Incorporating the HIV Infant Tracking System into standard-of-care early infant diagnosis of HIV services in Kenya: a cost-effectiveness analysis of the HITSystem randomised trial.

BACKGROUND: The HITSystem efficacy trial showed significant improvements in early infant diagnosis retention, return and notification of infant test results, and earlier antiretroviral therapy (ART) initiation compared with standard-of-care early infant diagnosis services in Kenya. This study aimed to analyse data from the HITSystem trial to assess the cost-effectiveness of the intervention in Kenya. METHODS: In this analysis, we extrapolated results from the HITSystem cluster randomised controlled trial to model early infant diagnosis outcomes and cost-effectiveness if the HITSystem was scaled up nationally in Kenya, compared with standard-of-care outcomes. We used a micro-costing method to collect cost data, which were analysed from a health-system perspective, reflecting the investment required to add HITSystem to existing early infant diagnosis services and infrastructure. The base model used to calculate cost-effectiveness was deterministic and calculated the progression of infants through early infant diagnosis. Differences in progression across study arms were used to establish efficacy outcomes. The number of life-years gained per infant successfully initiating ART were based on the Cost Effectiveness of Preventing AIDS Complications model in east Africa. HITSystem cost data were integrated into the model, and the incremental cost-effectiveness ratio was calculated in terms of cost per life-year gained. Sensitivity analyses were done using the deterministic model with triangular stochastic probability functions for key model parameters added. The number of life-years gained was discounted at 3% and costs were adjusted to 2021 values. FINDINGS: The cost per life-year gained from the HITSystem was US$82·72. Total cost for national HITSystem coverage in Kenya was estimated to be around $2·6 million; covering 82 230 infants exposed to HIV at a cost of $31·38 per infant and a yield of 1133 infants receiving timely ART, which would result in 31 189 life-years gained. With sensitivity analyses, the cost per life-year gained varied from $40·13 to $215·05. 90% of model values across iterations ranged between $55·58 (lower 5% threshold) and $132·38 (upper 95% threshold). INTERPRETATION: The HITSystem would be very cost-effective in Kenya and can optimise the return on the existing investment in the national early infant diagnosis programme. FUNDING: The US National Institute of Child Health and Human Development.

Primary and Triage Cervical Screening Diagnostic Value of Methods for the Detection of Cervical Dysplasia.

Background: Cervical cancer is a leading cause of mortality among women globally. Approaches to reduce cervical cancer incidence and mortality are "screen-and-treat," where positive primary test only is used in the treatment and "screen, triage and treat," where treatment is based on positive primary and triage tests with/without histological analysis. Objectives: To determine cervical screening outcomes among HIV-infected and noninfected women using VIA, Pap smear, and HPV-PCR cervical screening methods and to determine the sensitivity, specificity, PPV and NPV of VIA, Pap smear, and HPV-PCR as primary test and sequential triage based on abnormal histopathology among HIV-infected and noninfected women. Methodology. This was a comparative cross-sectional study where women aged 18-46 years women underwent cervical screening and colposcopy-biopsy test as a positive-confirmatory test in the Referral Hospitals of Eastern Kenya. Results: A total of 317 (HIV negative: 156/317 (49.2%) and HIV positive: 161/317 (50.8%)) women were enrolled. Of these 81/317 (25.6%), 84/317 (26.5%), 96/317 (30.2%), and 78/122 (63.9%) participants had VIA, HPV DNA-PCR, Pap smear, and cervical histology positive results, respectively; average: 27.4% (HIV positive: 21.5%; HIV negative: 5.9%). Majority of women with LSIL [17/317 (5.4%)], HSIL [22/317 (6.9%)], invasive cancer [5/317 (1.6%)], cervicitis [45/317 (14.2%], and candidiasis 47/317 (14.8%) were HIV-infected (p < 0.001). 78/317 (24.6%) participants had positive histology test [ASCUS: 34/317 (10.7%) CIN1:17/317 (5.3%), CIN2: 16/317 (5.0%), CIN3:6/317 (1.9%), and ICC: 5/317 (1.6%)] (p > 0.001). A higher primary diagnostic accuracy was established by HPV DNA-PCR (sensitivity: 95.5%; specificity: 92.6%) than Pap smear and VIA test while in triage testing, high sensitivity was obtained by HPV DNA-PCR parallel testing with VIA test (92.6%) and Pap smear test (92.7%) and VIA cotesting with Pap smear (99.9%). HIV-infected women had increased specificity and reduced sensitivity and diagnostic accuracy by both primary and triage testing approaches. Discussion. Abnormal cervical screening outcome was high among HIV-infected than noninfected women. HIV-infected women had significantly high cases of cervical neoplastic changes. The diagnostic value of primary tests increased upon concurrent testing with other test methods hence reducing the number of women who would have been referred for biopsy. Conclusion: High sensitivity and specificity in detection of CIN+ were established among HIV-infected than HIV noninfected women by HPV DNA-PCR and Pap smear than VIA test. HPV DNA-PCR test and Pap smear are more accurate in primary and sequential triage cervical screening based on abnormal histopathology outcomes among HIV-infected than noninfected women.

