Understanding the levels and associated factors of non-adherence to antiretroviral therapy (ART) is crucial in designing interventions to improve adherence and health outcomes of ART. We assessed ...non-adherence to ART among HIV-infected persons reporting ART use in a nationally representative survey in Kenya.
The Kenya AIDS Indicator Survey 2012 was a population-based, household survey of persons aged 18 months-64 years conducted in 2012-2013. Self-reported information was collected on demographics, sexual behaviour, HIV status, and ART use. Blood was collected for HIV testing, and if HIV infected, CD4 and viral load testing. HIV-positive specimens were tested for the presence of antiretroviral (ARV) drugs using a qualitative ARV assay using liquid chromatography-tandem mass spectrometry. HIV-positive persons who reported receiving ART but did not have the ARV biomarker present were defined as being non-adherent to their ARV medication. We restricted our analysis to HIV-infected persons aged 15-64 years who reported receiving ART and had laboratory-confirmed results from ARV testing. Multivariate logistic regression was used to identify variables associated with non-adherence.
A total of 648 (5.6%; CI 4.9-6.3) tested HIV-positive of whom 559 (86.3%) had sufficient volume of blood to be tested for ARV drugs. Of those, 271 (47.7%; CI 41.8-53.6) self-reported HIV-positive status during the interview and 186 (69.1%; CI 62.2-76.0) of those reported taking ART. The ARV biomarker was absent in 18 of 186 individuals (9.4%; CI 4.9-13.8) who thus were defined as being non-adherent to ART. Non-adherence was associated with being aged 15-29 years (AOR 8.39; CI 2.26-31.22, p = 0.002) compared to aged 30-64 years, rural residence (AOR 5.87; CI 1.39-25.61, p = 0.016) compared with urban residence and taking recreational drugs in the past 30 days (AOR 5.89; CI 1.30-26.70, p = 0.022).
Overall, less than 10% of Kenyans aged 15-64 years on ART were not adhering to their HIV medication, highlighting the success of the Kenyan national ART program. Our findings, however, point to the need for targeted interventions particularly for young persons, those in rural areas to improve adherence outcomes, as well as delivery of treatment programs that include psychosocial support as a preventative measure to minimize substance abuse and the risk of treatment failure.
The current World Health Organization (WHO) pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. Identifying factors altering the exposure of these drugs in children is ...essential for dose optimization. Pediatric pharmacokinetic studies are usually small, leading to high variability and uncertainty in pharmacokinetic results between studies. We pooled data from large pharmacokinetic studies to identify key covariates influencing drug exposure to optimize tuberculosis dosing in children.
We used nonlinear mixed-effects modeling to characterize the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide, and investigated the association of human immunodeficiency virus (HIV), antiretroviral therapy (ART), drug formulation, age, and body size with their pharmacokinetics. Data from 387 children from South Africa, Zambia, Malawi, and India were available for analysis; 47% were female and 39% living with HIV (95% on ART). Median (range) age was 2.2 (0.2 to 15.0) years and weight 10.9 (3.2 to 59.3) kg. Body size (allometry) was used to scale clearance and volume of distribution of all 3 drugs. Age affected the bioavailability of rifampicin and isoniazid; at birth, children had 48.9% (95% confidence interval (CI) 36.0%, 61.8%; p < 0.001) and 64.5% (95% CI 52.1%, 78.9%; p < 0.001) of adult rifampicin and isoniazid bioavailability, respectively, and reached full adult bioavailability after 2 years of age for both drugs. Age also affected the clearance of all drugs (maturation), children reached 50% adult drug clearing capacity at around 3 months after birth and neared full maturation around 3 years of age. While HIV per se did not affect the pharmacokinetics of first-line tuberculosis drugs, rifampicin clearance was 22% lower (95% CI 13%, 28%; p < 0.001) and pyrazinamide clearance was 49% higher (95% CI 39%, 57%; p < 0.001) in children on lopinavir/ritonavir; isoniazid bioavailability was reduced by 39% (95% CI 32%, 45%; p < 0.001) when simultaneously coadministered with lopinavir/ritonavir and was 37% lower (95% CI 22%, 52%; p < 0.001) in children on efavirenz. Simulations of 2010 WHO-recommended pediatric tuberculosis doses revealed that, compared to adult values, rifampicin exposures are lower in most children, except those younger than 3 months, who experience relatively higher exposure for all drugs, due to immature clearance. Increasing the rifampicin doses in children older than 3 months by 75 mg for children weighing <25 kg and 150 mg for children weighing >25 kg could improve rifampicin exposures. Our analysis was limited by the differences in availability of covariates among the pooled studies.
Children older than 3 months have lower rifampicin exposures than adults and increasing their dose by 75 or 150 mg could improve therapy. Altered exposures in children with HIV is most likely caused by concomitant ART and not HIV per se. The importance of the drug-drug interactions with lopinavir/ritonavir and efavirenz should be evaluated further and considered in future dosing guidance.
