Synthetic Controls for Implementation Science: Opportunities for HIV Program Evaluation Using Routinely Collected Data.

PURPOSE OF REVIEW: HIV service delivery programs are some of the largest funded public health programs in the world. Timely, efficient evaluation of these programs can be enhanced with methodologies designed to estimate the effects of policy. We propose using the synthetic control method (SCM) as an implementation science tool to evaluate these HIV programs. RECENT FINDINGS: SCM, introduced in econometrics, shows increasing utility across fields. Key benefits of this methodology over traditional design-based approaches for evaluation stem from directly approximating pre-intervention trends by weighting of candidate non-intervention units. We demonstrate SCM to evaluate the effectiveness of a public health intervention targeting HIV health facilities with high numbers of recent infections on trends in pre-exposure prophylaxis (PrEP) enrollment. This test case demonstrates SCM's feasibility for effectiveness evaluations of site-level HIV interventions. HIV programs collecting longitudinal, routine service delivery data for many facilities, with only some receiving a time-specified intervention, are well-suited for evaluation using SCM.

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.

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.

Correcting for selection bias in HIV prevalence estimates: an application of sample selection models using data from population-based HIV surveys in seven sub-Saharan African countries.

INTRODUCTION: Population-based biomarker surveys are the gold standard for estimating HIV prevalence but are susceptible to substantial non-participation (up to 30%). Analytical missing data methods, including inverse-probability weighting (IPW) and multiple imputation (MI), are biased when data are missing-not-at-random, for example when people living with HIV more frequently decline participation. Heckman-type selection models can, under certain assumptions, recover unbiased prevalence estimates in such scenarios. METHODS: We pooled data from 142,706 participants aged 15-49 years from nationally representative cross-sectional Population-based HIV Impact Assessments in seven countries in sub-Saharan Africa, conducted between 2015 and 2018 in Tanzania, Uganda, Malawi, Zambia, Zimbabwe, Lesotho and Eswatini. We compared sex-stratified HIV prevalence estimates from unadjusted, IPW, MI and selection models, controlling for household and individual-level predictors of non-participation, and assessed the sensitivity of selection models to the copula function specifying the correlation between study participation and HIV status. RESULTS: In total, 84.1% of participants provided a blood sample to determine HIV serostatus (range: 76% in Malawi to 95% in Uganda). HIV prevalence estimates from selection models diverged from IPW and MI models by up to 5% in Lesotho, without substantial precision loss. In Tanzania, the IPW model yielded lower HIV prevalence estimates among males than the best-fitting copula selection model (3.8% vs. 7.9%). CONCLUSIONS: We demonstrate how HIV prevalence estimates from selection models can differ from those obtained under missing-at-random assumptions. Further benefits include exploration of plausible relationships between participation and outcome. While selection models require additional assumptions and careful specification, they are an important tool for triangulating prevalence estimates in surveys with substantial missing data due to non-participation.

Prevalence of and factors associated with late diagnosis of HIV in Malawi, Zambia, and Zimbabwe: Results from population-based nationally representative surveys.