Antiretroviral (ARV) Drug Resistance and HIV-1 Subtypes among Injecting Drug Users in the Coastal Region of Kenya.

HIV-1 genetic diversity results into the development of widespread drug-resistant mutations (DRMs) for the first-line retroviral therapy. Nevertheless, few studies have investigated the relationship between DRMs and HIV-1 subtypes among HIV-positive injecting drug users (IDUs). This study therefore determined the association between HIV-1 genotypes and DRMs among the 200 IDUs. Stanford HIV Drug Resistance Database was used to interpret DRMs. The five HIV-1 genotypes circulating among the IDUs were A1 (25 (53.2%)), A2 (2 (4.3%)), B (2 (4.3%)), C (9 (19.1%)), and D (9 (19.1%)). The proportions of DRMs were A1 (12 (52.2%)), A2 (1 (4.3%)), B (0 (0.0%)), C (5 (21.7%)), and D (5 (21.7%)). Due to the large proportion of drug resistance across all HIV-1 subtypes, surveillance and behavioral studies need to be explored as IDUs may be spreading the drug resistance to the general population. In addition, further characterization of DRMs including all the relevant clinical parameters among the larger population of IDUs is critical for effective drug resistance surveillance.

HIV Drug Resistance in Kenyan Infants Diagnosed With HIV and Their Mothers.

The presence and type of HIV drug resistance mutations among 5 infants diagnosed with HIV were assessed and compared with their mothers' viral mutations. Mother and infant blood samples were sequenced and screened for HIV drug resistance mutations using the Stanford HIV Sequence Database. Three of 5 (60%) mother-infant pairs harbored HIV drug resistance mutations.

Human Papillomavirus Types Associated with Cervical Dysplasia among HIV- and Non-HIV-Infected Women Attending Reproductive Health Clinics in Eastern Kenya.

