Gabriel Chamie

Leveraging rapid community-based hiv testing campaigns for non-communicable diseases in rural uganda

Background The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish. Methods A five-day, multi-disease campaign, offering diagnostic, preventive, treatment and referral services, was performed in May 2011. Services included point-of-care screening for HIV, malaria, TB, hypertension and diabetes. Finger-prick diagnostics eliminated the need for phlebotomy. HIV-infected adults met clinic staff and peer counselors on-site; those with CD4≤100/µL underwent intensive counseling and rapid referral for antiretroviral therapy (ART). Community participation, case-finding yield, and linkage to care three months post-campaign were analyzed. Results Of 6,300 residents, 2,323/3,150 (74%) adults and 2,020/3,150 (69%) children participated. An estimated 95% and 52% of adult female and male residents participated respectively. Adult HIV prevalence was 7.8%, with 46% of HIV-infected adults newly diagnosed. Thirty-nine percent of new HIV diagnoses linked to care. In a pilot subgroup with CD4≤100, 83% linked and started ART within 10 days. Malaria was identified in 10% of children, and hypertension and diabetes in 28% and 3.5% of adults screened, respectively. Sixty-five percent of hypertensives and 23% of diabetics were new diagnoses, of which 43% and 61% linked to care, respectively. Screening identified suspected TB in 87% of HIV-infected and 19% of HIV-uninfected adults; 52% percent of HIV-uninfected TB suspects linked to care. Conclusions In an integrated campaign engaging 74% of adult residents, we identified a high burden of undiagnosed HIV, hypertension and diabetes. Improving male attendance and optimizing linkage to care require new approaches. The campaign demonstrates the feasibility of integrating hypertension, diabetes and communicable diseases into HIV initiatives.

Factors Associated with Seronegative Chronic Hepatitis C Virus Infection in HIV Infection

BACKGROUND Chronic seronegative hepatitis C virus (HCV) infection is defined as being HCV antibody (anti-HCV) negative, but HCV RNA positivity occurs in individuals infected with human immunodeficiency virus (HIV). However, associated factors are not well established because of the small number of reported cases. METHODS Multivariate logistic regression analysis of HIV-infected subjects from 4 cohorts (Tien et al., 2006; Bonacini et al., 2001; George et al., 2002; and Hall et al., 2004) determined factors associated with HCV RNA positivity in anti-HCV-negative subjects. HCV enzyme immunoassay 2.0 was used to determine anti-HCV status. RESULTS Among 1174 anti-HCV-negative, HIV-infected subjects, the prevalence of seronegative HCV infection was 3.2% (95% confidence interval [CI], 2.2%-4.3%). History of injection drug use (IDU; OR, 5.8; 95% CI, 2.7-12.8), higher alanine aminotransferase (ALT) level (OR, 2.0 per doubling; 95% CI, 1.3-3.2), and CD4 cell count <200 cells/ micro L (OR, 2.3; 95% CI, 1.1-4.8) were associated with HCV RNA positivity in anti-HCV-negative subjects. Among those with a history of IDU who had either a CD4 cell count <200 cells/ micro L or an ALT level greater than the upper limit of normal, the prevalence of seronegative HCV infection was 24% (95% CI, 13%-39%). CONCLUSIONS Detectable HCV RNA in the context of a negative HCV enzyme immunoassay 2.0 result in HIV-infected patients is low, but higher than the reported prevalence in HIV-uninfected patients. Our findings suggest that HCV RNA testing should be performed in anti-HCV-negative, HIV-infected patients, especially those with a history of IDU and either a CD4 cell count <200 cells/ micro L or an abnormal ALT level.

