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Background: In Kenya, standard early infant diagnosis (EID) with polymerase chain reaction (PCR) testing at 6-week postnatal achieves early treatment initiation (

Male involvement in prevention of mother to child transmission of HIV (PMTCT) care is associated with improved maternal and child outcomes. We conducted a mixed-methods study at two Kenyan government hospitals. We quantitatively assessed women’s expectations and preferences for male partner involvement in PMTCT and male partner attendance at PMTCT appointments. Qualitative interviews with women during the postpartum period assessed types of support women received from their male partners. At enrollment, most participants wanted (75%) and expected (69%) male partners to attend appointments; yet, only 9% had a male partner attend any appointments. Most women agreed that their partner would: support them financially (81%), help follow doctor’s guidance (61%), support a hospital-based delivery (85%), and want to receive text messages (68%). Expectations and preferences varied by women’s characteristics, most notably experiences with mistreatment, disclosure status, and knowledge of male partner’s HIV status. In qualitative interviews, instrumental (financial) support was the most frequently discussed type of support. Male partners also provided informational support by reminding women of medication or appointments. Women reported a variety of ways in which their male partners supported them through PMTCT; however, there was a gap between women’s expectation for male partner attendance and the level of male attendance achieved.

BackgroundPrevention of mother-to-child HIV transmission (PMTCT) services in Kenya can be strengthened through the delivery of relevant and culturally appropriate SMS messages.MethodsThis study reports on the results of focus groups conducted with pre and postnatal women living with HIV (5 groups,n = 40) and their male partners (3 groups,n = 33) to elicit feedback and develop messages to support HIV+ women’s adherence to ART medication, ANC appointments and a facility-based birth. The principles of message design informed message development.ResultsRespondents wanted ART adherence messages that were low in verbal immediacy (ambiguous), came from an anonymous source, and were customized in timing and frequency. Unlike other studies, low message immediacy was prioritized over customization of message content. For retention, participants preferred messages with high verbal immediacy—direct appointment reminders and references to the baby—sent infrequently from a clinical source.ConclusionOverall, participants favored content that was brief, cheerful, and emotionally appealing.

We identified mortality predictors among HIV-exposed uninfected infants and infants living with HIV in Kenyan early infant diagnosis services between 2012 and 2017. Younger maternal age and absence of antenatal antiretroviral therapy among HIV-exposed uninfected infants (n = 2366) and travel time to hospital and delayed infant testing among infants living with HIV (n = 130) predicted mortality, highlighting the importance of supporting engagement in maternal/pediatric HIV services.

Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39–65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother–infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.

The HIV Infant Tracking System (HITSystem) is an eHealth intervention to improve early infant diagnosis (EID) through alerts to providers and text messages to mothers. This study explored mothers' experiences receiving standard and HITSystem-enhanced EID services to assess perceived intervention benefits, acceptability, and opportunities for improvement. This qualitative study was embedded within a cluster-randomized control trial to evaluate the HITSystem at six Kenyan government hospitals (3 intervention, 3 control). We conducted semi-structured interviews with 137 mothers attending EID follow-up visits. Compared to control sites, participants at HITSystem sites described enhanced EID quality; HITSystem-generated texts informed them of result availability and retesting needs, provided cues-to-action for clinic attendance, and engendered opportunities for patient support. They described improved EID efficiency through shorter waiting periods for results and fewer hospital visits. Participants reported high satisfaction with EID and acceptability of text messages; however, modifications to ensure text delivery, increase repeat testing reminders, include low literacy content options, and provide encouraging messages were suggested. These user experience data suggest improvements in EID at HITSystem sites when compared with control sites.