BACKGROUND: Human papillomavirus (HPV) causes over 99% of all cervical cancer globally. In 2019, it was responsible for 3286 deaths in Kenya. Data on the epidemiological distribution of HPV genotypes by cervical dysplasia and HIV-infected women which is important in designing prevention strategy monitoring treatment and management of cervical cancer is lacking in Eastern Kenya. OBJECTIVE: To determine HPV genotype prevalence and their association with cervical dysplasia among HIV-infected (cases) and noninfected (control) women aged 18-48 years seeking reproductive healthcare. METHODS: A cervical broom was softly rotated 360 degrees five times to exfoliate cells from the region of the transformation zone, squamocolumnar junction, and endocervical canal for HPV genotyping. Social-demographic and risk factors responsible for HPV acquisition were collected using a questionnaire. Laboratory outcome and questionnaire data statistical relationships were computed using Pearson chi-square test. RESULTS: 317 women (cases: 161 (50.8%), control 156 (49.2%), mean age: 34.3,SD ± 10.4, range 18-46 years) were recruited from Embu (85/317 (26.8%)), Isiolo (64/317 (20.2%)), Kirinyaga (56/317 (17.7%)), Meru (81/317 (25.6%)), and Tharaka-Nithi (31/317 (9.8%)). The frequency HPV genotypes detected by cervical dysplasia were CIN1 (cases: HPV81 (12/317 (3.8%)), HPV11 (2/317 (0.6%)); control: HPV53 and 66 coinfection (1/317 (0.3%)), CIN2 (cases: HPV11, HPV16, HPV66 ((1/317 (0.3%) each), HPV81 (6/317 (1.9%)), and single case (1/317 (0.3%)) of HPV11 and 66, HPV81 and 44, HPV81 and 88, HPV9 and 53, and HPV16 and 58 coinfection; control: HPV81 (2/317 (0.6%)) and invasive cervical cancer (cases: HPV16 (1/317 (0.3%)) and HPV81 (3/317 (0.9%)); control: HPV16 and 66 (1/317 (0.3%))). CONCLUSIONS: There was a higher frequency of both high-risk and low-risk HPV genotypes associated with cervical dysplasia among HIV-infected than HIV-uninfected women seeking reproductive health care. This study provides epidemiological data on the existence of nonvaccine HPV types associated with cervical dysplasia in the region.

Piloting the Feasibility and Preliminary Impact of Adding Birth HIV Polymerase Chain Reaction Testing to the Early Infant Diagnosis Guidelines in Kenya.

BACKGROUND: In Kenya, standard early infant diagnosis (EID) with polymerase chain reaction (PCR) testing at 6-week postnatal achieves early treatment initiation (<12 weeks) in <20% of HIV+ infants. Kenya's new early infant diagnosis guidelines tentatively proposed adding PCR testing at birth, pending results from pilot studies. METHODS: We piloted birth testing at 4 Kenyan hospitals between November 2017 and November 2018. Eligible HIV-exposed infants were offered both point-of-care and PCR HIV testing at birth (window 0 to <4 weeks) and 6 weeks (window 4-12 weeks). We report the: proportion of infants tested at birth, 6-week, and both birth and 6-week testing; median infant age at results; seropositivity and antiretroviral therapy initiation. RESULTS: Final sample included 624 mother-infant pairs. Mean maternal age was 30.4 years, 73.2% enrolled during antenatal care and 89.9% had hospital deliveries. Among the 590 mother-infants pairs enrolled before 4 weeks postnatal, 452 (76.6%) completed birth testing before 4 weeks, with 360 (79.6%) testing within 2 weeks, and 178 (39.4%) before hospital discharge (0-2 days). Mothers were notified of birth PCR results at a median infant age of 5.4 weeks. Among all 624 enrolled infants, 575 (92.1%) were tested during the 6-week window; 417 (66.8%) received testing at both birth and 6-weeks; and 207 received incomplete testing (93.3% only 1 PCR and 6.7% no PCR). Four infants were diagnosed with HIV, and 3 infants were initiated on antiretroviral therapy early, before 12 weeks of age. CONCLUSIONS: Uptake of PCR testing at birth was high and a majority of infants received repeat testing at 6 weeks of age.

A Review of Current Strategies Towards the Elimination of Latent HIV-1 and Subsequent HIV-1 Cure.