INTRODUCTION: Late diagnosis of HIV (LD) increases the risk of morbidity, mortality, and HIV transmission. We used nationally representative data from population-based HIV impact assessment (PHIA) surveys in Malawi, Zambia, and Zimbabwe (2015-2016) to characterize adults at risk of LD and to examine associations between LD and presumed HIV transmission to cohabiting sexual partners. METHODS: We estimated the prevalence of LD, defined as CD4 count <350 cells/µL, among adults newly diagnosed with HIV during the surveys and odds ratios for associated factors. We linked newly diagnosed adults (index cases) to their household sexual partners and calculated adjusted odds ratios for associations between LD of the index case, viral load of the index case, and duration of HIV exposure in the relationship, and the HIV status of the household sexual partner. RESULTS: Of 1,804 adults who were newly diagnosed with HIV in the surveys, 49% (882) were diagnosed late. LD was associated with male sex, older age, and almost five times the odds of having an HIV-positive household sexual partner (adjusted odds ratio [aOR], 4.65 [95% confidence interval: 2.56-8.45]). Longer duration of HIV exposure in a relationship and higher viral load of the index case were both independently associated with higher odds of having HIV-positive household sexual partners. Individuals with HIV exposure of more than 5 years had more than three times (aOR 3.42 [95% CI: 1.63-7.18]) higher odds of being HIV positive than those with less than 2 years HIV exposure. The odds of being HIV positive were increased in individuals who were in a relationship with an index case with a viral load of 400-3499 copies/mL (aOR 4.06 [95% CI 0.45-36.46]), 3,500-9,999 copies/mL (aOR 11.32 [95% CI: 4.08-31.39]), 10,000-49,999 copies/mL (aOR 17.07 [95% CI: 9.18-31.72]), and ≥50,000 copies/mL (aOR 28.41 [95% CI: 12.18-66.28]) compared to individuals who were in a relationship with an index case with a viral load of <400 copies/mL. CONCLUSIONS: LD remains a challenge in Southern Africa and is strongly associated with presumed HIV transmission to household sexual partners. Our study underscores the need for earlier HIV diagnosis, particularly among men and older adults, and the importance of index testing.

HIV incidence, viremia, and the national response in Eswatini: Two sequential population-based surveys.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country.

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.

Progress Toward the 90-90-90 HIV Targets in Zimbabwe and Identifying Those Left Behind.

OBJECTIVE: We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. DESIGN: We conducted a cross-sectional household survey. METHODS: Consenting adults and children in the household were eligible to participate in Zimbabwe Population-based HIV Impact Assessment (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. Viral load suppression (VLS) was defined as HIV RNA <1000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15-64 years. RESULTS: We enrolled 11,098 men and 14,033 women aged 15-64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9 to 78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1 to 89.7) were receiving antiretroviral therapy (ART), and of these people, 85.3% (95% CI: 83.4 to 87.1) had VLS. Male sex age 15-34 years and having 1 or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS. CONCLUSIONS: Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged <35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets.

Population-Based HIV Impact Assessments Survey Methods, Response, and Quality in Zimbabwe, Malawi, and Zambia.

BACKGROUND: The population-based HIV impact assessment (population-based HIV impact assessments) surveys are among the first to estimate national adult HIV incidence, subnational prevalence of viral load suppression, and pediatric HIV prevalence. We summarize the survey methods implemented in Zimbabwe, Malawi, and Zambia, as well as response rates and quality metrics. METHODS: Each cross-sectional, household-based survey used a 2-stage cluster design. Survey preparations included sample design, questionnaire development, tablet programming for informed consent and data collection, community mobilization, establishing a network of satellite laboratories, and fieldworker training. Interviewers collected demographic, behavioral, and clinical information using tablets. Blood was collected for home-based HIV testing and counseling (HBTC) and point-of-care CD4+ T-cell enumeration with results immediately returned. HIV-positive blood samples underwent laboratory-based confirmatory testing, HIV incidence testing, RNA polymerase chain reaction (viral load), DNA polymerase chain reaction (early infant diagnosis), and serum antiretroviral drug detection. Data were weighted for survey design, and chi square automatic interaction detection-based methods were used to adjust for nonresponse. RESULTS: Each survey recruited a nationally representative, household-based sample of children and adults over a 6-10-month period in 2015 and 2016. Most (84%-90%) of the 12,000-14,000 eligible households in each country participated in the survey, with 77%-81% of eligible adults completing an interview and providing blood for HIV testing. Among eligible children, 59%-73% completed HIV testing. Across the 3 surveys, 97.8% of interview data were complete and had no errors. CONCLUSION: Conducting a national population-based HIV impact assessment with immediate return of HIV and other point-of-care test results was feasible, and data quality was high.

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.

Data Architecture to Support Real-Time Data Analytics for the Population-Based HIV Impact Assessments.