The HIV Infant Tracking System (HITSystem) is a web-based intervention linking providers of early infant diagnosis, laboratory technicians, and mothers and infants to improve outcomes for HIV-exposed infants. We aimed to evaluate the efficacy of the HITSystem on key outcomes of early infant diagnosis.We did a cluster-randomised trial at six hospitals in Kenya, which were matched on geographic region, resource level, and volume of patients (high, medium, and low). We randomly allocated hospitals within a matched pair to either the HITSystem (intervention; n=3) or standard of care (control; n=3). A random number generator was used to assign clusters. Investigators were unaware of the randomisation process. Eligible participants were mothers aged 18 years or older with an infant younger than 24 weeks presenting for their first early infant diagnosis appointment. The primary outcome was complete early infant diagnosis retention, which was defined as receipt of all indicated age-specific interventions until 18 months post partum (for HIV-negative infants) or antiretroviral therapy initiation (for HIV-positive infants). Analysis was per protocol in all randomised pairs judged eligible, excluding infant deaths and those who moved or were transferred to another health facility. Modified intention-to-treat sensitivity analyses judged all infant deaths and transfers as incomplete early infant diagnosis retention. Separate multivariable logistic regression analyses were done with intervention group, hospital volume, and significant covariates as fixed effects. This trial is registered with ClinicalTrials.gov, number NCT02072603; the trial has been completed.Between Feb 16, 2014, and Dec 31, 2015, 895 mother-infant pairs were enrolled. Of these, 87 were judged ineligible for analysis, 26 infants died, and 92 pairs moved or were transferred to another health facility. Thus, data from 690 mother-infant pairs were analysed, of whom 392 were allocated to the HITSystem and 298 to standard of care. Mother-infant pairs were followed up to Sept 30, 2017. Infants diagnosed as HIV-positive were followed up for a median of 2·1 months (IQR 1·6-4·8) and HIV-negative infants were followed up for a median of 17·0 months (IQR 16·6-17·6). Infants enrolled in the HITSystem were significantly more likely to receive complete early infant diagnosis services compared with those assigned standard of care (334 of 392 [85%] vs 180 of 298 [60%]; adjusted odds ratio [OR] 3·7, 95% CI 2·5-5·5; p0·0001). No intervention effect was recorded at high-volume hospitals, but strong effects were seen at medium-volume and low-volume hospitals. Modified intention-to-treat analyses for complete early infant diagnosis were also significant (334 of 474 [70%] vs 180 of 334 [54%]; adjusted OR 2·0, 95% CI 1·4-2·7; p0·0001). No adverse events related to study participation were reported.The HITSystem intervention is effective and feasible to implement in low-resource settings. The HITSystem algorithms have been modified to include HIV testing at birth, and an adapted HITSystem 2.0 version is supporting HIV-positive pregnant women to prevent perinatal transmission and optimise maternal and infant outcomes.National Institute of Child Health and Human Development.

We assessed the preliminary impact of the adapted HIV Infant Tracking System (HITSystem v2.0) intervention on prevention of mother-to-child transmission (PMTCT) outcomes using a matched cluster randomized design in two Kenyan government hospitals. Between November 2017 and June 2019, n = 157 pregnant women with HIV were enrolled and followed from their first PMTCT appointment until 12-weeks postpartum. Data from 135 women were analyzed (HITSystem 2.0: n = 53, standard of care (SOC): n = 82), excluding eight deaths, eight pregnancy losses, and six transfers/moves. The primary outcome, complete PMTCT retention, is an aggregate measure of attendance at all scheduled antenatal appointments, hospital-based delivery, and infant HIV-testing before 7-weeks postnatal. HITSystem 2.0 participants were more likely to receive complete PMTCT services compared to SOC (56.6% vs. 17.1% p

We sought to understand the sequence of testing and treatment among nine infants offered both conventional and point-of-care testing and diagnosed as HIV-positive by 6 months of age in Kenya. One infant received per protocol testing and treatment. Patient-level (late presentation and disengagement), provider-level (reluctance and error/oversight) and system-level (stock outs, errors) challenges delayed diagnosis and treatment. Early point-of-care testing can streamline testing; however, challenges mitigate benefits.

