Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial

Background HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its eff ect on HIV risk is uncertain and methods to improve linkage to care have not been studied. Methods We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data offi cer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). Findings We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], diff erence –0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a signifi cant eff ect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96). Interpretation Abbreviated HIV counselling and testing did not adversely aff ect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might aff ect secondary HIV transmission and improve treatment outcomes

Potential for false positive HIV test results with the serial rapid HIV testing algorithm

Background: Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Results: Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Conclusion: Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals

Validation of World Health Organisation HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda

IntroductionThe WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3).ObjectiveTo validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda.ResultsData was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2.ConclusionThe WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda

Reviewing progress: 7 Year Trends in Characteristics of Adults and Children Enrolled at HIV Care and Treatment Clinics in the United Republic of Tanzania.

To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (>=15 years) and children (<15 years) enrolled from January 2005 to December 2011 at 44 HIV clinics in 3 regions of mainland Tanzania (Kagera, Kigoma, Pwani) and Zanzibar. Comparative statistics for trends in characteristics of patients enrolled in 2005--2007, 2008--2009 and 2010--2011 were examined. Overall 62,801 HIV+ patients were enrolled: 58,102(92.5%) adults, (66.5% female); 4,699(7.5%) children.Among adults, pregnant women enrolment increased: 6.8%, 2005--2007; 12.1%, 2008--2009; 17.2%, 2010--2011; as did entry into care from prevention of mother-to-child HIV transmission (PMTCT) programs: 6.6%, 2005--2007; 9.5%, 2008--2009; 12.6%, 2010--2011. WHO stage IV at enrolment declined: 27.1%, 2005--2007; 20.2%, 2008--2009; 11.1% 2010--2011. Of the 42.5% and 29.5% with CD4+ data at enrolment and ART initiation respectively, median CD4+ count increased: 210cells/muL, 2005--2007; 262cells/muL, 2008--2009; 266cells/muL 2010--2011; but median CD4+ at ART initiation did not change (148cells/muL overall). Stavudine initiation declined: 84.9%, 2005--2007; 43.1%, 2008--2009; 19.7%, 2010--2011.Among children, median age (years) at enrolment decreased from 6.1(IQR:2.7-10.0) in 2005--2007 to 4.8(IQR:1.9-8.6) in 2008--2009, and 4.1(IQR:1.5-8.1) in 2010--2011 and children <24 months increased from 18.5% to 26.1% and 31.5% respectively. Entry from PMTCT was 7.0%, 2005--2007; 10.7%, 2008--2009; 15.0%, 2010--2011. WHO stage IV at enrolment declined from 22.9%, 2005--2007, to 18.3%, 2008--2009 to 13.9%, 2010--2011. Proportion initiating stavudine was 39.8% 2005--2007; 39.5%, 2008--2009; 26.1%, 2010--2011. Median age at ART initiation also declined significantly. Over time, the proportion of pregnant women and of adults and children enrolled from PMTCT programs increased. There was a decline in adults and children with advanced HIV disease at enrolment and initiation of stavudine. Pediatric age at enrolment and ART initiation declined. Results suggest HIV program maturation from an emergency response

Missed Opportunities for HIV Testing and Late-Stage Diagnosis among HIV-Infected Patients in Uganda

BACKGROUND: Late diagnosis of HIV infection is a major challenge to the scale-up of HIV prevention and treatment. In 2005 Uganda adopted provider-initiated HIV testing in the health care setting to ensure earlier HIV diagnosis and linkage to care. We provided HIV testing to patients at Mulago hospital in Uganda, and performed CD4 tests to assess disease stage at diagnosis. METHODS: Patients who had never tested for HIV or tested negative over one year prior to recruitment were enrolled between May 2008 and March 2010. Participants who tested HIV positive had a blood draw for CD4. Late HIV diagnosis was defined as CD4≤250 cells/mm. Predictors of late HIV diagnosis were analyzed using multi-variable logistic regression. RESULTS: Of 1966 participants, 616 (31.3%) were HIV infected; 47.6% of these (291) had CD4 counts ≤250. Overall, 66.7% (408) of the HIV infected participants had never received care in a medical clinic. Receiving care in a non-medical setting (home, traditional healer and drug stores) had a threefold increase in the odds of late diagnosis (OR = 3.2; 95%CI: 2.1-4.9) compared to receiving no health care. CONCLUSIONS: Late HIV diagnosis remains prevalent five years after introducing provider-initiated HIV testing in Uganda. Many individuals diagnosed with advanced HIV did not have prior exposure to medical clinics and could not have benefitted from the expansion of provider initiated HIV testing within health facilities. In addition to provider-initiated testing, approaches that reach individuals using non-hospital based encounters should be expanded to ensure early HIV diagnosis

Alert, but not alarmed - a comment on "Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives (Kosack et al. 2017)".

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To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status.

INTRODUCTION: In accordance with global testing and treatment targets, many countries are seeking ways to reach the "90-90-90" goals, starting with diagnosing 90% of all people with HIV. Quality HIV testing services are needed to enable people with HIV to be diagnosed and linked to treatment as early as possible. It is essential that opportunities to reach people with undiagnosed HIV are not missed, diagnoses are correct and HIV-negative individuals are not inadvertently initiated on life-long treatment. We conducted this systematic review to assess the magnitude of misdiagnosis and to describe poor HIV testing practices using rapid diagnostic tests. METHODS: We systematically searched peer-reviewed articles, abstracts and grey literature published from 1 January 1990 to 19 April 2017. Studies were included if they used at least two rapid diagnostic tests and reported on HIV misdiagnosis, factors related to potential misdiagnosis or described quality issues and errors related to HIV testing. RESULTS: Sixty-four studies were included in this review. A small proportion of false positive (median 3.1%, interquartile range (IQR): 0.4-5.2%) and false negative (median: 0.4%, IQR: 0-3.9%) diagnoses were identified. Suboptimal testing strategies were the most common factor in studies reporting misdiagnoses, particularly false positive diagnoses due to using a "tiebreaker" test to resolve discrepant test results. A substantial proportion of false negative diagnoses were related to retesting among people on antiretroviral therapy. Conclusions HIV testing errors and poor practices, particularly those resulting in false positive or false negative diagnoses, do occur but are preventable. Efforts to accelerate HIV diagnosis and linkage to treatment should be complemented by efforts to improve the quality of HIV testing services and strengthen the quality management systems, particularly the use of validated testing algorithms and strategies, retesting people diagnosed with HIV before initiating treatment and providing clear messages to people with HIV on treatment on the risk of a "false negative" test result

A novel community health worker tool outperforms WHO clinical staging for assessment of antiretroviral therapy eligibility in a resource-limited setting.

The accuracy of a novel community health worker antiretroviral therapy eligibility assessment tool was examined in community members in Blantyre, Malawi. Nurses independently performed World Health Organization (WHO) staging and CD4 counts. One hundred ten (55.6%) of 198 HIV-positive participants had a CD4 count of <350 cells per cubic millimeter. The community health worker tool significantly outperformed WHO clinical staging in identifying CD4 count of <350 cells per cubic millimeter in terms of sensitivity (41% vs. 19%), positive predictive value (75% vs. 68%), negative predictive values (53% vs. 47%), and area under the receiver-operator curve (0.62 vs. 0.54; P = 0.017). Reliance on WHO staging is likely to result in missed and delayed antiretroviral therapy initiation