BACKGROUND: During the past 35 years, highly effective ART has saved the lives of millions of people worldwide by suppressing viruses to undetectable levels. However, this does not translate to the absence of viruses in the body as HIV persists in latent reservoirs. Indeed, rebounded HIV has been recently observed in the Mississippi and California infants previously thought to have been cured. Hence, much remains to be learned about HIV latency, and the search for the best strategy to eliminate the reservoir is the direction current research is taking. A systems-level approach that fully recapitulates the dynamics and complexity of HIV-1 latency In vivo and is applicable in human therapy is prudent for HIV eradication to be more feasible. OBJECTIVES: The main barriers preventing the cure of HIV with antiretroviral therapy have been identified, progress has been made in the understanding of the therapeutic targets to which potentially eradicating drugs could be directed, integrative strategies have been proposed, and clinical trials with various alternatives are underway. The aim of this review is to provide an update on the main advances in HIV eradication, with particular emphasis on the obstacles and the different strategies proposed. The core challenges of each strategy are highlighted and the most promising strategy and new research avenues in HIV eradication strategies are proposed. METHODS: A systematic literature search of all English-language articles published between 2015 and 2019, was conducted using MEDLINE (PubMed) and Google scholar. Where available, medical subject headings (MeSH) were used as search terms and included: HIV, HIV latency, HIV reservoir, latency reactivation, and HIV cure. Additional search terms consisted of suppression, persistence, establishment, generation, and formation. A total of 250 articles were found using the above search terms. Out of these, 89 relevant articles related to HIV-1 latency establishment and eradication strategies were collected and reviewed, with no limitation of study design. Additional studies (commonly referenced and/or older and more recent articles of significance) were selected from bibliographies and references listed in the primary resources. RESULTS: In general, when exploring the literature, there are four main strategies heavily researched that provide promising strategies to the elimination of latent HIV: Haematopoietic Stem-Cell Transplantation, Shock and Kill Strategy, Gene-specific transcriptional activation using RNA-guided CRISPR-Cas9 system, and Block and Lock strategy. Most of the studies of these strategies are applicable in vitro, leaving many questions about the extent to which, or if any, these strategies are applicable to complex picture In vivo. However, the success of these strategies at least shows, in part, that HIV-1 can be cured, though some strategies are too invasive and expensive to become a standard of care for all HIV-infected patients. CONCLUSION: Recent advances hold promise for the ultimate cure of HIV infection. A systems-level approach that fully recapitulates the dynamics and complexity of HIV-1 latency In vivo and applicable in human therapy is prudent for HIV eradication to be more feasible. Future studies aimed at achieving a prolonged HIV remission state are more likely to be successful if they focus on a combination strategy, including the block and kill, and stem cell approaches. These strategies propose a functional cure with minimal toxicity for patients. It is believed that the cure of HIV infection will be attained in the short term if a strategy based on purging the reservoirs is complemented with an aggressive HAART strategy.

Programmatic evaluation of feasibility and efficiency of at birth and 6-week, point of care HIV testing in Kenyan infant.

BACKGROUND: Testing 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. METHODS: Four 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). RESULTS: Of 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. DISCUSSION: At 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.

Cervical Dysplasia, Infection, and Phylogeny of Human Papillomavirus in HIV-Infected and HIV-Uninfected Women at a Reproductive Health Clinic in Nairobi, Kenya.

High risk human Papillomavirus (HPV) infections ultimately cause cervical cancer. Human Immunodeficiency Virus (HIV) infected women often present with multiple high-risk HPV infections and are thus at a higher risk of developing cervical cancer. However, information on the circulating high-risk HPV genotypes in Kenya in both HIV-infected and HIV-uninfected women is still scanty. This study is aimed at determining the phylogeny and the HPV genotypes in women with respect to their HIV status and at correlating this with cytology results. This study was carried out among women attending the Reproductive Health Clinic at Kenyatta National Hospital, a referral hospital in Nairobi, Kenya. A cross-sectional study recruited a total of 217 women aged 18 to 50 years. Paired blood and cervical samples were obtained from consenting participants. Blood was used for serological HIV screening while cervical smears were used for cytology followed by HPV DNA extraction, HPV DNA PCR amplification, and phylogenetic analysis. Out of 217 participants, 29 (13.4%) were HIV seropositive, while 68 (31.3%) were positive for HPV DNA. Eight (3.7%) of the participants had abnormal cervical cytology. High-risk HPV 16 was the most prevalent followed by HPV 81, 73, 35, and 52. One participant had cervical cancer, was HIV infected, and had multiple high-risk infections with HPV 26, 35, and 58. HPV 16, 6, and 81 had two variants each. HPV 16 in this study clustered with HPV from Iran and Africa. This study shows the circulation of other HPV 35, 52, 73, 81, 31, 51, 45, 58, and 26 in the Kenyan population that play important roles in cancer etiology but are not included in the HPV vaccine. Data from this study could inform vaccination strategies. Additionally, this data will be useful in future epidemiological studies of HPV in Nairobi as the introduction or development of new variants can be detected.

