Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Estimation of HIV-1 Incidence Using a Testing History-Based Method; Analysis From the Population-Based HIV Impact Assessment Survey Data in 12 African Countries.

BACKGROUND: Estimating HIV incidence is essential to monitoring progress in sub-Saharan African nations toward global epidemic control. One method for incidence estimation is to test nationally representative samples using laboratory-based incidence assays. An alternative method based on reported HIV testing history and the proportion of undiagnosed infections has recently been described. METHODS: We applied an HIV incidence estimation method which uses history of testing to nationally representative cross-sectional survey data from 12 sub-Saharan African nations with varying country-specific HIV prevalence. We compared these estimates with those derived from laboratory-based incidence assays. Participants were tested for HIV using the national rapid test algorithm and asked about prior HIV testing, date and result of their most recent test, and date of antiretroviral therapy initiation. RESULTS: The testing history-based method consistently produced results that are comparable and strongly correlated with estimates produced using a laboratory-based HIV incidence assay (ρ = 0.85). The testing history-based method produced incidence estimates that were more precise compared with the biomarker-based method. The testing history-based method identified sex-, age-, and geographic location-specific differences in incidence that were not detected using the biomarker-based method. CONCLUSIONS: The testing history-based method estimates are more precise and can produce age-specific and sex-specific incidence estimates that are informative for programmatic decisions. The method also allows for comparisons of the HIV transmission rate and other components of HIV incidence among and within countries. The testing history-based method is a useful tool for estimating and validating HIV incidence from cross-sectional survey data.

Toward elimination of mother-to-child transmission of HIV in Malawi: Findings from the Malawi Population-based HIV Impact Assessment (2015-2016).

BACKGROUND: Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. METHODS: MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). RESULTS: Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. CONCLUSIONS: MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.

A comparison of two population-based household surveys in Uganda for assessment of violence against youth.

Violence is associated with health-risk behaviors, potentially contributing to gender-related HIV incidence disparities in sub-Saharan Africa. Previous research has demonstrated that violence, gender, and HIV are linked via complex mechanisms that may be direct, such as through forced sex, or indirect, such as an inability to negotiate safe sex. Accurately estimating violence prevalence and its association with HIV is critical in monitoring programmatic efforts to reduce both violence and HIV. We compared prevalence estimates of violence in youth aged 15-24 years from two Ugandan population-based cross-sectional household surveys (Uganda Violence Against Children Survey 2015 [VACS] and Uganda Population-based HIV Impact Assessment 2016-2017 [UPHIA]), stratified by gender. UPHIA violence estimates were consistently lower than VACS estimates, including lifetime physical violence, recent intimate partner physical violence, and lifetime sexual violence, likely reflecting underestimation of violence in UPHIA. Multiple factors likely contributed to these differences, including the survey objectives, interviewer training, and questionnaire structure. VACS may be better suited to estimate distal determinants of HIV acquisition for youth (including experience of violence) than UPHIA, which is crucial for monitoring progress toward HIV epidemic control.

Opportunities for Closing the Gap in HIV Diagnosis, Treatment, and Viral Load Suppression in Children in Malawi: Results From a 2015-2016 Population-based HIV Impact Assessment Survey.

BACKGROUND: Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. METHODS: In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection. RESULTS: Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1-1.9) and 8.0% (95% CI: 5.6-10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028-149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3-41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8-95.6) were on ART and 57.9% (95% CI: 41.4-74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0-70.5) had unsuppressed VL. CONCLUSIONS: Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions.

Factors associated with unawareness of HIV-positive status in urban Ethiopia: Evidence from the Ethiopia population-based HIV impact assessment 2017-2018.