BACKGROUND AND SETTING: Electronic data capture facilitates timely use of data. Population-based HIV impact assessments (PHIAs) were led by host governments, with funding from the President's Emergency Plan for AIDS Relief, technical assistance from the Centers for Disease Control, and implementation support from ICAP at Columbia University. We described data architectures, code-based processes, and resulting data volume and quality for 14 national PHIA surveys with concurrent timelines and varied country-level data governance (2015-2020). METHODS: PHIA project data were collected through tablets, point-of-care and laboratory testing instruments, and inventory management systems, using open-source software, vendor solutions, and custom-built software. Data were securely uploaded to the PHIA data warehouse daily or weekly and then used to populate survey-monitoring dashboards and return timely laboratory-based test results on an ongoing basis. Automated data processing allowed timely reporting of survey results. RESULTS: Fourteen data architectures were successfully established, and data from more than 450,000 participants in 30,000 files across 13 countries with completed PHIAs, and blood draws producing approximately 6000 aliquots each week per country, were securely collected, transmitted, and processed by 17 full-time equivalent staff. More than 25,600 viral load results were returned to clinics of participants' choice. Data cleaning was not needed for 98.5% of household and 99.2% of individual questionnaires. CONCLUSION: The PHIA data architecture permitted secure, simultaneous collection and transmission of high-quality interview and biomarker data across multiple countries, quick turnaround time of laboratory-based biomarker results, and rapid dissemination of survey outcomes to guide President's Emergency Plan for AIDS Relief epidemic control.

Improving Sampling Efficiency for Determining Pediatric HIV Prevalence in National Surveys: Evidence From 8 Sub-Saharan African Countries.

BACKGROUND: Measurement of mother-to-child HIV transmission through population-based surveys requires large sample sizes because of low HIV prevalence among children. We estimate potential improvements in sampling efficiency resulting from a targeted sample design. SETTING: Eight countries in sub-Saharan Africa with completed Population-based HIV Impact Assessment (PHIA) surveys as of 2017. METHODS: The PHIA surveys used a geographically stratified 2-stage sample design with households sampled from randomly selected census enumeration areas. Children (0-14 years of age) were eligible for HIV testing within a random subsample of households (usually 50%). Estimates of child HIV prevalence in each country were calculated using jackknife replicate weights. We compared sample sizes and precision achieved using this design with a 2-phase disproportionate sample design applied to strata defined by maternal HIV status and mortality. RESULTS: HIV prevalence among children ranged from 0.4% (95% confidence interval: 0.2 to 0.6) in Tanzania to 2.8% (95% confidence interval: 2.2 to 3.4) in Eswatini with achieved relative standard errors between 11% and 21%. The expected precision improved in the targeted design in all countries included in the analysis, with proportionate reductions in mean squared error ranging from 27% in Eswatini to 61% in Tanzania, assuming an equal sample size. CONCLUSIONS: Population-based surveys of adult HIV prevalence that also measure child HIV prevalence should consider targeted sampling of children to reduce required sample size, increase precision, and increase the number of positive children tested. The findings from the PHIA surveys can be used as baseline data for informing future sample designs.

HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates.

BACKGROUND: HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified. SETTING: We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates. METHODS: HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history. RESULTS: Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%-30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995). CONCLUSIONS: Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.

Successful Use of Near Point-of-Care Early Infant Diagnosis in NAMPHIA to Improve Turnaround Times in a National Household Survey.

