ≥1000 IU/mL were hospitalized a median ~5 days longer than children with lower-level or undetectable CMV DNA (P = .002). CONCLUSIONS: In this nested observational study, CMV viremia was common in hospitalized children with HIV, and levels ≥1000 IU/mL were associated with increased risk of mortality and longer hospitalization.

The impact of an educational forum intervention on East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children.

OBJECTIVE: HPV vaccine uptake in U.S. East African adolescents is low. We developed and evaluated a culturally-targeted interactive educational intervention for East African immigrant mothers to increase HPV-vaccine-related knowledge, attitudes, and intentions to vaccinate adolescent children. METHODS: Eligible mothers had ≥ 1 11-17-year-old child and reported all children's HPV vaccination status as unvaccinated or unknown. The intervention was delivered via 10 dinners in the Seattle metropolitan area (8 with the Somali community, 2 with the Ethiopian community). Educational presentations and pre/post-tests on knowledge, attitudes, and intentions were conducted in the participants' native language by a co-ethnic physician. Pre/post differences in responses were evaluated with McNemar's tests and GEE models. HPV vaccination uptake 6-months post-intervention was evaluated using state immunization registry data. RESULTS: Of 115 participating mothers, most (84%) were Somali and < 40 years of age (60%). Median years of formal education was 8 (range 0-16), and 61% reported a household income <$25,000. Knowledge of HPV/HPV-vaccines was low pre-intervention, with correct responses ranging from 4% to 39% (61%-91% of responses were "not sure"); correct post-intervention responses ranged from 29% to 97%. Pre-intervention, only 12% of mothers thought they had enough information to make a decision about vaccination, compared to 90% post-intervention. Pre-intervention, only 16% of mothers reported that they were somewhat or very likely to vaccinate their child, compared to 83% post-intervention. All pre/post comparisons were statistically significantly different (p < 0.0001). Although mothers were more likely to report correct HPV-related knowledge and positive vaccine attitudes and intentions post-intervention, only two mothers' children initiated HPV vaccination within 6 months after the intervention. CONCLUSIONS: Results illustrate that a culturally targeted educational intervention effectively increased East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children. Future research should identify additional intervention components that can bridge the gap between intention and behavior to facilitate HPV vaccine uptake.

A Prospective Study of Depressive Symptoms, Condomless Sex, and HIV Viral Load in HIV-Positive Female Sex Workers in Kenya.

The relationships between depressive symptoms, viral suppression, and condomless sex were examined in a prospective cohort study of 369 HIV-positive Kenyan female sex workers. Participants were screened for depressive symptoms at baseline and every six months until completion of the study (up to 66 months). HIV viral load (VL) was measured every six months and prostate specific antigen (PSA) testing in vaginal secretions was performed quarterly. Mild or greater depressive symptoms were found in 100 (27.1%) women and were associated with increased risk of detectable VL (aRR 1.41, 95%CI 0.97-2.07, p-value = 0.07), but were not associated with detectable PSA. The co-occurrence of PSA detection and detectable VL at the same visit suggests the potential for HIV transmission but was uncommon (2.4% of visits). The prevalence of depressive symptoms and the association with detectable VL suggests the need for screening and treatment of depression for comprehensive HIV care in this population.

A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus-Exposed Uninfected Infants.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. METHODS: We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). RESULTS: Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24-1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22-1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. CONCLUSIONS: Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. CLINICAL TRIALS REGISTRATION: NCT02613169.

Psychosocial Factors, Condomless Sex, and Detectable Viral Load in HIV-Positive Women in Serodiscordant Couples in Nairobi, Kenya.

This prospective study of HIV-positive Kenyan women in serodiscordant couples examined relationships between psychosocial factors, viral suppression, and condomless sex. Participants were screened for alcohol use disorders and intimate partner violence (IPV) annually and depressive symptoms every 6 months. Prostate specific antigen (PSA) detection was used as a marker for condomless sex. A total of 151 participants contributed 349 person-years of follow-up. Hazardous/harmful alcohol use was associated with increased risk of detecting PSA in vaginal secretions (aRR 1.99, 95%CI 1.08-3.66, χ2 = 4.85 (1)), while IPV and depression were not. Events representing HIV transmission potential, where there was biological evidence of condomless sex at a visit with a detectable plasma viral load, were observed at 2% of visits. The high prevalence of IPV and association between alcohol use and sexual risk suggest the need for monitoring and support for these conditions as part of comprehensive HIV care for women.

Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children.