Predictors of Early ART Initiation Among HIV + Infants in Kenya: A Retrospective Review of HITSystem Data from 2013 to 2017.

OBJECTIVE: Early initiation of antiretroviral therapy (ART, before 12 weeks of age) among infants living with HIV reduces infant mortality and slows disease progression. However, inefficiencies in early infant diagnosis processes prevents timely ART initiation among infants living with HIV in Kenya. This study assesses predictors of early ART initiation among infants living with HIV in Kenya. DESIGN: We retrospectively reviewed data from 96 infants living with HIV born between January 2013 and June 2017 at 6 Kenyan government hospitals. METHODS: The primary outcome was infant receipt of ART by 12 weeks of age. We assessed bivariable and multivariable predictors of ART initiation by 12 weeks of age. RESULTS: Among 96 infants living with HIV, 82 (85.4%) infants initiated ART at a median infant age of 17.1 weeks. Of the 82 infants who started ART, only 17 (20.7%) initiated ART by 12 weeks of age. In multivariable logistic regression analyses, testing per national guidelines (< 7 weeks of age) (aOR 40.14 [3.96-406.97], p = 0.002), shorter turnaround time for result notification (≤ 4 weeks) (aOR 11.30 [2.02-63.34], p = 0.006), and ART initiation within 3 days of mother notification (aOR 7.32 [1.41-38.03], p = 0.006) were significantly associated with ART initiation by 12 weeks of age. CONCLUSION: Current implementation of early infant diagnosis services in Kenyan only achieves targets for early ART initiation in one-fifth of infants with HIV. Strengthening services to support earlier infant testing and streamlined processes for early infant diagnosis may increase the proportion of infants who receive timely ART.

Predictors of Mortality Among HIV-exposed Infants Through 18 Months of Age in Kenya: A Retrospective Review of Programmatic Data.

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.

Rates and Predictors of HIV-Exposed Infants Lost to Follow-Up During Early Infant Diagnosis Services in Kenya.

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.

eHealth Interventions for Early Infant Diagnosis: Mothers' Satisfaction with the HIV Infant Tracking System in Kenya.

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.

Infant HIV testing at birth using point-of-care and conventional HIV DNA PCR: an implementation feasibility pilot study in Kenya.

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 < 24 weeks) postnatal. The formative phase will inform optimal implementation of birth testing and two POC testing technologies. Qualitative interviews with stakeholders (providers, parents of HIV-exposed infants, and community members) will assess attitudes, barriers, and recommendations to optimize implementation at their respective sites. A non-blinded pilot study at four Kenyan hospitals (n = 2 Xpert, n = 2 Alere q platforms) will evaluate infant HIV POC testing compared with standard of care HIV DNA PCR testing in both the birth and 6-week windows. Objectives of the pilot are to assess uptake, efficiency, quality, implementation variables, user experiences of birth testing with both POC testing systems or with HIV DNA PCR, and costs. DISCUSSION: This study will generate data on the clinical impact and feasibility of adding HIV testing at birth utilizing POC and traditional PCR HIV testing strategies in resource-limited settings. Data from this pilot will inform the optimal implementation of Kenya's birth testing guidelines and of POC testing systems for the improvement of EID outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03435887. Registered 26 February 2018.

