Evaluation of syndromic algorithms for managing sexually transmitted infections among pregnant women in Kenya

Session presented on Thursday, July 21, 2016: Purpose: Women with Trichomonas vaginalis (TV), Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) during pregnancy have increased risk for adverse obstetric outcomes. Laboratory testing for these sexually transmitted infections (STIs) is often unavailable in resource-limited settings, and pregnant women are managed using syndromic algorithms developed by the World Health Organization (WHO). These algorithms begin with a patient\u27s report of relevant symptoms which triggers a subsequent clinical assessment of signs to inform recommended treatment that will broadly cover likely STIs. We evaluated the diagnostic validity of WHO syndromic algorithms for TV, GC and CT in a pregnant cohort in Kenya. Methods: We used baseline data from a prospective study of peripartum HIV acquisition that enrolled HIV-uninfected pregnant women at two antenatal care clinics in Western Kenya; women with HIV infection detected at enrollment or during follow-up were excluded. All women were interviewed, underwent pelvic examinations by study clinicians and had vaginal and cervical swabs collected for TV, CT, and GC assessment. Laboratory testing for STI diagnosis included wet mount microscopy for TV and nucleic acid amplification tests (NAAT) for GC and CT. In addition, symptomatic women were treated for TV, CT and GC according to WHO and Kenyan national syndromic management guidelines for women with abnormal vaginal discharge and/or vaginal itching. Laboratory-confirmed diagnosis of TV, CT or GC not covered by syndromic treatment was treated at their subsequent study visit. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of syndromic algorithms were calculated compared to laboratory diagnosis as the gold standard. Results: Of 1279 HIV-uninfected women in the overall cohort, 1275 (99%) had complete TV, CT and GC assessment at baseline, and were included in the present analysis. Women enrolled at a median of 22 weeks gestation (interquartile range [IQR] 18-26), median age was 22 years (IQR 19-27), and most were married (78%) and self-reported no prior STIs (94%). Prevalence of any STI was 13%. TV, GC and CT were detected in 6%, 3% and 5% of women, respectively. Overall, 20% of women with STIs reported abnormal discharge compared to 9% of women without STIs (p\u3c0.001); there was no difference in report of vaginal itching among women with and without STIs (12% vs 18%, p=0.079). Among women with any STI, symptoms were commonly reported in women with TV (31%), and abnormal vaginal discharge was more frequently reported than vaginal itching (28% vs. 13%, p\u3c0.001). Among women with CT and GC, 23% and 9% reported symptoms, respectively, and there was no difference in frequency of reported abnormal vaginal discharge and vaginal itching. On clinical exam, abnormal vaginal discharge was found in 18% of women and was found more frequently among women with STIs compared to women without STIs (35% vs 16%, p\u3c0.001). Using a gold standard of laboratory diagnosis of STI (TV, CT, or GC), syndromic diagnosis of any STI (TV, CT, or GC) per clinical exam had a sensitivity of 39% (95% confidence interval [CI] 32%-47%), specificity of 78% (95% CI: 75%-80%), PPV of 21% (95% CI: 16%-26%) and NPV of 90% (95% CI: 88%-92%). Among women who reported abnormal vaginal discharge, which represents an entry point for syndromic management, syndromic diagnosis had a sensitivity of 28% (95% CI: 19-37%), specificity of 92% (95% CI: 74-99%), PPV of 94% (95% CI: 79.2-99.2%) and NPV of 23% (95% CI 15-32%). Syndromic diagnosis also had low sensitivity for individual STIs: TV (51%, 95% CI: 39%-62%), CT (41%, 95% CI: 30%-54%) and GC (22%, 95% CI: 9%-40%). Specificity for individual STIs was similar to estimates for any STI: TV (78%, 95% CI: 75%-80%), CT, (77%, 95% CI: 74%-79%) and GC (76%, 95% CI: 73%-78%). Among 163 women with any STI, 100 (61%) would have been missed without laboratory diagnosis. Conclusion: Among HIV-uninfected pregnant women, STIs were common and syndromic diagnosis had low sensitivity, resulting in missed opportunities for clinical intervention. Novel STI diagnostics are needed to improve Maternal and infant health