BackgroundTesting infants at birth and with more efficient point of care (POC) HIV diagnostic can streamline EID and expedite infant ART initiation. We evaluated the implementation of at birth and 6-week POC testing to assess the effectiveness and feasibility when implemented by existing hospital staff in Kenya.MethodsFour government hospitals were randomly assigned to receive a GeneXpert HIV-1 Qual (n = 2) or Alere m-PIMA (n = 2) machine for POC testing. All HIV-exposed infants enrolled were eligible to receive POC testing at birth and 6-weeks of age. The primary outcome was repeat POC testing, defined as testing both at birth and 6-weeks of age. Secondary outcomes included predictors of repeat POC testing, POC efficiency (turnaround times of key services), and operations (failed POC results, missed opportunities).ResultsOf 626 enrolled infants, 309 (49.4%) received repeat POC testing, 115 (18.4%) were lost to follow up after an at-birth test, 120 (19.2%) received POC testing at 6-weeks only, 80 (12.8%) received no POC testing, and 2 (0.3%) received delayed POC testing (>12 weeks of age). Three (0.4%) were identified as HIV-positive. Of the total 853 POC tests run at birth (n = 424) or 6-weeks (n = 429), 806 (94.5%) had a valid result documented and 792 (98.3%) results had documented maternal notification. Mean time from sample collection to notification was 1.08 days, with 751 (94.8%) notifications on the same day as sample collection. Machine error rates at birth and 6-weeks were 8.5% and 2.5%, respectively. A total of 198 infants presented for care (48 at birth; 150 at 6-weeks) without receiving a POC test, representing missed opportunities for testing.DiscussionAt birth POC testing can streamline infant HIV diagnosis, expedite ART initiation and can be implemented by existing hospital staff. However, maternal disengagement and missed opportunities for testing must be addressed to realize the full benefits of at birth POC testing.

Kenya introduced universal antiretroviral treatment (ART) for pregnant and breastfeeding women living with HIV (Option B+) in 2014. A retrospective study was conducted to review consecutive records for HIV positive pregnant women presenting for antenatal care (ANC) at five clinics in western Kenya. Known positive women (KP :HIV diagnosis prior to current pregnancy) were compared to newly positive (NP) women regarding virologic suppression and retention in care. Among 165 women included, 71 (43%) NP and 94 (57%) KP, NP were younger (24.5 years (SD 4.6) vs. 28.1 years (SD 5.6) compared to KP (p .001). Almost all NP (97%) were initiated on Option B+ while over half of KP (59%) started ART for clinical/immunological criteria (p .0001). KPs were more likely than NPs to have a VL performed following Kenyan guidelines (64% vs. 31%; p .001). Among those tested, virologic suppression was high in both groups (92% KP vs. 100% NP; p = .31). More KPs (82%) vs. NPs (66%) remained active in care at 15-18 months of follow-up (p = .02). Women newly diagnosed with HIV during pregnancy show poorer uptake of VL testing and worse retention in care than those diagnosed prior to pregnancy.

Background Prevention of mother to child transmission of HIV (PMTCT) services are critical to achieve national and global targets of 90% antiretroviral therapy (ART) coverage in PMTCT, and mother to child transmission rates less than 5%. In 2012, Kenya adopted WHO’s recommended ART regimen for PMTCT “Option B+”. Aims This study assesses progress made in adopting these new guidelines and associated outcomes. Methods We analysed programmatic data of 2604 mother–infant pairs enrolled in the HIV Infant Tracking System (HITSystem) at four government hospitals in Kenya between January, 2013 and December, 2016. We then compared PMTCT trends between 2010 and 2012 and 2013–2016 for the same four government hospitals. Results A total of 2,371 (91.1%) received some ART regimen, however; only 911 (56.2%) mothers received ART regimens compliant with WHO Option B+. From 2013 to 2016, the percent of mothers on WHO Option B + doubled from 42 to 84% (p