INTRODUCTION: HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB disease, it is important to define when and how TB preventive interventions exert their effect in order to develop effective prevention strategies in this high-risk population. METHODS AND ANALYSIS: We designed a non-blinded randomised controlled trial to determine efficacy of isoniazid (INH) to prevent primary Mtb infection among HEU children. Target sample size is 300 (150 infants in each arm). Children are enrolled at 6 weeks of age from maternal and child health clinics in Kenya and are randomised to receive 12 months of daily INH ~10 mg/kg plus pyridoxine or no INH. The primary endpoint is Mtb infection, assessed by interferon-gamma release assay QuantiFERON-TB Gold Plus (QFT-Plus) or tuberculin skin test after 12 months post-enrolment. Secondary outcomes include severe adverse events, expanded Mtb infection definition using additional QFT-Plus supernatant markers and determining correlates of Mtb infection. Exploratory analyses include a combined outcome of TB infection, disease and mortality, and sensitivity analyses excluding infants with baseline TB-specific responses on flow cytometry. ETHICS AND DISSEMINATION: An external and independent Data and Safety Monitoring Board monitors adverse events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy-makers, the local community and participants. TRIAL REGISTRATION NUMBER: NCT02613169; Pre-results.

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines.

OBJECTIVES: Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines. METHODS: In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1ß. RESULTS: Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1ß concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (ß=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1ß (ß=0.96, 95% CI 0.19 to 1.74; p=0.016). CONCLUSIONS: This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.

Male Partner Linkage to Clinic-Based Services for Sexually Transmitted Infections and Human Immunodeficiency Virus Services Following Couple Home-Based Education and Testing.

BACKGROUND: Home-based human immunodeficiency virus (HIV) testing and education has increased HIV test uptake and access to health services among men. We studied how a home-based antenatal intervention influenced male partner utilization of clinic-based HIV and sexually transmitted infection (STI) services, linkage to HIV care and medical circumcision. METHODS: We conducted a secondary analysis within a randomized controlled trial of pregnant women attending antenatal care in Kenya. Women and their male partners received either a home-based couple intervention or an invitation letter for clinic-based couple HIV testing. The home-based intervention included education on STI symptoms, STI and HIV treatment and male circumcision for HIV prevention. Male self-reported outcomes were compared using relative risks at 6 months postpartum. RESULTS: Among 525 women, we reached 487 (93%) of their male partners; 247 men in the intervention arm and 240 men in the control arm. Men who received the intervention were more likely to report an STI consultation (n = 47 vs. 16; relative risk, 1.59; 95% confidence interval, 1.33-1.89). Among 23 men with newly diagnosed HIV, linkage to HIV care was reported by 4 of 15 in the intervention (3 men had missing linkage data) and 3 of 5 men in the control arms (relative risk, 0.66; 95% confidence interval, 0.34-1.29). Although the intervention identified 3 times more men with new HIV infection, the study lacked power to find significant differences in linkage to HIV care. Few eligible men sought medical circumcision (4 of 72 intervention and 2 of 88 control). CONCLUSIONS: Home-based couple education and testing increased STI consultations among male partners of pregnant women, but appeared insufficient to overcome the barriers involved in linkage to HIV care and medical circumcision.

Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial.

Importance: The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. Objective: To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and Participants: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. Interventions: Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and Measures: The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. Results: Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and Relevance: In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial Registration: ClinicalTrials.gov Identifier: NCT01298596.

Performance of family planning clinics in conducting recommended HIV counseling and testing in Mombasa County, Kenya: a cross-sectional study.

BACKGROUND: A high proportion of African women utilize family planning (FP) services. Accordingly, incorporating HIV testing into FP services may strategically target the first WHO 90-90-90 goal of 90% of people living with HIV knowing their status. METHODS: The objective of this analysis was to determine the proportion of new FP clients counseled and tested for HIV, as well as correlates of HIV testing, in a random sample of 58 FP clinics in Mombasa County, Kenya. Structured interviews of FP clinic managers collected data on characteristics of FP clinics and staff. Study staff performed a 3-month review of FP registers, summarizing new client HIV testing and counseling (HTC). Because overall rates of HTC were quite low, a binary variable was created comparing clinics performing any HIV counseling and/or testing to clinics performing none. Generalized linear models were used to calculate prevalence ratios (PR) and identify correlates of HTC. Factors associated with any HTC with a p-value < 0.10 in univariate analysis were included in a multivariate analysis. RESULTS: Of the 58 FP clinics, 26 (45%) performed any counseling for HIV testing, and 23 (40%) performed any HIV testing. Counseling for HIV testing was conducted for 815/4389 (19%) new clients, and HIV testing was performed for 420/4389 (10%). Clinics without trained HIV testing providers uniformly did not conduct HIV counseling and/or testing (0/12 [0%]), while 27/46 (59%) of clinics with ≥1 provider performed some HTC (p < 0.001). In the subset of 46 clinics with ≥1 trained HIV testing provider, correlates of performing HTC included being a public versus non-public clinic (PR 1.70 95%CI 1.01-2.88), and having an HIV comprehensive care center (CCC) onsite (PR 2.05, 95%CI 1.04-4.06). CONCLUSION: Trained HIV testing providers are crucial for FP clinics to perform any HTC. Approaches are needed to increase routine HTC in FP clinics including staffing changes and/or linkages with other testing services (in standalone VCT services or lab facilities) in order to improve the implementation of existing national guidelines. A future cluster randomized trial is planned to test an implementation strategy, the Systems Analysis and Improvement Approach (SAIA) to increase HTC in FP clinics.