Evaluation of the HIV Infant Tracking System (HITSystem) to optimise quality and efficiency of early infant diagnosis: a cluster-randomised trial in Kenya.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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; p<0·0001). 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; p<0·0001). No adverse events related to study participation were reported. INTERPRETATION: 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. FUNDING: National Institute of Child Health and Human Development.

Implementing eHealth Technology to Address Gaps in Early Infant Diagnosis Services: Qualitative Assessment of Kenyan Provider Experiences.

BACKGROUND: Literature suggests that electronic health (eHealth) interventions can improve the efficiency and accuracy of health service delivery and improve health outcomes and are generally well received by patients; however, there are limited data on provider experiences using eHealth interventions in resource-limited settings. The HIV Infant Tracking System (HITSystem) is an eHealth intervention designed to improve early infant diagnosis (EID) outcomes among HIV-exposed infants. OBJECTIVE: We aimed to compare provider experiences with standard EID and HITSystem implementation at 6 Kenyan hospitals and 3 laboratories. The objective of this study was to better understand provider experiences implementing and using the HITSystem in order to assess facilitators and barriers that may impact adoption and sustainability of this eHealth intervention. METHODS: As part of a randomized controlled trial to evaluate the HITSystem, we conducted semistructured interviews with 17 EID providers at participating intervention and control hospitals and laboratories. RESULTS: Providers emphasized the perceived usefulness of the HITSystem, including improved efficiency in sample tracking and patient follow-up, strengthened communication networks among key stakeholders, and improved capacity to meet patient needs compared to standard EID. These advantages were realized from an intervention that providers saw as easy to use and largely compatible with workflow. However, supply stock outs and patient psychosocial factors (including fear of HIV status disclosure and poverty) provided ongoing challenges to EID service provision. Furthermore, slow or sporadic internet access and heavy workload prevented real-time HITSystem data entry for some clinicians. CONCLUSIONS: Provider experiences with the HITSystem indicate that the usefulness of the HITSystem, along with the ease with which it is able to be incorporated into hospital workflows, contributes to its sustained adoption and use in Kenyan hospitals. To maximize implementation success, care should be taken in intervention design and implementation to ensure that end users see clear advantages to using the technology and to account for variations in workflows, patient populations, and resource levels by allowing flexibility to suit user needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02072603; https://clinicaltrials.gov/ct2/show/NCT02072603 (Archived by WebCite at http://www.webcitation.org/71NgMCrAm).

An in vitro evaluation of drugs used in the Kenyan ART program.

The majority of anti-HIV drug susceptibility tests have been performed on subtype B HIV-1 strains, since these are the most prevalent in countries designing, testing, and manufacturing the current anti-HIV agents. The increasing global spread of HIV subtype highlights the need to determine the activity of anti-HIV drugs against subtypes of HIV other than subtype B. Furthermore an increasing number of individuals infected with many of the non subtype B virus strains now receive antiretroviral therapy because of rollout programs in developing countries as well as increasing migration to the developed world. The phenotypic susceptibility of two laboratory strains HIV-1JFRL and HIV-1IIIB (representing subtype B) and two clinical isolates HIV-104RTA and HIV-1025RTA (representing subtypes A and D respectively) was determined. The in vitro drug susceptibility testing of the isolates was carried out in C8166 cell line and in peripheral blood mononuclear cells (PBMCs). The study revealed that the drugs used in the Kenyan national ART program inhibited HIV-1 replication in-vitro as their inhibitory concentrations (IC50) compared well with the standard Inhibitory concentration values. The results also suggest a biochemical similarity of the reverse transcriptase (RT) and protease enzymes from these subtypes despite the divergence at the genetic level. The findings suggest that similar clinical benefits of antiviral therapy obtain in persons infected with other subtypes of HIV-1other than subtype B and that the generic drugs used in the national ART program in Kenya are as efficacious as branded drugs in inhibiting HIV replication in vitro despite the limited number of the viruses studied.