A hybrid mobile approach for population-wide HIV testing in rural east Africa: an observational study

Background Despite large investments in HIV testing, only 45% of HIV-infected persons in sub-Saharan Africa are estimated to know their status. Optimal methods for maximizing population-level testing remain unknown. We sought to demonstrate the effectiveness at achieving population-wide testing coverage of a hybrid mobile HIV testing approach. Methods From 2013–2014, we enumerated 168,772 adult (≥15 years) residents of 32 communities in Uganda (N=20), and Kenya (N=12) using a door-to-door census. “Stable” residence was defined as living in community for ≥6 months over the past year. In each community we performed 2-week multi-disease community health campaigns (CHC) that included HIV testing, counseling, and referral to care if HIV-infected; CHC non-participants were approached for home-based testing (HBT) over 1–2 months. We determined population HIV testing coverage, and predictors of testing via HBT (vs. CHC) and non-testing. Findings HIV testing was achieved in 89% of stable adult residents (131,307/146,906). HIV prevalence was 9.6% (13,043/136,033 stable and non-stable adults); median CD4+ T-cell count was 514 cells/μL (IQR: 355–703). Among stable adults tested, 43% (56,106/131,307) reported no prior testing. Among HIV-infected adults, 38% (4,932/13,043) were unaware of their status. Among stable CHC attendees, 99.5% (104,635/105,170) accepted HIV testing. Of stable adults tested, 80% (104,635/131,307, range: 60–93%) tested via CHCs. In multivariable analyses of stable adults, predictors of non-testing included male gender (risk ratio [RR]: 1.52, 95% CI: 1.48–1.56), single marital status (RR: 1.70, 95% CI: 1.66–1.75), Kenyan residence (RR: 1.46, 95% CI: 1.41–1.50, vs. Ugandan), and out-of-community migration for ≥1 month in past year (RR: 1.60, 95% CI: 1.53–1.68). Testing was more common among farmers (RR: 0.73, 95% CI: 0.67–0.79) and adults with primary education (RR: 0.84, 95% CI: 0.80–0.89). Interpretation High HIV testing coverage was achieved in rural Ugandan and Kenyan communities using a hybrid, mobile approach of multi-disease CHCs followed by HBT. This approach allowed for flexibility at the community and individual level in reaching testing coverage goals. Men and mobile populations remain challenges for universal testing.

Uptake of Community-Based HIV Testing during a Multi-Disease Health Campaign in Rural Uganda

Background The high burden of undiagnosed HIV in sub-Saharan Africa is a major obstacle for HIV prevention and treatment. Multi-disease, community health campaigns (CHCs) offering HIV testing are a successful approach to rapidly increase HIV testing rates and identify undiagnosed HIV. However, a greater understanding of population-level uptake is needed to maximize effectiveness of this approach. Methods After community sensitization and a census, a five-day campaign was performed in May 2012 in a rural Ugandan community. The census enumerated all residents, capturing demographics, household location, and fingerprint biometrics. The CHC included point-of-care screening for HIV, malaria, TB, hypertension and diabetes. Residents who attended vs. did not attend the CHC were compared to determine predictors of participation. Results Over 12 days, 18 census workers enumerated 6,343 residents. 501 additional residents were identified at the campaign, for a total community population of 6,844. 4,323 (63%) residents and 556 non-residents attended the campaign. HIV tests were performed in 4,795/4,879 (98.3%) participants; 1,836 (38%) reported no prior HIV testing. Of 2674 adults tested, 257 (10%) were HIV-infected; 125/257 (49%) reported newly diagnosed HIV. In unadjusted analyses, adult resident campaign non-participation was associated with male sex (62% male vs. 67% female participation, p = 0.003), younger median age (27 years in non-participants vs. 32 in participants; p<0.001), and marital status (48% single vs. 71% married/widowed/divorced participation; p<0.001). In multivariate analysis, single adults were significantly less likely to attend the campaign than non-single adults (relative risk [RR]: 0.63 [95% CI: 0.53–0.74]; p<0.001), and adults at home vs. not home during census activities were significantly more likely to attend the campaign (RR: 1.20 [95% CI: 1.13–1.28]; p<0.001). Conclusions CHCs provide a rapid approach to testing a majority of residents for HIV in rural African settings. However, complementary strategies are still needed to engage young, single adults and achieve universal testing.