Drop-offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

Introduction: Isoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited. Methods: We evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non-initiation and non-completion were assessed using Poisson regression with generalized linear models. Results: Overall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty-nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high-volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non-initiation. IPT non-initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non-suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non-completion. By 24 months after IPT screening, TB incidence was four-fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56). Conclusions: Despite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop-offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6-month course to reduce TB in CLHIV

Evaluation of mHealth strategies to optimize adherence and efficacy of Option B+ prevention of mother-to-child HIV transmission: Rationale, design and methods of a 3-armed randomized controlled trial

Background Lifelong antiretroviral therapy (ART) (Option B+) is recommended for all HIV-infected pregnant/postpartum women, but high adherence is required to maximize HIV prevention potential and maintain maternal health. Mobile health (mHealth) interventions may provide treatment adherence support for women during, and beyond, the pregnancy and postpartum periods. Methods and design We are conducting an unblinded, triple-arm randomized clinical trial (Mobile WACh X) of one-way short message service (SMS) vs. two-way SMS vs. control (no SMS) to improve maternal ART adherence and retention in care by 2 years postpartum. We will enroll 825 women from Nairobi and Western Kenya. Women in the intervention arms receive weekly, semi-automated motivational and educational SMS and visit reminders via an interactive, human-computer hybrid communication system. Participants in the two-way SMS arm are also asked to respond to a question related to the message. SMS are based in behavioral theory, are tailored to participant characteristics through SMS tracks, and are timed along the pregnancy/postpartum continuum. After enrollment, follow-up visits are scheduled at 6 weeks; 6, 12, 18, and 24 months postpartum. The primary outcomes, virological failure (HIV viral load ≥ 1000 copies/mL), maternal retention in care, and infant HIV infection or death, will be compared in an intent to treat analysis. We will also measure ART adherence and drug resistance. Discussion Personalized and tailored SMS to support HIV-infected women during and after pregnancy may be an effective strategy to motivate women to adhere to ART and remain in care and improve maternal and infant outcomes

Herpes Simplex Virus Type 2, Genital Ulcers and HIV-1 Disease Progression in Postpartum Women

Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2

El debido proceso, requisito sine qua non de validez y procedencia para la expropiación del Country Club

A breakdown of the results and findings identified in the sui generis case is essential to emphasize that the contribution of the scientific novelty through its implementation was achieved to discern an assessment of the legality of the expropriation, based on the due process (scientific novelty), background guide a ruling (judgment) in order to establish the primacy of the general interest over the particulas one. It is essential that the due process helps the substantive law to be fully and optimally developed. Therefore, its inhe- rent application allowed to glimpse both ordinary jurisdiction as the administrative jurisdiction to assume the conflict under investigation (expropriation of Country Club), and the constant mistakes arising in the process of law in the execution of expropriation (raised by the parties in the lawsuit), which would be reclaimed through comprehensive reconstruction of procedural scaffolding, above revoking towards absolute ignorance of the general interest thereon instances occured in the disputeAl desglosar los resultados y conclusiones descollantes en el caso sui generis, es primordial hacer hincapié en la contribución de la novedad científica estriba en que en su aplicación, se logró discernir que una evaluación de la legalidad del acto de expropiación, con base en el debido proceso, orientará un pronunciamiento de fondo (sentencia), en aras de constituir la primacía del interés general sobre el particular. Al unísono es esencial aludir que el debido proceso pemite que el derecho sustantivo se desarrolle óptima e íntegramente. Por lo tanto, su aplicación intrínsecamente permitió vislumbrar que sí es posible adelantar paralelamente el proceso de expropiación por vía judicial, para que se conozca en la jurisdicción ordinaria y asimismo en la contencioso administrativa, siendo la primera competente para adelantar la expropiación en stricto sensu, y la segunda, en única instancia, para examinar la legalidad del acto administra- tivo que ordena adelantarl

debido proceso, requisito sine qua non de validez y procedencia para la expropiación del Country Club