Background: Despite progress to expand access to HIV testing and treatment during pregnancy in Kenya, gaps still remain in prevention of mother-to-child transmission of HIV (PMTCT) services. This study addresses the need for effective and scalable interventions to support women throughout the continuum of care for PMTCT services in low-resource settings. Our research team has successfully implemented the HIV Infant Tracking System (HITSystem), a Web-based, system-level intervention to improve early infant diagnosis (EID) outcomes. Objective: This study will expand the scope of the HITSystem to address PMTCT services to bridge the gap between maternal and pediatric HIV services and improve outcomes. This paper describes the intervention development protocol to adapt and pilot an HITSystem version 2.0 to assess acceptability, feasibility, and preliminary PMTCT outcomes in Kenya. Methods: This is a 3-year intervention development study to adapt the current HITSystem intervention to support a range of PMTCT outcomes including appointment attendance, antiretroviral therapy (ART) adherence, hospital deliveries, and integration of maternal and pediatric HIV services in low-resource settings. The study will be conducted in 3 phases. Phase 1 will elicit feedback from intervention users (patients and providers) to guide development and refinement of the new PMTCT components and inform optimal implementation. In Phase 2, we will design and develop the HITSystem 2.0 features to support key PMTCT outcomes guided by clinical content experts and findings from Phase 1. Phase 3 will assess complete PMTCT retention (before, during, and after delivery) using a matched randomized pilot study design in 2 hospitals over 18 months. A total of N=108 HIV-positive pregnant women (n=54 per site) will be enrolled and followed from their first PMTCT appointment until infant HIV DNA Polymerase Chain Reaction testing at the target age of 6 weeks (

Background Infant HIV diagnosis by HIV DNA polymerase chain reaction (PCR) testing at the standard 6 weeks of age is often late to mitigate the mortality peak that occurs in HIV positive infants’ first 2–3 months of life. Kenya recently revised their early infant diagnosis (EID) guidelines to include HIV DNA PCR testing at birth (pilot only), 6 weeks, 6 months, and 12 months postnatal and a final 18-month antibody test. The World Health Organization (WHO) approved point-of-care (POC) diagnostic platforms for infant HIV testing in resource-limited countries that could simplify logistics and expedite infant diagnosis. Sustainable scale-up and optimal utility in Kenya and other high-prevalence countries depend on robust implementation studies in diverse clinical settings. Methods We will pilot the implementation of birth testing by HIV DNA PCR, as well as two POC testing systems (Xpert HIV-1 Qual [Xpert] and Alere q HIV-1/2 Detect [Alere q]), on specimens collected from Kenyan infants at birth (0 to 2 weeks) and 6 weeks (4 to

Delays in traditional HIV DNA PCR testing for early infant diagnosis (EID) at 6 weeks of age result in late antiretroviral treatment (ART). Birth point of care (POC) testing is an emerging strategy with the potential to streamline EID services. We elicited providers' recommendations for introducing birth POC testing to guide strategies in Kenya and similar settings. We conducted formative interviews with 26 EID providers from four Kenyan hospitals prior to POC implementation. Providers discussed the need for comprehensive training, covering both EID and POC-specific topics for all key personnel. Providers highlighted equipment considerations, such as protocols for maintenance and safe storage. Providers emphasized the need for maternal counseling to ensure patient acceptance and most agreed that specimen collection for birth POC testing should occur in the maternity department and supported a multidisciplinary approach. Though most providers supported ART initiation based on a positive birth POC result, a few expressed concerns with result validity. To maximize implementation success, provider training, equipment security, maternal counseling, and logistics of testing must be planned and communicated to providers.