ClinicalTrials.gov registration numbers; NCT02348177, NCT01637558, ISRCTN63579542.
The number of youth and adolescents (10-24 years) with HIV infection has increased substantially presenting unique challenges to effective health service delivery.
We examined routinely collected ...patient-level data for antiretroviral treatment (ART)-naive HIV-infected patients, aged 10-24 years, enrolled in care during 2006-2011 at 109 ICAP-supported health facilities in three provinces in Kenya. Loss to follow-up (LTF) was defined as having no clinic visit for 12 months prior to ART initiation (pre-ART) and 6 months for ART patients. Competing risk and Kaplan-Meier estimators were used to calculate LTF and death rates. Sub-distributional and Cox proportional-hazards models were used to identify potential predictors of death and LTF.
Overall 22 832 patients were enrolled in care at 10-24 years of age, 69.5% were aged 20-24 years, and 82% were female. Median CD4(+) cell count was 332 cells/μl (interquartile range 153-561); 70.8% were WHO stage I/II. Young adolescents (10-14 years) had more advanced WHO stage and lower median CD4(+) cell count compared to youth (15-24 years) at enrollment (284 vs. 340 cells/μl; P < 0.0001). Cumulative incidence of LTF and death at 24 months for pre-ART patients was 46.1% 95% confidence interval (CI) 45.4-46.8%) and 2.1% (95% CI 1.9-2.3%), respectively. For those on ART, 32.2% (95% CI 31.1-33.3%) were LTF and 3.9% (95% CI 1.7-2.3%) died within 24 months. LTF among pre-ART and ART patients was twice as high among youth compared to young adolescents.
LTF of young people with HIV in this Kenyan cohort was high and notably greater among youth compared to young adolescents. Novel strategies targeting these populations are urgently needed to improve retention.
Over the last decade, the Kenyan HIV treatment program has grown exponentially, with improved survival among people living with HIV (PLHIV). In the same period, noncommunicable diseases (NCDs) have ...become a leading contributor to disease burden. We sought to characterize the burden of four major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes mellitus) among adult PLHIV in Kenya.
We conducted a nationally representative retrospective medical chart review of HIV-infected adults aged ≥15 years enrolled in HIV care in Kenya from October 1, 2003 through September 30, 2013. We estimated proportions of four NCD categories among PLHIV at enrollment into HIV care, and during subsequent HIV care visits. We compared proportions and assessed distributions of co-morbidities using the Chi-Square test. We calculated NCD incidence rates and their confidence intervals in assessing cofactors for developing NCDs.
We analyzed 3170 records of HIV-infected patients; 2115 (66.3%) were from women. Slightly over half (51.1%) of patient records were from PLHIVs aged above 35 years. Close to two-thirds (63.9%) of PLHIVs were on ART. Proportion of any documented NCD among PLHIV was 11.5% (95% confidence interval CI 9.3, 14.1), with elevated blood pressure as the most common NCD 343 (87.5%) among PLHIV with a diagnosed NCD. Despite this observation, only 17 (4.9%) patients had a corresponding documented diagnosis of hypertension in their medical record. Overall NCD incidence rates for men and women were (42.3 per 1000 person years 95% CI 35.8, 50.1 and 31.6 95% CI 27.7, 36.1, respectively. Compared to women, the incidence rate ratio for men developing an NCD was 1.3 95% CI 1.1, 1.7, p = 0.0082). No differences in NCD incidence rates were seen by marital or employment status. At one year of follow up 43.8% of PLHIV not on ART had been diagnosed with an NCD compared to 3.7% of patients on ART; at five years the proportions with a diagnosed NCD were 88.8 and 39.2% (p < 0.001), respectively. CONCLUSIONS: PLHIV in Kenya have a high prevalence of NCD diagnoses. In the absence of systematic, effective screening, NCD burden is likely underestimated in this population. Systematic screening and treatment for NCDs using standard guidelines should be integrated into HIV care and treatment programs in sub-Saharan Africa.
HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where ...HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.
Pregnant women and children living with HIV in Kenya achieve viral suppression (VS) at lower rates than other adults. While many factors contribute to these low rates, the acquisition and development ...of HIV drug resistance mutations (DRMs) are a contributing factor. Recognizing the significance of DRMs in treatment decisions, resource-limited settings are scaling up national DRM testing programs. From provider and patient perspectives, however, optimal ways to operationalize and scale-up DRM testing in such settings remain unclear.
Our mixed methods study evaluates the attitudes towards, facilitators to, and barriers to DRM testing approaches among children and pregnant women on antiretroviral therapy (ART) in five HIV treatment facilities in Kenya. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with adolescents, caregivers, pregnant women newly initiating ART or with a high viral load, and providers, laboratory/facility leadership, and policy makers. Our KII guides covered the following domains: (1) DRM testing experiences in routine care and through our intervention and (2) barriers and facilitators to routine and point-of-care DRM testing scale-up. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes.
