Gaps in the Child Tuberculosis Care Cascade in 32 Rural Communities in Uganda and Kenya.

Background:Reducing tuberculosis (TB) deaths among children requires a better understanding of the gaps in the care cascade from TB diagnosis to treatment completion. We sought to assess the child TB care cascade in 32 rural communities in Uganda and Kenya using programmatic data. Methods:This is a retrospective cohort study of 160,851 children (ages <15 years) living in 12 rural communities in Kenya and 22 in Uganda. We reviewed national TB registries from health centers in and adjacent to the 32 communities, and we included all child TB cases recorded from January 1, 2013 to June 30, 2016. To calculate the first step of the child TB care cascade, the number of children with active TB, we divided the number of reported child TB diagnoses by the 2015 World Health Organization (WHO) child TB case detection ratio for Africa of 27%. The remaining components of the Child TB Care Cascade were ascertained directly from the TB registries and included: diagnosed with TB, started on TB treatment, and completed TB treatment. Results:In two and a half years, a total of 42 TB cases were reported among children living in 32 rural communities in Uganda and Kenya. 40% of the children were co-infected with HIV. Using the WHO child TB case detection ratio, we calculated that 155 children in this cohort had TB during the study period. Of those 155 children, 42 were diagnosed and linked to TB care, 42 were started on treatment, and 31 completed treatment. Among the 42 children who started TB treatment, reasons for treatment non-completion were loss to follow up (7%), death (5%), and un-recorded reasons (5%). Overall, 20% (31/155) of children completed the child TB care cascade. Conclusion:In 32 rural communities in Uganda and Kenya, we estimate that 80% of children with TB fell off the care cascade. Reducing morbidity and mortality from child TB requires strengthening of the child TB care cascade from diagnosis through treatment completion

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

BackgroundAs sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.MethodsThe Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged ≥15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.FindingsBetween April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90·3%), of whom 132 030 (48·2%) were adults. Of these, 117 711 (89·2%) had their HIV status established, of whom 11 964 (10·2%) were HIV positive. Of these, we measured viral load in 8828 (73·8%) people. Viral suppression occurred in 3427 (81·6%) of 4202 HIV-positive adults on ART and 4490 (50·9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48·2%) of 1827 people in west Uganda, 516 (45·0%) of 1147 in east Uganda, and 3093 (52·8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2·9%) of 16 874 couples were serodiscordant: in 287 (58·3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14·0%], viral load was >100 000 copies per mL). In Kenya, 859 (10·0%) of 8616 couples were serodiscordant: in 445 (53·0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).InterpretationBefore the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.FundingNational Institute of Allergy and Infectious Diseases (National Institutes of Health) and the President's Emergency Plan for AIDS Relief

Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy.

BACKGROUND: Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir (LPV/r) or non nucleoside reverse transcription inhibitor-based ART. METHODS: HIV-infected children 2 months to 6 years of age were randomized to LPV/r- or non nucleoside reverse transcription inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height Z-scores for 24 months were evaluated using generalized linear repeated measures models. Recovery from being underweight (WAZ<-2), stunted (HAZ<-2) and wasted (weight-for-height <-2) to Z-scores greater than -2 was also compared by arm using Kaplan-Meier survival and Cox proportional hazard modeling. RESULTS: A total of 129 children with median age of 3 years initiated therapy; 64 received LPV/r-based and 65 non nucleoside reverse transcription inhibitor-based ART (nevirapine: 36 and efavirenz: 29). The median (interquartile range) difference in growth measures between baseline and 24 months for LPV/r (n = 45) versus non nucleoside reverse transcription inhibitor-based therapy (n = 40) were as follows: WAZ, 0.47 (0.10, 1.62) versus 0.53 (0.03, 1.14) (P = 0.59) and HAZ, median 1.55 (0.78, 1.86) versus 1.19 (0.62, 1.65) (P = 0.23), respectively. ART regimen was not predictive of change in WAZ (β: -0.02, 95% confidence interval: -0.25, 0.20) or HAZ (β: 0.05, 95% confidence interval: -0.10, 0.19). The presence of confirmed virologic failure was not associated with growth. CONCLUSIONS: Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months after ART initiation, with no significant difference between those receiving LPV/r versus non nucleoside reverse transcriptase inhibitor-based ART. However, the persistence of median Z-scores below 0 underscores the need for additional strategies to improve growth outcomes in HIV+ African children

Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

OBJECTIVE: Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. DESIGN: Prospective cohort. METHODS: HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. RESULTS: Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. CONCLUSIONS: In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. TRIAL REGISTRATION: Clinicaltrials.gov NCT00993031

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.)

High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya.

INTRODUCTION: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. METHODS: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/μL and children (two to fourteen years) with CD4 > 500/μL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events. Results Overall, 972 HIV-positive adults with CD4+ ≥ 350/μL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28-42), CD4+ 608/μL (IQR, 487-788/μL) and VL 6775 copies/mL (IQR, <500-37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to follow-up). Viral suppression occurred in 778/838 (93%) and 800/972 (82%) in intention-to-treat analysis. Grade III/IV clinical/laboratory adverse events were rare: 95 occurred in 74/972 patients (7.6%). Only 8/972 adults (0.8%) switched ART from EFV to lopinavir (LPV) (n = 2 for dizziness, n = 2 for gynaecomastia, n = 4 for other reasons). Among 83 children, week 48 retention was 89% (74/83), viral suppression was 92% (65/71) and grade III/IV adverse events occurred in 4/83 (4.8%). CONCLUSIONS: Using a streamlined care model, viral suppression, retention and ART safety were high among asymptomatic East African adults and children with high CD4+ counts initiating treatment. CLINICAL TRIAL NUMBER: NCT01864603

Men's Health Study: A Cross Sectional Study of HIV among Men Who Have Sex with Men in Kisumu, Kenya

In Kisumu, Kenya a cross-sectional study was implemented to sample men who have sex with men (MSM) to determine the prevalence of Human Immunodeficiency Virus (HIV) and other sexually transmitted infections (STIs) among them and to identify demographic and behavioral factors associated with HIV infection. Due to the highly stigmatized nature of same sex activity in Kenya, a sampling technique efficient at identifying members of hard to reach populations called respondent driven sampling (RDS) was employed. The enrolled men completed a behavioral questionnaire and underwent rapid HIV testing and subsequent STI testing. Adjusting for sampling design, HIV prevalence was 11%, twice as high as the Kenyan national prevalence among men, but comparable to sexually active men in Kisumu, Kenya. Controlling for age, ethnicity and highest educational attainment, prevalent Herpes Simplex Virus 2 (HSV-2) infection, past history of genital ulcerative disease and unprotected vaginal intercourse at last sex with a woman were factors strongly associated with prevalent HIV infection

Impact of a Structural Intervention to Address Alcohol Use Among Gay Bar Patrons in San Francisco: The PACE Study.

We evaluated the impact on alcohol intake and blood alcohol concentration (BAC) of a multi-level structural intervention to increase the availability of free water, coupled with messaging on pacing alcohol intake and normative feedback of blood alcohol concentration in a convenience sample of gay bars in San Francisco. Participants (n&nbsp;=&nbsp;1,293) were recruited among exiting patrons of four gay bars (two intervention bars and two control bars). Participants were surveyed on alcohol intake and BAC was measured by breathalyzer. Prior to the intervention there were no significant differences in baseline alcohol measures between intervention and control bars. Post-intervention there were significant differences on objective and subjective measures of alcohol consumption: 30% of intervention bar participants had BAC% levels over the legal driving limit (0.08%) compared to 43% of control bar participants, p&nbsp;&lt;&nbsp;0.0001 and 78% of intervention bar participants were above the AUDIT-C cut-off for hazardous drinking compared to 87% in control bars, p&nbsp;&lt;&nbsp;0.001