Background The incidence of cervical cancer in Kenya is among the highest in the world. Few Kenyan women are able to access screening, thus fueling the high cervical cancer burden. Self-collected human papilloma Virus (HPV) tests, administered during community-health campaigns in rural areas may be a way to expand access to screening. Methods In December 2015, we carried out a four-day community health campaign (CHC) to educate participants about cervical cancer prevention and offer self-administered HPV screening. Community enumeration, outreach and mobilization preceded the CHC. Samples were sent to Migori County Hospital for HPV DNA testing using careHPV Test Kits. Women were notified of results through their choice of short message service (SMS), phone call, home visit or clinic visit. HPV positive women were referred for cryotherapy following a screen-and-treat strategy. Results Door-to-door enumeration identified approximately 870 eligible women in Ngodhe Community in Migori County. Among the 267 women attending the campaign, 255 women enrolled and collected samples: 243 tests were successfully resulted and 12 were indeterminate. Of the 243 resulted tests, 47 (19%) were positive for HPV, with young age being the only significant predictor of positivity. In multivariate analysis, each additional year of age conferred about a 4% decrease in the odds of testing positive (95% CI 0.1 to 7%, p = 0.046). Just over three-quarters of all women (195/255), were notified of their results. Those who were unable to be reached were more likely to prefer receiving results from clinic (54/60, 90%) and were less likely to have mobile phones (24/60, 73%). Although 76% of HPV positive women were notified of their results, just half (51%) of those testing positive presented for treatment. HPV positive women who successfully accessed the treatment facility did not differ from their non-presenting counterparts by demographics, health history, desired route of notification or access to a mobile phone. Conclusion Nearly a third of eligible women in Ngodhe Community attended the CHC and were screened for cervical cancer. Nearly all women who attended the CHC underwent cervical cancer screening by self-collected HPV tests. Three-quarters of all participants received results, but just half of HPV positive participants presented for treatment in a timely fashion, suggesting that linkage to treatment remains a major challenge. Trial registration NCT02124252, Registered 25 April 2014.

Visual inspection with acetic acid (VIA) is becoming a more widely recommended and implemented screening tool for cervical cancer prevention programs in low-resource settings. Many of these settings have a high prevalence of HIV-infected women. We carried out a cross-sectional validation study to define the sensitivity, specificity and predictive values of VIA among HIV-infected women. Women enrolled in HIV care at the Family AIDS Care and Education Services clinic in Kisumu, Kenya, were recruited for participation. All participants underwent VIA followed by colposcopy performed by a second blinded clinician. At colposcopy, lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Disease status was determined by final histopathologic diagnosis in women who underwent biopsies. A satisfactory colposcopy with no lesions was considered a negative result. From October 2010 to June 2012, 1,432 women underwent VIA and colposcopy. A total of 514 (35.7%) women had a positive VIA, and 179 (12.2%) had CIN2+ confirmed by colposcopically directed biopsy. Sensitivity, specificity, positive and negative predictive values of VIA for CIN2+ were 86.6, 71.6, 30.3 and 97.4%, respectively. Specificity, but not sensitivity, increased with older age. Among older women, sensitivity was affected by CD4+ count and use of antiretroviral therapy. Although they are impacted by age and immune status, test characteristics for VIA among HIV-infected women are similar to what has been reported for general populations. Recommendations to use VIA as a screening tool should not vary by HIV status.

HIV and cervical cancer are intersecting epidemics in many low-resource settings, yet there are few accurate estimates of the scope of this public health challenge. To understand disease prevalence and risk factors for cervical intraepithelial neoplasia 2 or greater (CIN2+), we conducted a cross-sectional study of women undergoing cervical cancer screening as part of routine HIV care in Kisumu, Kenya. Women were offered screening with visual inspection with acetic acid, followed by confirmation with colposcopy and biopsy as needed. Univariable and multivariable analyses were carried out to determine clinical and demographic predictors of prevalent CIN2+. Among 3,241 women screened, 287 (9%) had an initial diagnosis of biopsy-confirmed CIN2+. On multivariable analysis, combined oral contraceptives remained significantly associated with detection of CIN2+ among women on HAART (AOR 1.84, CI 1.20–2.82), and not on HAART (AOR 1.72, 95% CI 1.08–2.73), while use of a progesterone implant was associated with increased detection of CIN2+ (AOR 9.43, 95% CI 2.85–31.20) only among women not on HAART. CD4+ nadir over 500 cells/mm3 was associated with reduced detection of CIN2+ (AOR 0.61, CI 0.38, 0.97) in the overall group, but current CD4+ was only associated with reduced detection of CIN2+ among women not on HAART (AOR 0.42, CI 0.22, 0.80). In conclusion, a history of less severe immunosuppression appeared to reduce the risk of CIN2+ detection, but current CD4+ count was significant only in non-HAART users. The association of CIN2+ with hormonal contraception should be explored more in prospective studies designed to better control for confounding factors.

