BACKGROUND: Despite widespread HIV testing in sub-Saharan Africa, regular testing among at-risk populations is crucial for effective prevention. However, reports increasingly indicate retesting among people living with HIV (PLHIV), a group that would not require additional testing since they would already have received a confirmed diagnosis. We describe the demographic characteristics of PLHIV retesters in Lesotho, report the average number of HIV tests post-diagnosis among PLHIV, and share motivations for retesting. METHODS: In August 2022, a nationally representative cohort in Lesotho participated in a cell phone survey about their HIV status and testing history. Study participants were recruited from a face-to-face survey conducted in 2020, Lesotho Population Based HIV Impact Assessment survey. RESULTS: Of the 1523 participants called, 1111 participants responded (72.9%) and 266 reported living with HIV. We found 18.8% of people living with HIV (PLHIV) reported retesting at least once for HIV, and 58% of PLHIV who reported retesting were likely or very likely to retest for HIV in the coming year. The main reason PLHIV reported retesting was because a health care worker offered the test (61.7%) followed by self-initiated testing to confirm their status (29.1%). Among male PLHIV who had a history of retesting, 92.0% were very likely or likely to retest, compared to only 30.6% of female PLHIV. CONCLUSION: We found almost a fifth of PLHIV in Lesotho reported a history of retesting for HIV, and 58% of PLHIV were likely or very likely to retest for HIV in the coming year. Educating providers and men living with HIV could reduce retesting among PLHIV.

Introduction The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a target of ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) to have viral load suppression (VLS). We examined factors associated with nonsuppressed viral Load (NVL).Methods We included PLHIV receiving ART aged 15–59 years from Eswatini, Lesotho, Malawi, Zambia, and Zimbabwe. Blood samples from PLHIV were analyzed for HIV RNA and recent exposure to antiretroviral drugs (ARVs). Outcomes were 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 receiving second-line ART. We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART.Results The prevalence of NVL was 11.2%: 8.2% experienced VF, and 3.0% interrupted ART. Younger age, male gender, 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 gender, shorter ART duration, higher CD4 count, and alcohol use were associated with higher odds for interrupted ART and lower odds for VF. 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 UNAIDS VLS targets for adults. Treatment support for people initiating ART with asymptomatic HIV infection, scale-up of viral load monitoring, and optimized ART regimens may further reduce NVL prevalence.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding: This research has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of grant number U2GGH001226. ADH was supported by a Swiss National Science Foundation (SNF) Early Postdoc Mobility Fellowship (grant number: P2BEP3_178602). Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Eswatini Scientific and Ethics Committee, the National Health Science Research Committee Malawi, the National Health Research Ethics Committee Lesotho, the National Health Research Ethics Committee Lesotho, the Tropical Diseases Research Centre Ethics Review Committee, Zambia, the Medical Research Council of Zimbabwe, and the Institutional Review Boards at the Centers for Disease Control and Prevention (CDC; Atlanta, GA) and Columbia University Medical Center (New York, NY) approved the PHIA surveys.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesPublic datasets for Eswatini, Malawi, and Zambia are available. Public datasets for Lesotho and Zimbabwe will be made available soon. For more information see: https://phia-data.icap.columbia.edu/ https://phia-data.icap.columbia.edu/

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/mm(3) (interquartile range [IQR], 307 to 654) and 811 cells/mm(3) (IQR, 647 to 1,013), respectively (P < 0.0001). Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm(3)) than those with undetectable ARVs (385.5 cells/mm(3)). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm(3), 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. 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/mm(3)) 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.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Fares-Gusmao Rafaelle, Jiang Zhen, Subramaniam Sakthivel, Visser Bryan J, Scott Alysia, Ishida Yuji, Saito Takeshi, Baylis Sally A, McGivern David R, . Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2022 157105325

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.

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.

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.

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.

OBJECTIVE: We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) 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 ZIMPHIA (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. VLS was defined as HIV RNA <1,000 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]: 74.9-78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1-89.7) were receiving ART, and of these people, 85.3% (95% CI: 83.4-87.1) had VLS. Male sex age 15-34 years and having one 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.

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.

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.

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.

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.

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.

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.

BACKGROUND: HIV population viral load (PVL) can reflect antiretroviral therapy (ART) 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 (LAg) Avidity enzyme immunoassay (EIA), VLS (HIV RNA <1000 copies/mL), and ARVs in the blood to identify recent HIV-1 cases. RESULTS: Among 1,510 EAs across the three surveys, 52,036 adults aged 15-59 years resided in 1,363 (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] 12.7-13.5). Mean VLS prevalence across these EAs was 58.7% (95% CI 57.3-60.0).In multivariable analysis, PVL was associated with a recent HIV-1 case in that EA (adjusted odds ratio [AOR]: 1.4, 95% CI 1.2-1.6, p=0.001). VLS prevalence was inversely correlated with recent infections (AOR: 0.3, 95% CI 0.1-0.6, p=0.004). The 90-90-90 indicators, namely, the prevalence of HIV diagnosis, ART coverage, and VLS at the EA level, were inversely correlated with HIV recency at the EA level. CONCLUSION: We found a strong association between PVL and VLS prevalence and recent HIV-1 infection at the EA level across three 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.