Tuberculosis as Part of the Natural History of HIV Infection in Developing Countries

An enhanced, refocused research agenda is critical to reducing the burden of tuberculosis (TB) in the human immunodeficiency virus (HIV) epidemic in developing countries. TB threatens HIV-infected patients before and after initiation of antiretroviral therapy, is difficult to diagnose, is rapidly fatal when it is drug resistant, and is being spread in clinics and hospitals. Research priorities include improved and point-of-care TB diagnostics; TB treatment and prevention during HIV infection, drug-resistant TB, and childhood TB; and optimization of TB and HIV program integration. With new TB diagnostics and drugs reaching approval, research must focus on effectively deploying these advancements. Research must include evaluations of individual, household, health care, and community approaches. Studies must apply implementation science to determine how to increase and adapt effective interventions to reduce TB burden in the context of HIV infection. Investment in this research will improve the lives of persons infected with HIV and contribute to efforts to reduce the global TB burden.

Assessment of Population-Based HIV RNA Levels in a Rural East African Setting Using a Fingerprick-Based Blood Collection Method

BACKGROUND Population-based human immunodeficiency virus type 1 (HIV-1) RNA levels (viral load [VL]) are proposed metrics for antiretroviral therapy (ART) program effectiveness. We estimated population-based HIV RNA levels using a fingerprick-based approach in a rural Ugandan community implementing rapid ART scale-up. METHODS A fingerprick-based HIV RNA measurement technique was validated against standard phlebotomy. This technique was deployed during a 5-day community-wide health campaign in a 6300-person community. Assessments included rapid HIV antibody testing, VL, and CD4+ T-cell count via fingerprick. We estimated population HIV RNA levels and the prevalence of undetectable RNA, assessed predictors of VL via linear regression, and mapped RNA levels within community geographic units. RESULTS During the community-wide health campaign, 179 of 2282 adults (7.8%) and 10 of 1826 children (0.5%) tested seropositive for HIV. Fingerprick VL was determined in 174 of 189 HIV-positive persons (92%). The mean log(VL) was 3.67 log (95% confidence interval [CI], 3.50-3.83 log copies/mL), median VL was 2720 copies/mL (interquartile range, <486-38 120 copies/mL), and arithmetic mean VL was 64 064 copies/mL. Overall, 64 of 174 of individuals had undetectable RNA (37% [95% CI, 30%-44%]), 24% had VL 486-10 000; 25% had VL 10 001-100 000; and 15% had VL>100 000 copies/mL. Among participants taking ART, 83% had undetectable VL. CONCLUSIONS We developed and implemented a fingerprick VL testing method and provide the first report of population HIV RNA levels in Africa. In a rural Ugandan community experiencing ART scale-up, we found evidence of population-level ART effectiveness, but found a substantial population to be viremic, in need of ART, and at risk for transmission.

Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa

Importance Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. Objective To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Design, Setting, and Participants Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Main Outcomes and Measures Primary outcome was viral suppression (plasma HIV RNA<500 copies/mL) among all HIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART. Results Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Conclusions and Relevance Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation. Trial Registration clinicaltrials.gov Identifier: NCT01864683

Increased Morbidity in Early Childhood Among HIV-exposed Uninfected Children in Uganda is Associated with Breastfeeding Duration