Objective A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16INK4a has been explored as a biomarker for screening in general populations. Design A 2-year cross-sectional study. Setting 2 large HIV primary care clinics in western Kenya. Participants 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012. Interventions Participants underwent p16INK4a specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis. Primary and secondary outcome measures We measured the sensitivity, specificity and predictive values of p16INK4a ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations. Results Average p16INK4a concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16INK4a to detect biopsy-proven CIN2+. At a p16INK4a cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16INK4a positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16INK4a prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16INK4a prediction. Conclusions p16INK4a ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low specificity. Our study contributes to the ongoing search for a more specific alternative to HPV testing for CIN2+ detection.

Background Women living in Africa experience the highest burden of cervical cancer. Research and investment to improve vaccination, screening, and treatment efforts are critically needed. We systematically reviewed and characterized recent research within a broader public health framework to organize and assess the range of cervical cancer research in Africa. Methods We searched online databases and the Internet for published articles and cervical cancer reports in African countries. Inclusion criteria included publication between 2004 and 2014, cervical cancer-related content pertinent to one of the four public health categories (primary, secondary, tertiary prevention or quality of life), and conducted in or specifically relevant to countries or regions within the African continent. The study design, geographic region/country, focus of research, and key findings were documented for each eligible article and summarized to illustrate the weight and research coverage in each area. Publications with more than one focus (e.g. secondary and tertiary prevention) were categorized by the primary emphasis of the paper. Research specific to HIV-infected women or focused on feasibility issues was delineated within each of the four public health categories. Results A total of 380 research articles/reports were included. The majority (54.6 %) of cervical cancer research in Africa focused on secondary prevention (i.e., screening). The number of publication focusing on primary prevention (23.4 %), particularly HPV vaccination, increased significantly in the past decade. Research regarding the treatment of precancerous lesions and invasive cervical cancer is emerging (17.6 %), but infrastructure and feasibility challenges in many countries have impeded efforts to provide and evaluate treatment. Studies assessing aspects of quality of life among women living with cervical cancer are severely limited (4.1 %). Across all categories, 11.3 % of publications focused on cervical cancer among HIV-infected women, while 17.1 % focused on aspects of feasibility for cervical cancer control efforts. Conclusions Cervical cancer research in African countries has increased steadily over the past decade, but more is needed. Tertiary prevention (i.e. treatment of disease with effective medicine) and quality of life of cervical cancer survivors are two severely under-researched areas. Similarly, there are several countries in Africa with little to no research ever conducted on cervical cancer.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia.

INTRODUCTION HIV-infected women may have higher rates of recurrent cervical precancer after treatment. Knowledge about rates and predictors of recurrence could impact guidelines and program planning, especially in low-resource settings. METHODS In this prospective cohort study in Western Kenya, we followed HIV-infected women at 6 and 12 months after treatment for cervical intraepithelial neoplasia 2 or greater (CIN2+) after treatment with loop electrosurgical excision procedure (LEEP). All women underwent follow-up colposcopy with biopsy as indicated for the diagnosis of CIN2+. We calculated the incidence and predictors of primary disease recurrence after treatment. RESULTS Among the 284 women who underwent LEEP and had at least 1 follow-up visit, there were 37 (13%) cases of CIN2+ detected by 12-month follow-up. Four (10.8%) of the recurrences were invasive cancer, all stage IA1. The 6- and 12-month rates of recurrence were 13.7 and 12.8 cases per 100 person-years of follow-up, respectively. Antiretroviral therapy use did not significantly impact the rate of recurrence (hazard ratio: 1.24, 95% confidence interval: 0.59 to 2.79). The only significant predictor of recurrence in the multivariate analysis was CD4(+) nadir