Prevalence, awareness and risk factors associated with Hepatitis B infection among pregnant women attending the antenatal clinic at Mbagathi District Hospital in Nairobi, Kenya.

INTRODUCTION: Hepatitis B Viral Infection (HBV) remains one of the leading cause of morbidity and mortality globally accounting for 38-53% of chronic liver diseases and about 686,000 deaths annually. The prevalence of HBV is 9-20% in Sub-Saharan Africa, and in Kenya it is 5-30% among the general population and 9.4% among pregnant women. This study was aimed at identifying the prevalence, awareness and risk factors associated with HBV infections among pregnant women attending Antenatal clinic (ANC) at Mbagathi District hospital, Nairobi. METHODS: This was a cross-sectional study involving 287 pregnant women enrolled for three months (September to December 2014) from Nairobi and neighbouring counties. A structured questionnaire that captured social, demographic and explanatory variables was administered to the study participants. Blood samples were also drawn from the participants and tested for HBV using Enzyme-Linked Immunosorbent Assay (ELISA) system. RESULTS: The study established that the prevalence of HBV infections among pregnant women attending antenatal clinic at Mbagathi District Hospital was 3.8% with highest infection rate among the 20-24 years age group. Seventy six (60.8 %) of the participants reported sexual encounters in less than a month before the interview of which 5 (7.6%) reported encounters involving other partners apart from their spouses. HBV awareness among the study participants was 12.2%. Before the interview, those with at least tertiary education (Mean =1.33, SD = 1.131), were more informed about HBV infection as compared to those with primary and secondary education (Mean = 0.63, SD = 0.722; (Mean =0.31, SD= 0.664). In regards to assessment of the risk factors; type of family (χ² =19.753 df2 p<0.01), parity (χ² =7.128 df2 p<0.01), History of abortions (χ²=9.094 df1 p<0.01), early age (11-15 years) at first sexual encounter (χ² =8.185 df1 p<0.01) were significantly associated with HBV positivity. CONCLUSION: The prevalence of HBV infection among pregnant women attending Antenatal clinic (ANC) at Mbagathi District hospital, Nairobi was lower (3.8%) than the prevalence among pregnant women nationally (9.4%). These women also showed a low level of HBV awareness (12.2%.).

Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children.

OBJECTIVES: Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children. METHODS: Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at <5 years of age (rapid progressors; RP), and 32 (17 male/15 female) who started at >10 years of age (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and the HLA class I-related epitopes were compared between the two groups. RESULTS: Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20% of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3 region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A*74:01, A*32:01 and A*26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B*45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP. CONCLUSIONS: Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children.

Co-Infection Burden of Hepatitis C Virus and Human Immunodeficiency Virus among Injecting Heroin Users at the Kenyan Coast.

BACKGROUND: Injection drug use is steadily rising in Kenya. We assessed the prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast. METHODS: A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation center program in Malindi were consented and screened for HIV-1 and HCV by serology and PCR and their CD4 T-cells enumerated by FACS. RESULTS: Prevalence of HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%) were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co-infection was higher among injectors aged 30 to 40 years (20.7%) and among males (22.1%) than comparable groups. About 35% of the injectors were receiving antiretroviral treatment (ART). Co-infection was highest among injectors receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3 overall, significantly lower for co-infected (mean, 146; 95% CI 114 - 179 cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 - 487 cells/mm3, p<0.001) or uninfected (mean, 618, 95% CI 549 - 687 cells/mm3, p<0.001) injectors and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 - 156 cells/mm3) than TDF (mean 607, 95% CI, 196 - 1018 cells/mm3, p=0.005) or AZT (mean 474, 95% CI -377 - 571 cells/mm3, p=0.004). CONCLUSION: Mono and dual infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is low. The co-infected IHUs have elevated risk of immunodeficiency due to significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as-prevention for both HIV and HCV and harm reduction should be scaled up to alleviate infection burden.