Point-of-Care Early Infant Diagnosis Improves Adherence to the Testing Algorithm in Kenya.

INTRODUCTION: We determine the level of adherence to the revised Kenya early infant diagnosis (EID) algorithm during implementation of a point-of-care (POC) EID project. METHODS: Data before (August 2016 to July 2017) and after (August 2017 to July 2018) introduction of POC EID were collected retrospectively from the national EID database and registers for 33 health facilities. We assessed the number of HIV-infected infants who underwent confirmatory testing and received baseline viral load test and proportion of infants with an initial negative result who had a subsequent test. RESULTS AND DISCUSSION: Significantly higher number of infants accessed confirmatory testing (94.2% versus 38.6%; P < .0001) with POC EID. Baseline viral load test and follow-up testing at 6 months, although higher with POC EID, were not significantly different from the pre-POC EID intervention period. CONCLUSION: The POC EID implementation has the potential to increase proportion of infants who receive confirmatory testing, thus reducing the risk of false-positive results.

Assessing treatment outcomes among peer educators living with HIV in Kenya.

BACKGROUND: People living with HIV (PLHIV) often face barriers in accessing quality and comprehensive HIV care, including stigma and discrimination, which results in poor retention and viral non-suppression. Peer-led interventions can help address these barriers. In Kenya, peer educators (PEs) are PLHIV who support other PLHIV to adhere to clinic schedules and antiretroviral medication uptake. In spite of their status as role models and their key role in supporting clients receiving HIV care and treatment, little is known about the characteristics and treatment outcomes of PEs themselves, specifically viral suppression. METHODS: This is a retrospective descriptive analysis of program data on treatment outcomes of PEs engaged in active patient support activities between October 2010 and January 2017. All eligible PEs from 140 health facilities located in 23 counties of Kenya were included in the study. Data from 230 PEs were abstracted from the electronic medical records, patient files, and registers between June and August 2017. Study variables included key sociodemographic characteristics (sex, marital status, and age), duration on antiretroviral therapy (ART), WHO clinical staging, baseline CD4 count, current antiretroviral regimen and uptake of isoniazid preventive therapy (IPT). The outcome variable was viral suppression, defined as a viral load <1000 copies/ml. RESULTS: Overall, 173/230 (75%) of the PEs were female, 144/230 (63%) were married, and median age (LQ, UQ) was 38.5 (33.0, 42.0) years. The PEs had been on ART for a median (LQ, UQ) duration of 76.0 (37.0, 105.0) months. Six months IPT completion was high at 97%. Of the 222 (97%) PEs with an up-to-date viral load taken within the last one year, 211 (95%) were virally suppressed. CONCLUSION: Our study showed that peer educators actively engaged in patient support activities have achieved high viral suppression rates.

Optimizing linkage to care and initiation and retention on treatment of adolescents with newly diagnosed HIV infection.

OBJECTIVE: Unsuccessful linkage to care and treatment increases adolescent HIV-related morbidity and mortality. This study evaluated the effect of a novel adolescent and youth Red Carpet Program (RCP) on the timing and outcomes of linkage to care. DESIGN: A prepost implementation evaluation of the pilot RCP program. SETTINGS: Healthcare facilities (HCFs) and schools in Homa Bay County, Kenya. STUDY PARTICIPANTS: HIV-infected adolescents (15-19 years) and youth (20-21 years). INTERVENTIONS: RCP provided fast-track peer-navigated services, peer counseling, and psychosocial support at HCFs and schools in six Homa Bay subcounties in 2016. RCP training and sensitization was implemented in 50 HCFs and 25 boarding schools. MAIN OUTCOME MEASURES: New adolescent and youth HIV diagnosis, linkage to and retention in care and treatment. RESULTS: Within 6 months of program rollout, 559 adolescents and youths (481 women; 78 men) were newly diagnosed with HIV (15-19 years n = 277; 20-21 years, n = 282). The majority (n = 544; 97.3%) were linked to care, compared to 56.5% at preimplementation (P < 0.001). All (100.0%; n = 559) adolescents and youths received peer counseling and psychosocial support, and the majority (n = 430; 79.0%) were initiated on treatment. Compared to preimplementation, the proportion of adolescents and youths who were retained on treatment increased from 66.0 to 90.0% at 3 months (P < 0.001), and from 54.4 to 98.6% at 6 months (P < 0.001). CONCLUSION: Implementation of RCP was associated with significant improvement in linkage to and early retention in care among adolescent and youth. The ongoing study will fully assess the efficacy of this linkage-to-care approach.