Al desglosar los resultados y conclusiones descollantes en el caso sui generis, es primordial hacer hincapié en la contribución de la novedad científica estriba en que en su aplicación, se logró discernir que una evaluación de la legalidad del acto de expropiación, con base en el debido proceso, orientará un pronunciamiento de fondo (sentencia), en aras de constituir la primacía del interés general sobre el particular. Al unísono es esencial aludir que el debido proceso pemite que el derecho sustantivo se desarrolle óptima e íntegramente. Por lo tanto, su aplicación intrínsecamente permitió vislumbrar que sí es posible adelantar paralelamente el proceso de expropiación por vía judicial, para que se conozca en la jurisdicción ordinaria y asimismo en la contencioso administrativa, siendo la primera competente para adelantar la expropiación en stricto sensu, y la segunda, en única instancia, para examinar la legalidad del acto administra- tivo que ordena adelantarla</jats:p

1344. Interferon Gamma Release Assay (IGRA) Responses in HIV-Infected and -Uninfected Women in Pregnancy

Abstract Background Pregnancy and HIV-associated immunologic changes may affect latent TB infection (LTBI) interferon-gamma release assay (IGRA) QuantiFERON TB Gold Plus (QFT-Plus) diagnostic performance. Methods In this ongoing study, HIV-infected and -uninfected women 20–34 weeks gestation without TB in the past year are enrolled from antenatal clinics in western Kenya and tested with QFT-Plus. Mean quantitative IFN- γ responses to mitogen, and M. tuberculosis antigens (TB1 [primarily CD4+] and TB2 [addition of CD8+ response]) were compared using two-sample t-tests. Proportions for categorical variables were compared using univariate logistic regression. Results Among 306 women (HIV+ 127 [41.5%], HIV− 179 [58.5%]) enrolled between January 2018 and March 2019, median maternal and gestational age were 25 years (IQR 21–28) and 28 weeks (IQR 24–32), respectively. Among HIV-infected women at enrollment, 99.2% were on ART, median CD4 count was 440 cells/mm3 (IQR 235–703), 37.5% were virally suppressed, and 60.6% reported having received isoniazid preventive therapy (IPT). Overall, 95 (31.1%) women were QFT-Plus positive (HIV+ 38 [29.9%], HIV− 57 [31.8%], OR 0.90, 95% CI 0.54–1.48, P = 0.671); 190 (62.1%) were negative (HIV+ 81 [63.8%], HIV− 109 [60.9%]), and 21 had indeterminate results (HIV+ 8 [6.3%], HIV− 13 [7.3%], OR 0.83, 95% CI 0.33–2.09, P = 0.690). Mean response to mitogen was similar between HIV-infected and -uninfected women (6.0 vs. 6.1 IU/mL, P = 0.663]. Among QFT-Plus positive women, HIV+ women had significantly lower TB1 responses than HIV− women (HIV+ 2.7 vs. 4.2 IU/mL, P = 0.035). Mean TB2 responses had a similar pattern, but did not reach statistical significance (HIV+ 3.1 vs. 4.3 IU/mL, P = 0.107). Both TB1 and TB2 were positive for 82 women (86.3%), 4 women were only TB1 positive (4.2%), and 8 women were only TB2 positive (8.4%). Conclusion Among pregnant women, HIV-infection was not associated with increased prevalence of QFT+ responses. However, among QFT-positive women, TB1 responses were lower in HIV-positive women with a similar trend observed for TB2 responses. These findings suggest that HIV-associated immunologic changes may influence QFT test performance. Disclosures All authors: No reported disclosures. </jats:sec

An Interactive Text Messaging Intervention to Improve Adherence to Option B+ Prevention of Mother-to-Child HIV Transmission in Kenya: Cost Analysis (Preprint)