BACKGROUND: The HIV epidemic in Ethiopia is concentrated in urban areas. Ethiopia conducted a Population-based HIV Impact Assessment (EPHIA) in urban areas between October 2017 and April 2018 to measure the status of the country's response to the epidemic. METHODS: We conducted field data collection and HIV testing in randomly selected households using the national, rapid testing algorithm with laboratory confirmation of seropositive samples using a supplemental assay. In addition to self-report on HIV diagnosis and treatment, all HIV-positive participants were screened for a set of HIV antiretroviral (ARV) drugs indicative of the first- and second-line regimens. We calculated weighted frequencies and 95% confidence intervals to assess regional variation in participants' level of unawareness of their HIV-positive status (adjusted for ARV status). RESULTS: We interviewed 20,170 survey participants 15-64 years of age, of which 19,136 (95%) were tested for HIV, 614 (3.2%) tested positive, and 119 (21%) of HIV-positive persons were unaware of their HIV status. Progress towards the UNAIDS first 90 target (90% of people living with HIV would be aware of their HIV status by 2020) substantially differed by administrative region of the country. In the bivariate analysis using log binomial regression, three regions (Oromia, Addis Ababa, and Harari), male gender, and young age (15-24 years) were significantly associated with awareness of HIV positive status. In multivariate analysis, the same variables were associated with awareness of HIV-positive status. CONCLUSION: One-fifth of the HIV-positive urban population were unaware of their HIV-positive status. The number of unaware HIV-positive individuals has a different distribution than the HIV prevalence. National and regional planning and monitoring activities could address this potentially substantial source of undetected HIV infection by increasing HIV testing among young people, men and individuals who do not use condoms.

A Comprehensive Approach to Assuring Quality of Laboratory Testing in HIV Surveys: Lessons Learned From the Population-Based HIV Impact Assessment Project.

BACKGROUND: Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys. METHODS: Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results. RESULTS: Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing. CONCLUSIONS: Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.

HIV Incidence by Male Circumcision Status From the Population-Based HIV Impact Assessment Surveys-Eight Sub-Saharan African Countries, 2015-2017.

BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally representative samples. Data from the population-based HIV impact assessments were used to compare HIV incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from population-based HIV impact assessments conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2017. Incidence was measured using a recent infection testing algorithm and analyzed by self-reported MC status distinguishing between medical and nonmedical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random-effects logistic regression model using pooled survey weights. Analyses were age stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men [0.04% (95% CI: 0.00% to 0.10%) versus 0.34% (95% CI: 0.10% to 0.57%), respectively; P value = 0.01]; whereas among men 35-59 years, there was no significant incidence difference [1.36% (95% CI: 0.32% to 2.39%) versus 0.55% (95% CI: 0.14% to 0.67%), respectively; P value = 0.14]. DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa.

Screening for HIV Among Patients at Tuberculosis Clinics - Results from Population-Based HIV Impact Assessment Surveys, Malawi, Zambia, and Zimbabwe, 2015-2016.

The World Health Organization and national guidelines recommend HIV testing and counseling at tuberculosis (TB) clinics for all patients, regardless of TB diagnosis (1). Population-based HIV Impact Assessment (PHIA) survey data for 2015-2016 in Malawi, Zambia, and Zimbabwe were analyzed to assess HIV screening at TB clinics among persons who had positive HIV test results in the survey. The analysis was stratified by history of TB diagnosis* (presumptive versus confirmed†), awareness§ of HIV-positive status, antiretroviral therapy (ART)¶ status, and viral load suppression among HIV-positive adults, by history of TB clinic visit. The percentage of adults who reported having ever visited a TB clinic ranged from 4.7% to 9.7%. Among all TB clinic attendees, the percentage who reported that they had received HIV testing during a TB clinic visit ranged from 48.0% to 62.1% across the three countries. Among adults who received a positive HIV test result during PHIA and who did not receive a test for HIV at a previous TB clinic visit, 29.4% (Malawi), 21.9% (Zambia), and 16.2% (Zimbabwe) reported that they did not know their HIV status at the time of the TB clinic visit. These findings represent missed opportunities for HIV screening and linkage to HIV care. In all three countries, viral load suppression rates were significantly higher among those who reported ever visiting a TB clinic than among those who had not (p<0.001). National programs could strengthen HIV screening at TB clinics and leverage them as entry points into the HIV diagnosis and treatment cascade (i.e., testing, initiation of treatment, and viral load suppression).

Prevalence and correlates of active syphilis and HIV co-Infection among sexually active persons aged 15-59 years in Zambia: Results from the Zambia Population-based HIV Impact Assessment (ZAMPHIA) 2016.