Cluster-Randomized Controlled Study of SMS Text Messages for Prevention of Mother-to-Child Transmission of HIV in Rural Kenya.

Background. Antiretroviral medications are key for prevention of mother-to-child transmission (PMTCT) of HIV, and transmission mitigation is affected by service delivery, adherence, and retention. Methods. We conducted a cluster-randomized controlled study in 26 facilities in Nyanza, Kenya, to determine the efficacy of SMS text messages on PMTCT outcomes. The relative risk and confidence intervals were estimated at the facility level using STATA. Results. 550 women were enrolled, from June 2012 to July 2013. The median age was 25.6 years, and 85.3% received ARVs. Maternal ARV use was similar between the intervention and control arms: 254/261 (97.3%) versus 241/242 (99.6%) at 34-36 weeks of gestation and 234/247 (94.7%) versus 229/229 (100%) at delivery. Among infants, 199/246 (80.9%) and 209/232 (90.1%) received ARVs (RR: 0.91; 95% CI: 0.77-1.14); 88% versus 88.6% were tested for HIV at 6 weeks, with 1/243 (0.4%) and 3/217 (1.4%) positive results in the intervention and control arms, respectively. Communication increased in both the intervention and control arms, with the mean number of 7.5 (SD: 5.70) compared with 6 (SD: 9.96), p < 0.0001. Conclusions. We identified high ARV uptake and infant HIV testing, with very low HIV transmission. Increased communication may influence health-seeking behaviors irrespective of technology. The long-term effectiveness of facilitated communication on PMTCT outcomes needs to be tested. The study has been registered on ClinicalTrials.gov under the identifier NCT01645865.

Provision of services and care for HIV-exposed infants: a comparison of maternal and child health clinic and HIV comprehensive care clinic models.

OBJECTIVE: Prevention of Mother-to-Child Transmission of HIV programs require follow-up of HIV-exposed infants (HEI) for infant feeding support, prophylactic medicines, and HIV diagnosis for at least 18 months. Retention in care and receipt of HIV services are challenging in resource-limited settings. This study compared infant follow-up results when HEI services were provided within Maternal and Child Health (MCH) clinics or in specialized HIV Comprehensive Care Clinics (CCCs) in Kenya. METHODS: This observational prospective cohort study enrolled HEI at 6-8 weeks of age in 2 purposively selected hospitals with similar characteristics but different models of service delivery. In the CCC model, HEI received immunization and growth monitoring in MCH but cotrimoxazole prophylaxis and infant HIV testing in the CCC. In the MCH model, all services were provided in the MCH. Data were collected at enrollment, 14 weeks, and 6, 9, and 12 months. RESULTS: From April 2008 to April 2009, 184 HEI were enrolled in the CCC cohort and 179 in the MCH cohort. Infants in MCH were 1.14, 1.42, 1.95, and 1.29 times more likely to attend 14-week, 6-, 9-, and 12-month postnatal visits, respectively, and 2.24 times (95% confidence interval: 1.57 to 3.18) more likely to attend all 4 visits. Although infants in MCH were 1.33 times (95% confidence interval: 1.10 to 1.62) more likely to have HIV antibody testing at 1 year than CCC, there were no differences for polymerase chain reaction test or cotrimoxazole initiation at 6-8 weeks. CONCLUSIONS: HIV services integrated in MCH yield better follow-up of HEI than CCC.

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa.

The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.

Characterization of CD8 T-cell responses in HIV-1-exposed seronegative commercial sex workers from Nairobi, Kenya.

CD8+ T-lymphocyte responses are crucial to the control of HIV-1; therefore, studying the CD8+ immune response in a naturally resistant population could provide valuable insights into an effective anti-HIV response in healthy uninfected individuals. Approximately 5-10% of the women in the Pumwani Commercial Sex Worker cohort in Nairobi, Kenya, have been highly exposed to HIV-1 yet remain HIV-IgG-seronegative and HIV-PCR negative (HIV(ES)). As IFN-gamma production correlates to cytotoxic function, the CD8+ T-lymphocyte IFN-gamma response to HIV p24 peptides was compared in HIV(ES) and HIV-infected (HIV+) individuals. Almost 40% of the HIV(ES) had a CD8+ IFN-gamma+ response that was five times lower in magnitude than that of the HIV+ group. The breadth of the response in HIV(ES) was very narrow and focused primarily on one peptide that is similar to the protective KK10 peptide. In the HIV+ group, low peripheral CD4+ counts negatively influenced the number of CD8+ cells producing IFN-gamma, which may undermine the ability to control HIV. Overall, many of the HIV(ES) women possess a HIV-1 p24-specific CD8+ IFN-gamma response, providing evidence to the specificity needed for an effective HIV vaccine.