Human immunodeficiency virus (HIV)-exposed uninfected children (HEU) have an increased risk of morbidity and mortality compared with HIV-unexposed uninfected children (HUU); however, prior studies have not fully accounted for the role of both breastfeeding and age on this association. In this cohort of HEU and HUU in Uganda, non-breastfeeding HEU, from 6-11 months compared with non-breastfeeding HUU had a higher risk of hospitalizations [relative risk (RR): 10.1, 95% confidence interval (CI): 3.70-27.6], severe febrile illness (RR: 3.84, 95% CI: 2.06-7.17), severe diarrhea (RR: 6.37, 95% CI: 2.32-17.4) and severe malnutrition (RR: 18.4, 95% CI: 4.68-72.0). There were no differences between morbidity outcomes between breastfeeding HEU and HUU children, aged 6-11 months. In the 12-24 month age group, the only difference in morbidity outcomes among non-breast feeding children was an increased risk of severe malnutrition for HEU. These data suggest that the increased risk of morbidity among HEU aged 6-11 years is partially explained by early cessation of breastfeeding.

High Retention in Care Among HIV-Infected Patients Entering Care With CD4 Levels >350 cells/μL Under Routine Program Conditions in Uganda

BACKGROUND In Africa, human immunodeficiency virus (HIV)-infected patients who present to care with CD4 levels >350 cells/µL (ie, current antiretroviral treatment thresholds) are often thought to be poorly retained in care, but most estimates do not account for outcomes among patients lost to follow-up. METHODS We evaluated HIV-infected adults who had made a visit in the last 2.5 years in a program in Uganda. We identified a random sample of patients lost to follow-up (9 months without a visit). Ascertainers sought patients in the community in this sample and outcomes were incorporated into revised survival estimates of mortality and retention for the clinic population using a probability weight. RESULTS Of 6473 patients, (29% male, median age 29 years, median CD4 count 550 cells/µL), 1294 (20%) became lost to follow-up over 2.5 years. Two hundred seven (16%) randomly selected lost patients were sought, and in 175 (85%) vital status was ascertained. In 19 of 175 (11%), the patient had died. Of the 156 (89%) alive, 74 (47%) were interviewed in person, and 38 of 74 (51%) reported HIV care elsewhere, whereas 36 of 74 (49%) were not in care. Application of weights derived from sampling found that at 2.5 years, retention among patients who enrolled with CD4 levels >350 cells/µL was 88.2% and mortality was 2.5%. Lower income, unemployment, and rural residence were associated with failure to be retained. CONCLUSIONS Retention in patients entering care with high CD4 counts under routine program conditions in Africa is high in a Ugandan care program and may be systematically underestimated in many other settings.

Improved employment and education outcomes in households of HIV-infected adults with high CD4 cell counts: evidence from a community health campaign in Uganda.

Background:There is limited evidence on the association between socioeconomic outcomes and CD4 counts in populations that include HIV-infected adults who have high CD4 counts or have not been diagnosed. We examined this association among adults in a rural Ugandan parish. Methods:A community health campaign offering diagnostic and treatment services for HIV and other diseases was conducted with Ministry of Health support. Data on campaign participants’ education and employment were collected and a detailed household socioeconomic survey was conducted among a subset of participants. Regression analyses were used to assess relationships between CD4 count and employment and education outcomes. Results:A total of 2323 adults (74% of the community) participated in the campaign; 179 of 2282 (7.8%) tested HIV-positive and 46% were newly diagnosed. Among HIV-infected adults not on antiretroviral therapy (ART), those with CD4 at least 500 worked 6.9 more days/month (P < 0.01; 39% more) and 2.5 more h per day (P < 0.05, 44% more) than those with CD4 less than 200. These effects were not significantly different from the effects for those with CD4 350–499. Children aged 6–11 years in households of adults with CD4 at least 350 did not have significantly different school enrollment rates than children in households of adults with CD4 less than 350, but differences were larger among children aged 12–18 years. Conclusion:Outcomes of HIV-infected adults with CD4 at least 350 were better than those of adults with CD4 less than 200 and resembled those of HIV-uninfected adults. The results suggest that early ART initiation may generate economic benefits by preventing a decline in socioeconomic status, but further research is needed to determine the CD4 threshold at which these benefits would be largest.