OBJECTIVES: The main objectives of the study are to estimate HIV prevalence, active syphilis prevalence, and correlates of co-infection with HIV in Zambia, among recently sexually active individuals aged 15 to 59 years old. METHODS: We used data from the 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA), a national household survey that included biomarker testing for HIV and syphilis. Chembio DPP® Syphilis Screen and Confirm Assay was used to distinguish between active and older syphilis infections. This is the first time Chembio DPP® has been used in a national survey. Log-binominal modelling was utilized to understand the risk of acquiring HIV/active syphilis co-infection using select socio-demographic and sexual behavior variables. Multivariable analysis compared those with co-infection and those with no infection. All reported results account for the complex survey design and are weighted. RESULTS: A total of 19,114 individuals aged 15-59 years responded to the individual interview and had a valid syphilis and/or HIV test. The prevalence for those sexually active in the 12 months preceding ZAMPHIA 2016 was 3.5% and 13% for active syphilis and HIV, respectively. The prevalence of HIV/active syphilis co-infection was 1.5%. Factors associated with higher prevalence of co-infection versus no infection among females included, but were not limited to, those living in urban areas (adjusted prevalence ratio (aPR) = 3.0, 95% CI = 1.8, 4.8), those had sexual intercourse before age 15 years (aPR = 1.8, 95% CI = 1.1, 2.9), and those who had two or more sexual partners in the 12 months preceding the survey (aPR = 2.7, 95% CI = 1.6, 4.7). CONCLUSION: These findings show high prevalence for both mono-infection with HIV and syphilis, as well as co-infection with HIV/active syphilis in Zambia. There is a need for better screening and partner services, particularly among those engaging in high-risk sexual behaviors (e.g., engaging in transactional sex).

Returning HIV-1 viral load results to participant-selected health facilities in national Population-based HIV Impact Assessment (PHIA) household surveys in three sub-Saharan African Countries, 2015 to 2016.

INTRODUCTION: Logistical complexities of returning laboratory test results to participants have precluded most population-based HIV surveys conducted in sub-Saharan Africa from doing so. For HIV positive participants, this presents a missed opportunity for engagement into clinical care and improvement in health outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which measure HIV incidence and the prevalence of viral load (VL) suppression in selected African countries, are returning VL results to health facilities specified by each HIV positive participant within eight weeks of collection. We describe the performance of the specimen and data management systems used to return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. METHODS: Consenting participants underwent home-based counseling and HIV rapid testing as per national testing guidelines; all confirmed HIV positive participants had VL measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000 platform. On a bi-weekly basis, a dedicated data management team produced logs linking the VL test result with the participants' contact information and preferred health facility; project staff sent test results confidentially via project drivers, national courier systems, or electronically through an adapted short message service (SMS). Participants who provided cell phone numbers received SMS or phone call alerts regarding availability of VL results. RESULTS AND DISCUSSION: From 29,634 households across the three countries, 78,090 total participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia underwent blood draw and HIV testing. Of the 8391 total HIV positive participants identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were returned to the selected health facilities. Of the 5979 VL results returned in Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates were unavailable all 2266 returnable results reached the health facilities by 11 weeks. CONCLUSIONS: The first three PHIA surveys returned the vast majority of VL results to each HIV positive participant's preferred health facility within the eight-week target. Even in the absence of national VL monitoring systems, a system to return VL results from a population-based survey is feasible, but it requires developing laboratory and data management systems and dedicated staff. These are likely important requirements to strengthen return of results systems in routine clinical care.

Effectiveness of recall notification: community response to a nationwide recall of hot dogs and deli meats.

We examined the efficacy of recall notification and advertising in informing the public about a nationwide recall of hot dogs and deli meats. As part of an ongoing random population telephone survey, residents of seven states were interviewed. Data from the survey were weighted to account for the multistage sampling design. Overall, 307 (45%) of 633 knew about the recall. Knowledge was higher among persons older than 40 years (odds ratio = 2.1, 95% confidence interval = 1.4 to 3.3) and persons interviewed after major newspaper notices about the recall. Among those who knew about the recall, 5% believed the products were safe to eat; 23% were not sure. Seventy percent learned about the recall through television. Our findings indicate that routine recall notifications failed to reach a large portion of the population and were not well understood. Messages to the public about recalled products should clearly describe the risks of consuming the recalled product. Supplemental advertising by manufacturers can be beneficial if the risks of consuming the recalled product and recommendations to consumers are clearly described. These policies, coupled with broader distribution through the television and print media, may help increase the proportion of the persons who receive the information they need from future product recalls.

FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States.

To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.