IL-7Ralpha expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation.

Many factors can influence the rate of HIV disease progression, including those that maintain T cell homeostasis. One key homeostatic regulator is the IL-7 receptor (IL-7R). Previous studies have shown IL-7R expression levels decrease in HIV infection, but effects on memory subtypes, CD4(+) T cells, and cell function have not been explored. The present study examined the expression of the IL-7Ralpha chain on naïve and memory T lymphocyte subsets of both HIV-positive and HIV-negative individuals from Nairobi, Kenya to assess the role of IL-7Ralpha in HIV disease. Expression of IL-7Ralpha was significantly reduced in all CD4(+) and CD8(+) T cell subsets in HIV-positive individuals. This reduction was further enhanced in those with advanced HIV progression. Expression of IL-7Ralpha was inversely correlated to immune activation, and apoptosis, and was positively correlated with CD4 count in both bivariate and multivariate analysis. Expression of IL-7Ralpha did not correlate with HIV viral loads, indicating the elevated immune activation seen in HIV-infected individuals may be impacting expression of IL-7Ralpha, independent of viral loads. Signaling via the IL-7R is essential for T cell homeostasis and maintenance of T cell memory. Reduction of this receptor may contribute to the homeostatic disruption seen in HIV.

CD4+ T cell responses in HIV-exposed seronegative women are qualitatively distinct from those in HIV-infected women.

The immune response of human immunodeficiency virus (HIV)-exposed seronegative (ESN) women may be qualitatively different from that in those infected with HIV (HIV(+)). In a cohort of female commercial sex workers in Nairobi, Kenya, we found significantly lower (P< or =.01) levels of CD4(+)-specific immune activation and apoptosis in the ESN women compared with those in the HIV(+) women. Compared with the HIV(+) women, a lower proportion of the ESN women showed p24 peptide pool responses by the short-term, CD4(+)-specific, interferon (IFN)- gamma intracellular cytokine staining assay, whereas the proportion showing responses by the long-term, CD8(+)-depleted T cell proliferation assay was similar. Interestingly, the ESN responders had a 4.5-fold stronger proliferation response (P=.002) than the HIV(+) group. These data suggest that, compared with those in HIV(+) women, CD4(+) T cells in ESN women have a much greater ability to proliferate in response to p24 peptides.

Cross-clade CD8(+) T-cell responses with a preference for the predominant circulating clade.

Human immunodeficiency virus (HIV) genetic diversity is a major impediment to the design of a successful vaccine. Even if an HIV vaccine is proven effective, it remains to be seen whether this protection will extend to inter-clade, intra-clade, and recombinant strains. We used recombinant vaccinia-based interferon gamma (IFN) Elispot assays to test the inter-clade crossreactivity of clades A, B, C, and D HIV Env in two cohorts of HIV-infected Kenyans. Despite the tremendous diversity in this HIV protein, a substantial proportion of multi-clade responses were observed. Although these multi-clade responses correlated well with each other in regression analyses, clade A responses were seen at a higher frequency and at greater relative magnitudes in a proportion of these patients, when compared to the other three clades. Epitope mapping indicates CD8(+) T cell recognition of conserved regions of Env, accounting for the high degree of cross-reactivity but not the clade A preference. A better understanding of cross-clade CD8(+) T cell responses to HIV may help to predict whether a successful vaccine could be used to stop geographically and genetically distinct HIV epidemics.

Elevation of immune activation in kenyan women is associated with alterations in immune function: implications for vaccine development.

The infectious burden leading to immune activation can vary between different populations and lead to various immune dysfunctions. We compared the effect of immune activation on apoptosis and T cell function in HIV uninfected individuals from Nairobi, Kenya (n=34), and Winnipeg, Canada (n=10). Women from Nairobi had a significantly greater number of CD8+ T cells expressing the activation markers CD38 and HLA DR. Kenyan women also had significantly higher levels of CTLA-4+ CD4 and CD8+ T cells, and reduced levels of CD28+ CD8+ cells. Levels of CD95+ CD4+ T cells were higher in Kenyan women and, correspondingly, showed higher levels of spontaneous apoptosis. Kenyan women also demonstrated hyper-responsiveness to T cell activation as assessed by interferon gamma production. This study demonstrates that in a population of Kenyan women with high levels of T cell activation, there were also elevated levels of T cell apoptotic death and hyper-responsiveness. These differences may influence the efficacy of immune responses to pathogens and must be considered when testing candidate vaccines.