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.

BACKGROUND: Zimbabwe conducted a Population-Based HIV Impact Assessment (ZIMPHIA) cross-sectional survey, October 2015 and August 2016 to determine progress toward epidemic control. METHODS: Of 25,131 eligible adults 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 tie-breaker. 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-Avidity (LAg). Presence of antiretroviral (ARV) drugs was detected using HPLC/MS. The recent infection testing algorithm (RITA) included LAg-Avidity Enzyme-immuno-assay (EIA (normalised-optical density (ODn<=1.5), viral load>/=1000 copies/mL, and absence of antiretroviral drugs. Weighted annual HIV incidence was compared to UNAIDS Spectrum models estimates. RESULTS: Overall, 26 of 2,901 HIV-seropositive individuals had a recent infection (men, 8; women, 18). Overall weighted annual incidence among persons 15-64 years was 0.42% (95% confidence interval [CI]: 0.25-0.59) and 0.44% (95% CI: 0.25-0.62) for 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. CONCLUSION: The observed HIV incidence in ZIMPHIA 2015/16 validated the 2016 Spectrum estimates and Zimbabwe's progress toward epidemic control.

Treatment of malaria during pregnancy requires balancing the need for radical cure while avoiding teratogenic exposure. In The Lancet Infectious Diseases, Makoto Saito and colleagues report the results of a systematic review and meta-analysis that used individual patient data on antimalarial efficacy and tolerability in pregnancy.1 This impressive undertaking comprises nearly all published evidence and clearly highlights the superiority of artemisinin-based combination therapy (ACT) over quinine monotherapy, building on previous studies that focused on ACT safety in the second and third trimesters.2

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(dagger) (2). Nationally representative Population-based HIV Impact Assessment (PHIA)( section sign) survey data, pooled from eight sub-Saharan African countries( paragraph sign) 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.

Reliable and accurate laboratory assays to detect recent HIV-1 infection have potential as simple and practical methods of estimating HIV-1 incidence in cross-sectional surveys. This study describes validation of the limiting-antigen (LAg) Avidity enzyme immunoassay (EIA) in a cross-sectional national survey, conducted in Swaziland, comparing it to prospective follow up incidence. As part of the Swaziland HIV-1 Incidence Measurement Survey (SHIMS), 18,172 individuals underwent counselling and HIV rapid testing in a household-based, population survey conducted from December 2010 to June 2011. Plasma samples from HIV-positive persons were classified as recent infections using an incidence testing algorithm with LAg-Avidity EIA (ODn 1.5) followed by viral load (VL >/=1,000 copies/mL). All HIV-seronegative samples were tested for acute HIV-1 infection by nucleic acid amplification test (NAAT) pooling. HIV-seronegative individuals who consented to follow-up, were retested approximately 6 months later to detect observed HIV-1 seroconversion. HIV-1 incidence estimates based on LAg+VL and NAAT were calculated using assay-specific parameters and were compared with prospective incidence estimate. A total of 5,803 (31.9%) of 18,172 survey participants tested HIV-seropositive; of these 5683 (97.9%) were further tested with LAg+VL algorithm. The weighted annualized incidence from the longitudinal cohort study was 2.4% [95% CI 2.0, 2.7]. Based on cross-sectional testing of HIV-positives with LAg+VL algorithm, overall weighted annualized HIV-1 incidence was 2.5% [2.0, 3.0], while NAAT-based incidence was of 2.6%. In addition, LAg-based incidence in men (1.8%; 1.2-2.5) and women (3.2%; 2.4-3.9) were similar to estimates based on observed incidence (men=1.7%, women=3.1%). Changes in HIV-1 incidence with age in men and women further validate plausibility of the algorithm. These results demonstrate that the LAg EIA, in a serial algorithm with VL, is a cost-effective tool to estimate HIV-1 incidence in cross-sectional surveys.

