SummaryBackgroundAntiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART.MethodsThe TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.FindingsWe included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count <100 cells per μL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1·48, 95% CI 1·20–1·82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0·626]).InterpretationWe recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial.FundingThe Wellcome Trust.

Background The number of youth and adolescents (10–24 years) with HIV infection has increased substantially presenting unique challenges to effective health service delivery. Methods 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. Results 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. Conclusion 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.

Introduction:Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation – especially HIV incidence, population viral load, and ART eligibility – is rare in sub-Saharan Africa.Design/methods:To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15–59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4+ cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections.Results:Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0–25.2] and 1.9 new cases/100 person-years (95% CI 1.1–2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8–61.9) were previously diagnosed, 53.1% (95% CI 50.5–55.7) were receiving care, and 39.7% (95% CI 37.1–42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3–62.7) to 82.0% (95% CI 79.5–84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4+ cell count (500–749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20–0.60, P < 0.01).Conclusion:This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.

Background While advances have been made in HIV prevention and treatment, new HIV infections continue to occur. The introduction of pre-exposure prophylaxis (PrEP) as an additional HIV prevention option for those at high risk of HIV may change the landscape of the HIV epidemic, especially in sub-Saharan Africa, which bears the greatest HIV burden. Methods: This paper details Kenya’s experience of PrEP rollout as a national public sector program. The process of a national rollout of PrEP guidance, partnerships, challenges, lessons learnt and progress related to national scale up of PrEP in Kenya, as of 2018, is described. National rollout of PrEP was strongly lead by the government, and work was executed through a multidisciplinary, multi-organisation dedicated team. This required reviewing available evidence, providing guidance to health providers, integration into existing logistic and health information systems, robust communication and community engagement. Mapping of the response showed that subnational levels had existing infrastructure but required targeted resources to catalyse PrEP provision. Rollout scenarios were developed and adopted, with prioritisation of 19 counties focusing on high incidence area and high potential PrEP users to maximise impact and minimise costs. Results: PrEP is now offered in over 900 facilities countrywide. There are currently over 14000 PrEP users 1 year after launching PrEP.Conclusions: Kenya becomes the first African country to rollout PrEP as a national program, in the public sector. This case study will provide guidance for low- and middle-income countries planning the rollout of PrEP in response to both generalised and concentrated epidemics.

Background 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. Methods 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. Results 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.