Visual inspection with Acetic Acid (VIA) and Visual Inspection with Lugol’s Iodine (VILI) are increasingly recommended in various cervical cancer screening protocols in low-resource settings. Although VIA is more widely used, VILI has been advocated as an easier and more specific screening test. VILI has not been well-validated as a stand-alone screening test, compared to VIA or validated for use in HIV-infected women. We carried out a randomized clinical trial to compare the diagnostic accuracy of VIA and VILI among HIV-infected women. Women attending the Family AIDS Care and Education Services (FACES) clinic in western Kenya were enrolled and randomized to undergo either VIA or VILI with colposcopy. Lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Between October 2011 and June 2012, 654 were randomized to undergo VIA or VILI. The test positivity rates were 26.2% for VIA and 30.6% for VILI (p = 0.22). The rate of detection of CIN2+ was 7.7% in the VIA arm and 11.5% in the VILI arm (p = 0.10). There was no significant difference in the diagnostic performance of VIA and VILI for the detection of CIN2+. Sensitivity and specificity were 84.0% and 78.6%, respectively, for VIA and 84.2% and 76.4% for VILI. The positive and negative predictive values were 24.7% and 98.3% for VIA, and 31.7% and 97.4% for VILI. Among women with CD4+ count < 350, VILI had a significantly decreased specificity (66.2%) compared to VIA in the same group (83.9%, p = 0.02) and compared to VILI performed among women with CD4+ count ≥ 350 (79.7%, p = 0.02). VIA and VILI had similar diagnostic accuracy and rates of CIN2+ detection among HIV-infected women. Trial Registration ClinicalTrials.gov NCT02237326

Introduction : HIV and cervical cancer are intersecting epidemics that disproportionately affect one of the most vulnerable populations in the world: women in low- and middle-income countries (LMICs). Historically, the disparity in cervical cancer risk for women in LMICs has been due to the lack of organized screening and prevention programmes. In recent years, this risk has been augmented by the severity of the HIV epidemic in LMICs. HIV-positive women are at increased risk for developing cervical precancer and cancer, and while the introduction of antiretroviral therapy has dramatically improved life expectancies among HIV-positive women it has not been shown to improve cancer-related outcomes. Therefore, an increasing number of HIV-positive women are living in LMICs with limited or no access to cervical cancer screening programmes. In this commentary, we describe the gaps in cervical cancer prevention, the state of evidence for integrating cervical cancer prevention into HIV programmes and future directions for programme implementation and research. Discussion : Despite the biologic, behavioural and demographic overlap between HIV and cervical cancer, cervical cancer prevention has for the most part been left out of sexual and reproductive health (SRH) services for HIV-positive women. Lower cost primary and secondary prevention strategies for cervical cancer are becoming more widely available in LMICs, with increasing evidence for their efficacy and cost-effectiveness. Going forward, cervical cancer prevention must be considered a part of the essential package of SRH services for HIV-positive women. Effective cervical cancer prevention programmes will require a coordinated response from international policymakers and funders, national governments and community leaders. Leveraging the improvements in healthcare infrastructure created by the response to the global HIV epidemic through integration of services may be an effective way to make an impact to prevent cervical cancer among HIV-positive women, but more work remains to determine optimal approaches. Conclusions : Cervical cancer prevention is an essential part of comprehensive HIV care. In order to ensure maximal impact and cost-effectiveness, implementation strategies for screening programmes must be adapted and rigorously evaluated through a framework that includes equal participation with policymakers, programme planners and key stakeholders in the target communities. Keywords: cervical cancer prevention; HIV; integration; low- and middle-income countries. (Published: 1 December 2015) Citation: Huchko MJ et al. Journal of the International AIDS Society 2015, 18(Suppl 5) :20282 http://www.jiasociety.org/index.php/jias/article/view/20282 | http://dx.doi.org/10.7448/IAS.18.6.20282