BACKGROUND: In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants <18 months without a prior diagnosis. For the Namibia population-based HIV impact assessment (NAMPHIA), the GeneXpert platform was assessed for the feasibility of near POC EID testing compared with the standard Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) platform. Quality assurance measures and turnaround time were compared to improve EID results reporting. METHODS: NAMPHIA participants were screened for HIV exposure using Determine HIV-1/2 rapid test; samples reactive on Determine received EID testing on the GeneXpert instrument and Xpert HIV-1 Qual assay using whole blood. Results were confirmed at the Namibia Institute of Pathology using dried blood spots on the Roche CAP/CTM platform per national guidelines. RESULTS: Of the 762 screened infants, 61 (8.0%) were Determine-reactive and considered HIV-exposed. Of the 61 exposed infants, 2 were found to be HIV-infected whereas 59 were negative on both GeneXpert and Roche platforms, achieving 100% concordance. Average turnaround time was 3.4 days for the Xpert HIV-1 Qual assay, and average time from collection to testing was 1.0 days for GeneXpert compared with 10.7 days for Roche. No samples failed using GeneXpert whereas 1 sample failed using Roche and was repeated. CONCLUSION: Quality POC EID testing is feasible in a national survey through extensive training and external quality assurance measures. The use of decentralized POC EID for national testing would provide rapid diagnosis and improve TATs which may prevent loss to follow-up, ensure linkage to care, and improve clinical outcomes for infants.

Population Viral Load, Viremia, and Recent HIV-1 Infections: Findings From Population-Based HIV Impact Assessments (PHIAs) in Zimbabwe, Malawi, and Zambia.

BACKGROUND: HIV population viral load (PVL) can reflect antiretroviral therapy program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015-16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community. METHODS: We used limiting-antigen avidity enzyme immunoassay, viral load suppression (VLS) (HIV RNA <1000 copies/mL), and antiretrovirals in the blood to identify recent HIV-1 cases. RESULTS: Among 1510 enumeration areas (EAs) across the 3 surveys, 52,036 adults aged 15-59 years resided in 1363 (90.3%) EAs with at least one HIV-positive adult consenting to interview and blood draw and whose VL was tested. Mean HIV prevalence across these EAs was 13.1% [95% confidence intervals (CI) 12.7 to 13.5]. Mean VLS prevalence across these EAs was 58.7% (95% CI: 57.3 to 60.0). In multivariable analysis, PVL was associated with a recent HIV-1 case in that EA (adjusted odds ratio: 1.4, 95% CI: 1.2 to 1.6, P = 0.001). VLS prevalence was inversely correlated with recent infections (adjusted odds ratio: 0.3, 95% CI: 0.1 to 0.6, P = 0.004). The 90-90-90 indicators, namely, the prevalence of HIV diagnosis, antiretroviral therapy coverage, and VLS at the EA level, were inversely correlated with HIV recency at the EA level. CONCLUSIONS: We found a strong association between PVL and VLS prevalence and recent HIV-1 infection at the EA level across 3 southern African countries with generalized HIV epidemics. These results suggest that population-based measures of VLS in communities may serve as a proxy for epidemic control.

Evaluating Nonresponse Weighting Adjustment for the Population-Based HIV Impact Assessment Surveys on Incorporating Survey Outcomes.

BACKGROUND: The nonresponse weighting adjustment of the Population-based HIV Impact Assessment (PHIA) surveys uses the weighting class method in combination with a tree analysis to identify predictors significant to response propensity. Variable selection for this type of nonresponse adjustment identifies auxiliary variables correlated with response propensity alone and produces 1 set of weights applicable for all analyses of the survey data. An alternative approach identifies auxiliary variables correlated to both the response probability and selected key outcome variables. This approach may identify a different set of variables for the nonresponse adjustments and may produce more efficient estimates for the key outcome variables. SETTING: The PHIA surveys from 2016 to 2017. METHODS: Weighting class, joint-classification, and two-step modeling. RESULTS: There was little difference among estimates produced by the alternative weighting methods and the PHIA estimates. The joint-classification method produced more efficient estimates (ie, smaller design effects) compared with the PHIA method, while the two-step method was inconclusive. CONCLUSIONS: The efficiency of the estimates produced by the PHIA weighting method closely resembles those specifically targeted at key survey outcomes and serves well as a multipurpose weight.

Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

INTRODUCTION: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. METHODS: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. RESULTS: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. CONCLUSIONS: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence.

Comparison of HIV Incidence in the Zimbabwe Population-Based HIV Impact Assessment Survey (2015-2016) with Modeled Estimates: Progress Toward Epidemic Control.