The following themes emerged from our analysis: (1) DRM testing and counseling were valuable to clinical decision-making and reassuring to patients, with timely results allowing providers to change patient ART regimens faster; (2) providers and policymakers desired an amended and potentially decentralized DRM testing process that incorporates quicker sample-to-results turn-around-time, less burdensome procedures, and greater patient and provider "empowerment" to increase comfort with testing protocols; (3) facility-level delays, deriving from overworked facilities and sample tracking difficulties, were highlighted as areas for improvement.
DRM testing has the potential to considerably improve patient health outcomes. Key informants recognized several obstacles to implementation and desired a more simplified, time-efficient, and potentially decentralized DRM testing process that builds provider comfort and confidence with DRM testing protocols. Further investigating the implementation, endurance, and effectiveness of DRM testing training is critical to addressing the barriers and areas of improvement highlighted in our study.
NCT03820323.
Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum ...women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed.
We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes.
Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing's faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders.
The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs.
NCT03820323, 29/01/2019.
Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated ...in public HIV care clinics in Kenya.
As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010.
After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25–39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2–39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation.
We observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible.
National Institute of Mental Health and Bill & Melinda Gates Foundation.
To assess changes and equity in antiretroviral therapy (ART) use in Kenya and South Africa.
We analysed national population-based household surveys conducted in Kenya and South Africa between 2007 ...and 2012 for factors associated with lack of ART use among people living with HIV (PLHIV) aged 15-64 years. We considered ART use to be inequitable if significant differences in use were found between groups of PLHIV (e.g. by sex).
ART use among PLHIV increased from 29.3% (95% confidence interval CI: 22.8-35.8) to 42.5% (95%CI: 37.4-47.7) from 2007 to 2012 in Kenya and 17.4% (95%CI: 14.2-20.9) to 30.3% (95%CI: 27.2-33.6) from 2008 to 2012 in South Africa. In 2012, factors independently associated with lack of ART use among adult Kenyan PLHIV were rural residency (adjusted odds ratio aOR 1.98, 95%CI: 1.23-3.18), younger age (15-24 years: aOR 4.25, 95%CI: 1.7-10.63, and 25-34 years: aOR 5.16, 95%CI: 2.73-9.74 versus 50-64 years), nondisclosure of HIV status to most recent sex partner (aOR 2.41, 95%CI: 1.27-4.57) and recent recreational drug use (aOR 2.50, 95%CI: 1.09-5.77). Among South African PLHIV in 2012, lack of ART use was significantly associated with younger age (15-24 years: aOR 4.23, 95%CI: 2.56-6.70, and 25-34 years: aOR 2.84, 95%CI: 1.73-4.67, versus 50-64 years), employment status (aOR 1.61, 95%CI: 1.16-2.23 in students versus unemployed), and recent recreational drug use (aOR 4.56, 95%CI: 1.79-11.57).
Although we found substantial increases in ART use in both countries over time, we identified areas needing improvement including among rural Kenyans, students in South Africa, and among young people and drug users in both countries.
In 2017, the Kenyan Ministry of Health integrated provision of pre-exposure prophylaxis (PrEP) into public HIV-1 care clinics as a key component of the national HIV-1 prevention strategy. Estimates ...of the cost of PrEP provision are needed to inform the affordability and cost-effectiveness of PrEP in Kenya.
We conducted activity-based micro-costing from the payer perspective to estimate both the financial and economic costs of all resources and activities required to provide PrEP in Kenya's public sector. We estimated total and unit costs in 2019 United States dollars from a combination of project expense reports, Ministry of Health training reports, clinic staff interviews, time-and-motion observations, and routinely collected data from PrEP recipient files from 25 high-volume HIV-1 care clinics.
In the first year of programmatic PrEP delivery in 25 HIV-1 care clinics, 2,567 persons initiated PrEP and accrued 8,847 total months of PrEP coverage, accounting for 2 % of total outpatient clinic visits. The total financial cost to the Ministry of Health was $91,175, translating to an average of $10.31 per person per month. The majority (69 %) of financial costs were attributable to PrEP medication, followed by administrative supplies (17 %) and training (9 %). Economic costs were higher ($188,584 total; $21.32 per person per month) due to the inclusion of the opportunity cost of staff time re-allocated to provide PrEP and a proportional fraction of facility overhead. The vast majority (88 %) of the annual $80,811 economic cost of personnel time was incurred during activities to recruit new clients (e.g., discussion of PrEP within HIV-1 testing and counselling services), while the remaining 12 % was for activities related to both initiation and maintenance of PrEP provision (e.g., client consultations, technical advising, support groups).
Integration of PrEP provision into existing public health HIV-1 care service delivery platforms resulted in minimal additional staff burden and low incremental costs. Efforts to improve the efficiency of PrEP provision should focus on reductions in the cost of PrEP medication and extra-clinic demand creation and community sensitization to reduce personnel time dedicated to recruitment-related activities.
ClinicalTrials.gov registration NCT03052010 . Retrospectively registered on February 14, 2017.
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