BACKGROUND Mobile health (mHealth) approaches offer potentially affordable ways to support the care of HIV-infected patients in overstretched health care systems. However, only few studies have analyzed the costs associated with mHealth solutions for HIV care. OBJECTIVE The aim of this study was to estimate the total incremental costs and incremental cost per beneficiary of an interactive SMS text messaging support intervention within a clinical trial. METHODS The Mobile WAChX trial (NCT02400671) evaluates an interactive semiautomated SMS text messaging intervention to improve adherence to antiretroviral therapy and retention in care among peripartum women infected with HIV in Kenya to reduce the mother-to-child transmission of HIV. Women were randomized to receive one-way versus two-way SMS text messages. Messages were sent weekly, and these messages included motivational and educational content and visit reminders; two-way messaging enabled prompt consultation with the nurse as needed. Microcosting methods were used to collect resource-use data related to implementing the Mobile WAChX SMS text messaging intervention. At 2 sites (Nairobi and Western Kenya), we conducted semistructured interviews with health personnel to identify startup and recurrent activities by obtaining information on the personnel, supplies, and equipment. Data on expenditures and prices from project expense reports, administrative records, and published government salary data were included to estimate the total incremental costs. Using a public provider perspective, we estimated incremental unit costs per beneficiary and per contact during 2017. RESULTS The weighted average annual incremental costs for the two-way SMS text messaging group were US $3725 per facility, US$62 per beneficiary, and US $0.85 per contact to reach 115 beneficiaries. For the one-way SMS text messaging group, the weighted average annual incremental costs were US$2542 per facility, US $41 per beneficiary, and US$0.66 per contact to reach 117 beneficiaries. The largest cost shares were for the personnel: 48.2% (US $1794/US$3725) in two-way and 32.4% (US $825/US$2542) in one-way SMS text messaging groups. Costs associated with software development and communication accounted for 29.9% (US $1872/US$6267) of the costs in both intervention arms (US $1042 vs US$830, respectively). CONCLUSIONS Cost information for budgeting and financial planning is relevant for implementing mHealth interventions in national health plans. Given the proportion of costs related to systems development, it is likely that costs per beneficiary will decline with the scale-up of the interventions. </sec

An Interactive Text Messaging Intervention to Improve Adherence to Option B+ Prevention of Mother-to-Child HIV Transmission in Kenya: Cost Analysis

Background Mobile health (mHealth) approaches offer potentially affordable ways to support the care of HIV-infected patients in overstretched health care systems. However, only few studies have analyzed the costs associated with mHealth solutions for HIV care. Objective The aim of this study was to estimate the total incremental costs and incremental cost per beneficiary of an interactive SMS text messaging support intervention within a clinical trial. Methods The Mobile WAChX trial (NCT02400671) evaluates an interactive semiautomated SMS text messaging intervention to improve adherence to antiretroviral therapy and retention in care among peripartum women infected with HIV in Kenya to reduce the mother-to-child transmission of HIV. Women were randomized to receive one-way versus two-way SMS text messages. Messages were sent weekly, and these messages included motivational and educational content and visit reminders; two-way messaging enabled prompt consultation with the nurse as needed. Microcosting methods were used to collect resource-use data related to implementing the Mobile WAChX SMS text messaging intervention. At 2 sites (Nairobi and Western Kenya), we conducted semistructured interviews with health personnel to identify startup and recurrent activities by obtaining information on the personnel, supplies, and equipment. Data on expenditures and prices from project expense reports, administrative records, and published government salary data were included to estimate the total incremental costs. Using a public provider perspective, we estimated incremental unit costs per beneficiary and per contact during 2017. Results The weighted average annual incremental costs for the two-way SMS text messaging group were US $3725 per facility, US$62 per beneficiary, and US $0.85 per contact to reach 115 beneficiaries. For the one-way SMS text messaging group, the weighted average annual incremental costs were US$2542 per facility, US $41 per beneficiary, and US$0.66 per contact to reach 117 beneficiaries. The largest cost shares were for the personnel: 48.2% (US $1794/US$3725) in two-way and 32.4% (US $825/US$2542) in one-way SMS text messaging groups. Costs associated with software development and communication accounted for 29.9% (US $1872/US$6267) of the costs in both intervention arms (US $1042 vs US$830, respectively). Conclusions Cost information for budgeting and financial planning is relevant for implementing mHealth interventions in national health plans. Given the proportion of costs related to systems development, it is likely that costs per beneficiary will decline with the scale-up of the interventions. </jats:sec