Between October 2015 and August 2016, Zimbabwe conducted the Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA) cross-sectional survey to determine progress toward epidemic control. Of 25,131 eligible adults aged 15-64 years, 20,577 (81.8%) consented to face-to-face questionnaire and biomarker testing in this nationally representative household survey. Home-based rapid HIV testing was performed using Determine, First Response, and STAT-PAK as the tiebreaker. HIV-positive tests were confirmed in a laboratory using Geenius HIV-1/2; viral load (VL) was measured using Roche TaqMan and BioMerieux NucliSENS. Recency of infection was tested using Sedia HIV-1 Limiting Antigen (LAg)-Avidity. Presence of antiretroviral (ARV) drugs was detected using high performance liquid chromatography/mass spectrometry (HPLC/MS). The recent infection testing algorithm included LAg-avidity enzyme immunoassay [normalized optical density (ODn ≤1.5), VL ≥1,000 copies/mL, and absence of ARV drugs]. Weighted annual HIV incidence was compared with United Nations Joint Programme on HIV/AIDS (UNAIDS) Spectrum models estimates. Overall, 26 of 2,901 HIV-seropositive individuals had a recent infection (men, 8; women, 18). Overall weighted annual incidence among persons aged 15-64 years was 0.42% [95% confidence interval (CI): 0.25-0.59] and was 0.44% (95% CI: 0.25-0.62) for those aged 15-49 years, similar to 2016 Spectrum model estimate (0.54%, 95% CI: 0.49-0.66) for this age group. Among persons aged 15-49 years, HIV prevalence was 13.35% (95% CI: 12.71-14.02), estimated HIV-positive individuals were 968,951 (95% CI: 911,473-1,026,430), of these, 41,911 (95% CI: 37,412-44,787) were annual-new infections, and this was similar to 2016 Spectrum estimates. The observed HIV incidence in ZIMPHIA 2015-2016 validated the 2016 Spectrum estimates and Zimbabwe's progress toward epidemic control.

Survival and HIV-Free Survival Among Children Aged ≤3 Years - Eight Sub-Saharan African Countries, 2015-2017.

Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)§ survey data, pooled from eight sub-Saharan African countries¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Determinants of alcohol use among people living with HIV initiating isoniazid preventive therapy in Ethiopia.

BACKGROUND: Hepatotoxicity, an adverse effect of isoniazid preventative therapy (IPT), is exacerbated by alcohol consumption. Although the WHO recommends IPT for people living with HIV (PLHIV), it is contraindicated in regular alcohol users. The objective of this study was to identify the prevalence and determinants of alcohol use among PLHIV initiating IPT in Ethiopia. METHODS: Baseline data (July 2013-May 2015) from 316 participants in the Enhance Initiation and Retention in IPT Care for HIV (ENRICH) study were used to assess the prevalence of alcohol use. Multinomial logistic regression was used to identify determinants of non-hazardous and hazardous alcohol use, compared to no alcohol use. RESULTS: Overall, 41.8% of participants reported alcohol use, of which 45.5% reported hazardous use. Compared to non-alcohol users, hazardous users were younger (adjusted odds ratio [AOR]: 1.06; 95% confidence interval [95% CI]: 1.02, 1.11), more likely to be male (AOR: 6.40; 95% CI: 3.17, 12.93), Orthodox (AOR: 3.96; 95% CI: 1.74, 9.00), have larger support networks (AOR: 3.82; 95% CI: 1.61, 9.06), and report greater amount (AOR: 14.80; 95% CI: 5.76, 38.02) and frequency (AOR: 5.91; 95% CI: 2.75, 12.67) of khat use. CONCLUSIONS: Alcohol use was prevalent in this population, and current WHO guidelines would exclude a substantial proportion of the population from receiving IPT. PLHIV in this region would benefit from routine screening for alcohol and khat use, and from substance use education and counseling while receiving IPT until it can be determined whether alcohol users can safely receive IPT.