Abstract 42 Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), and cytology-based programs are not feasible for use in these settings. This has prompted a search for alternative cervical-cancer screening or surveillance methods that can be adopted in LMICs to address the high disease burden. In this study, we seek to evaluate the performance and reliability of cervical p16INK4a biomarker as measured by an ELISA assay among a group of HIV-positive women in a low-resource setting who had normal screening results by gold standard at baseline and at 12-month follow-up. Methods: This prospective study took place at the Family AIDS Care and Education Services (FACES) clinic in Kisumu, Kenya. Participants underwent cervical cancer screening using VIA, colposcopy and collection of cervical HPV p16INK4a samples. Women with negative colposcopies were rescreened at 12-months, and cervical p16INK4a samples were collected. Among women with negative colposcopies at both baseline and follow-up, we investigated the reproducibility of p16INK4a biomarker levels within the same woman between the two visits. Biomarker levels were determined using an ELISA-based biochemical assay. We compared median p16INK4a levels between baseline and follow-up using the paired t-test. We also examined correlation using correlation coefficients and a Bland-Atman plot of differences versus average. A multivariate regression model was fit to identify demographic and clinical variables associated with absolute change in p16INK4a levels. Results: Among the ninety-three women who had normal cervical exams, mean p16INK4a levels increased significantly between baseline and follow-up period, at 20.2 U/ml vs 30.1 U/ml (pConclusion: Our results suggest that there is variability in levels of p16INK4a biomarker as measured by ELISA in HIV-positive women in low-resource settings with normal screening as determined by colposcopy over a 12-month follow-up period. Biomarker levels varied significantly more among older women and those who were HPV positive at baseline, despite normal cervical exams. These data suggest that elevations in p16INK4a biomarker levels may not be a reliable marker of dysplasia in this group of women. Further research in this population as well as replication of these results will be important. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Chemtai Mungo No relationship to disclose Carol Conell No relationship to disclose May Maloba No relationship to disclose Elizabeth Bukusi No relationship to disclose Craig Cohen Consulting or Advisory Role: Symbiomix Inc. Megan Huchko No relationship to disclose

Objective: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. Background: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. Methods: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. Results: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. Conclusion: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.

HIV-infected women are at increased risk for recurrence of cervical dysplasia after treatment. Short-term recurrence rates may reflect treatment efficacy and therefore impact screening protocols and follow-up planning. We conducted a prospective study of 297 HIV-infected women undergoing loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2+ (CIN2+) in an HIV clinic in Kisumu, Kenya. By 6 months after the procedure, 20 (7.1%) of women had recurrent CIN2+. Recurrence was significantly associated with CD4+ nadir but not with highly active antiretroviral therapy use. Longer-term follow-up of this cohort will illustrate the potential impact of highly active antiretroviral therapy and immune status on CIN2/3 disease recurrence.

Objective To determine the prevalence of invasive cervical cancer (ICC) and assess access to, and outcomes of, treatment for ICC among HIV-infected women in Kisumu, Kenya. Methods We performed a retrospective chart review to identify women diagnosed with ICC between October 2007 and June 2012, and to examine the impact of a change in the referral protocol. Prior to June 2009, all women with ICC were referred to a regional hospital. After this date, women with stage IA1 disease were offered treatment with loop electrosurgical excision procedure (LEEP) in-clinic. Results Of 4308 women screened, 58 (1.3%) were diagnosed with ICC. The mean age at diagnosis was 34 years (range, 22–50 years). Fifty-four (93.1%) women had stage IA1 disease, of whom 36 (66.7%) underwent LEEP, 7 (12.9%) had a total abdominal hysterectomy, and 11 (20.4%) had unknown or no treatment. At 6, 12, and 24 months after LEEP, 8.0% (2/25), 25.0% (6/24), and 41.2% (7/17) of women had a recurrence of cervical intraepithelial neoplasia 2 or worse, respectively. Conclusion Most HIV-positive women diagnosed with ICC through screening had early-stage disease. The introduction of LEEP in-clinic increased access to treatment; however, recurrence was high, indicating the need for continued surveillance.

The increasing availability of HIV clinics providing highly active antiretroviral therapy (HAART) has dramatically reduced AIDS-related morbidity and mortality in resource-limited settings. However, the impact of HAART on development and progression of cervical neoplasia and invasive cervical cancer remains uncertain [1]. The longer life expectancy among HIV-infected women receiving HAART may actually increase the overall risk for cervical cancer, underscoring the need for prevention strategies for this high-risk population. A potentially cost-effective way of providing this “primary” care may be through HIV clinics, which are generally well staffed and have more resources than government or private clinics [2]. In addition to utilizing the staffing and infrastructure in place to provide HIV care and HAART, incorporating cervical cancer screening into an HIV clinic visit may increase screening uptake and follow up.