BACKGROUND: Remarkable success in the prevention and treatment of pediatric HIV infection has been achieved in the past decade. Large differences remain between the estimated number of children living with HIV (CLHIV) and those identified through national HIV programs. We evaluated the number of CLHIV and those on treatment in Lesotho, Malawi, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We assessed the total number of CLHIV, CLHIV on antiretroviral treatment (ART), and national and regional ART coverage gaps using 3 data sources: (1) Joint United Nations Programme on HIV/AIDS model-based estimates and national program data used as input values in the models, (2) population-based HIV impact surveys (PHIA), and (3) program data from the President's Emergency Plan for AIDS Relief (PEPFAR)-supported clinics. RESULTS: Across the 7 countries, HIV prevalence among children aged 0-14 years ranged from 0.4% (Uncertainty Bounds (UB) 0.2%-0.6%) to 2.8% (UB: 2.2%-3.4%) according to the PHIA surveys, resulting in estimates of 520,000 (UB: 460,000-580,000) CLHIV in 2016-2017 in the 7 countries. This compared with Spectrum estimates of pediatric HIV prevalence ranging from 0.5% (UB: 0.5%-0.6%) to 3.5% (UB: 3.0%-4.0%) representing 480,000 (UB: 390,000-550,000) CLHIV. CLHIV not on treatment according to the PEPFAR, PHIA, and Spectrum for the countries stood at 48% (UB: 25%-60%), 49% (UB: 37%-50%), and 38% (UB: 24%-47%), respectively. Of 78 regions examined across 7 countries, 33% of regions (PHIA data) or 41% of regions (PEPFAR data) had met the ART coverage target of 81%. CONCLUSIONS: There are substantial gaps in the coverage of HIV treatment in CLHIV in the 7 countries studied according to all sources. There is continued need to identify, engage, and treat infants and children. Important inconsistencies in estimates across the 3 sources warrant in-depth investigation.

BACKGROUND: Sapoviruses are responsible for sporadic and epidemic acute gastroenteritis worldwide. Sapovirus typing protocols have a success rate as low as 43% and relatively few complete sapovirus genome sequences are available to improve current typing protocols. OBJECTIVE/STUDY DESIGN: To increase the number of complete sapovirus genomes to better understand the molecular epidemiology of human sapovirus and to improve the success rate of current sapovirus typing methods, we used deep metagenomics shotgun sequencing to obtain the complete genomes of 68 sapovirus samples from four different countries across the Americas (Guatemala, Nicaragua, Peru and the US). RESULTS: VP1 genotyping showed that all sapovirus sequences could be grouped in the four established genogroups (GI (n=13), GII (n=30), GIV (n=23), GV (n=2)) that infect humans. They include the near-complete genome of a GI.6 virus and a recently reported novel GII.8 virus. Sequences of the complete RNA-dependent RNA polymerase gene could be grouped into three major genetic clusters or polymerase (P) types (GI.P, GII.P and GV.P) with all GIV viruses harboring a GII polymerase. One (GII.P-GII.4) of the new 68 sequences was a recombinant virus with the hotspot between the NS7 and VP1 regions. CONCLUSIONS: Analyses of this expanded database of near-complete sapovirus sequences showed several mismatches in the genotyping primers, suggesting opportunities to revisit and update current sapovirus typing methods.

Background: Sapovirus is one of the primary viral causes of acute gastroenteritis, especially in settings where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Methods: Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and one non-diarrheal stools collected trimonthly from children up to two years of age (n=1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n=440), collected before and after a sapovirus positive sample. Results: The incidence of sapovirus infection in the first and second year of life was 4.3 and 11.1 per 100-child months, respectively. By two years of age, 82% of children had at least one sapovirus infection, and 64% had at least one sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from four genogroups (GI, GII, GIV and GV) were determined. Among genogroups, GI viruses were more frequently found in symptomatic infections than in asymptomatic infections (OR: 3.1 [CI: 1.3-7.4]). Fifty-nine children had serial sapovirus infections but only three had repeated infection of the same genotype. Conclusions: Sapovirus was frequently detected in children with acute gastroenteritis at the community level during the first two years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which need to be taken into account for vaccine development.

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries. The national prevalence of HIV infection in adolescent girls and young women aged 15-24 years, the percentage who were aware of their status, and among those persons who were aware, the percentage who had achieved viral suppression were calculated. The target for viral suppression among all persons with HIV infection is 73% (the product of 90% x 90% x 90%). Among all seven countries, the prevalence of HIV infection among adolescent girls and young women was 3.6%; among those in this group, 46.3% reported being aware of their HIV-positive status, and 45.0% were virally suppressed. Sustained efforts by national HIV and public health programs to diagnose HIV infection in adolescent girls and young women as early as possible to ensure rapid initiation of ART should help achieve epidemic control among adolescent girls and young women.

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.

We report here two complete coding genome sequences of novel genotype GII.8 sapovirus strains identified in diarrhea samples collected from two Peruvian children. The complete coding genome sequences of both GII.8 variants were determined using the Sanger sequencing method.

A total of 6,255 ticks belonging to three genera and six species (Haemaphysalis flava Neumann, Haemaphysalis longicornis Neumann, Haemaphysalis phasiana Saito, Ixodes nipponensis Kitaoka & Saito, Ixodes persulcatus Schulze, and Amblyomma testudinarium Koch) collected from May-August, 2013, at four southwestern provinces in the Republic of Korea (ROK) were submitted to the Armed Forces Research Institute of Medical Sciences and assayed for selected tick-borne pathogens. One pool each of H. flava and H. phasiana was positive by PCR and sequencing for a Francisella-like endosymbiont, while all pools were negative for Francisella tularensis, the causative agent of tularemia.