SARS-CoV-2 Seroprevalence and Vaccine Uptake among Pregnant Women at First Antenatal Care Visits in Malawi.

Many SARS-CoV-2 infections are asymptomatic, thus reported cases underestimate actual cases. To improve estimates, we conducted surveillance for SARS-CoV-2 seroprevalence among pregnant women attending their first antenatal care visit (ANC1) from June 2021 through May 2022. We administered a questionnaire to collect demographic, risk factors, and COVID-19 vaccine status information and tested dried blood spots for SARS-CoV-2 antibodies. Although <1% of ANC1 participants reported having had COVID-19, monthly SARS-CoV-2 seroprevalence increased from 15.4% (95% CI: 10.5-21.5) in June 2021 to 65.5% (95% CI: 55.5-73.7) in May 2022. Although COVID-19 vaccination was available in March 2021, uptake remained low, reaching a maximum of 9.5% (95% CI: 5.7-14.8) in May 2022. Results of ANC1 serosurveillance provided prevalence estimates helpful in understanding this population case burden that was available through self-report and national case reports. To improve vaccine uptake, efforts to address fears and misconceptions regarding COVID-19 vaccines are needed.

Age-disparate and intergenerational sex partnerships and HIV: the role of gender norms among adolescent girls and young women in Malawi.

BACKGROUND: Age-mixing (age-disparate [5-9 years difference] and intergenerational [≥ 10 years difference]) partnerships are hypothesized drivers of HIV in adolescent girls and young women (AGYW; 15-24 years). These partnerships are often associated with increased gender inequities which undermine women's agency and assertiveness. We assessed whether age-mixing partnerships were associated with HIV in Malawi and if endorsement of inequitable gender norms modifies this relationship. METHODS: We analyzed data from the Malawi Population-based HIV Impact Assessment, a nationally representative household survey conducted in 2015-2016. Participants underwent HIV testing and completed questionnaires related to actively endorsed gender norms and sexual risk behavior. We used multivariate logistic regression and multiplicative interaction to assess associations among AGYW who reported the age of their primary sex partner from the last year. RESULTS: The analysis included 1,958 AGYW (mean age = 19.9 years, SD = 0.1), 459 (23.4%) and 131 (6.7%) of whom reported age-disparate and intergenerational partnerships, respectively. AGYW in age-mixing partnerships accounted for 13% of all AGYW and were older, more likely to reside in urban areas, to be married or cohabitating with a partner, and to have engaged in riskier sexual behavior compared with AGYW in age-concordant partnerships (p < 0.05). HIV prevalence among AGYW in age-disparate and intergenerational partnerships was 6.1% and 11.9%, respectively, compared with 3.2% in age-concordant partnerships (p < 0.001). After adjusting for residence, age, education, employment, wealth quintile, and ever been married or cohabitated as married, AGYW in age-disparate and intergenerational partnerships had 1.9 (95% CI: 1.1-3.5) and 3.4 (95% CI: 1.6-7.2) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. Among the 614 (31% of the study group) who endorsed inequitable gender norms, AGYW in age-disparate and intergenerational partnerships had 3.5 (95% CI: 1.1-11.8) and 6.4 (95% CI: 1.5-27.8) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. CONCLUSIONS: In this Malawi general population survey, age-mixing partnerships were associated with increased odds of HIV among AGYW. These findings highlight inequitable gender norms as a potential focus for HIV prevention and could inform interventions targeting structural, cultural, and social constraints of this key group.

Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment.

BACKGROUND: The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi. METHODS: MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted. RESULTS: We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2-15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2-1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4-4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8-74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1-1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4-1.9), were associated higher willingness to use PrEP. CONCLUSIONS: In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.

Trends in HIV prevalence, incidence, and progress towards the UNAIDS 95-95-95 targets in Malawi among individuals aged 15-64 years: population-based HIV impact assessments, 2015-16 and 2020-21.

BACKGROUND: In 2014, UNAIDS set the goal of ending the AIDS epidemic by 2030 through the achievement of testing and treatment cascade targets. To evaluate progress achieved and highlight persisting gaps in HIV epidemic control in Malawi, we aimed to compare key indicators (prevalence, incidence, viral load suppression, and UNAIDS 95-95-95 targets) from the 2015-16 and 2020-21 Malawi Population-based HIV Impact Assessment (PHIA) survey results. METHODS: The Malawi PHIAs were nationally representative, cross-sectional surveys with a two-stage cluster sampling design. The first survey was conducted between Nov 27, 2015, and Aug 26, 2016; the second survey was conducted between Jan 15, 2020, and April 26, 2021. Our analysis included survey participants aged 15-64 years. Participants were interviewed and a 14 mL blood sample was collected and tested for HIV infection using the national rapid testing algorithm. For each survey, we estimated key HIV epidemic indicators and achievement of 95-95-95 targets. The risk ratio (RR) of the indicators between surveys were computed and considered significant at a confidence level of 0·05. All results were weighted, and self-reported awareness and treatment status were adjusted to account for detection of antiretrovirals. FINDINGS: Our analysis included 17 187 participants aged 15-64 years in 2015-16 and 21 208 in 2020-21 who participated in the surveys and blood draw. In the 2020-21 survey, 88·4% (95% CI 86·7-90·0) of people living with HIV were aware of their HIV-positive status; of those aware, 97·8% (97·1-98·5) were on antiretroviral therapy; and of those on treatment, 96·9% (95·9-97·7) were virally suppressed. Between surveys, the national HIV prevalence decreased significantly from 10·6% (10·0-11·2) to 8·9% (8·4-9·5) with RR 0·85 (95% CI 0·78-0·92; p<0·0001). The annual HIV incidence decreased from 0·37% (0·20-0·53) to 0·22% (0·11-0·34) with RR 0·61 (95% CI 0·31-1·20; p=0·15). The population viral load suppression increased from 68·3% (66·0-70·7) in 2015-16 to 87·0% (85·3-88·5) in 2020-21 (RR 1·27 [95% CI 1·22-1·32]; p<0·0001). INTERPRETATION: These results suggest that Malawi had already surpassed the UNAIDS viral load suppression target for 2030 (85·7%) by 2020-21. Through strategies and evidence-informed interventions implemented in the last half decade, especially scale-up of effective HIV treatment, Malawi has made tremendous progress, including decreasing HIV prevalence and incidence and achieving both the second and third 95 targets ahead of 2030. To address the first 95, efforts in HIV diagnosis should focus on males and younger age groups. There is a continued need for effective linkage to care, retention on antiretroviral therapy, and adherence support to maintain and build on progress. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

HIV Recent Infection and Past HIV Testing History Among Newly HIV-Diagnosed 15-24-Year-Olds in Malawi: An Analysis of 2019-2022 HIV Recent Infection Surveillance Data.

Awareness of HIV status in Malawi is 88.3% and lowest among 15-24-year-olds (76.2%). There is a need to understand HIV testing history and transmission in this age group. We analyzed pooled HIV surveillance data to describe testing history and HIV recent infection among 8,389 HIV-positive 15-24-year-olds from 251 sites in Malawi between 2019 and 2022. Most HIV-positive 15-24-year-olds were female; aged 23-24 years; rural residents; and diagnosed at voluntary counseling and testing. No prior HIV testing was reported in 43.5% and 32.9% of 15-19-year-olds and males, respectively. Overall, 4.9% of HIV-positive diagnoses were classified as recent HIV infections, with the highest proportions among breastfeeding women (8.2%); persons tested at sexually transmitted infection clinics (9.0%); persons with a prior negative test within 6 months (13.0%); and 17-18-year-olds (7.3%). Tailored and innovative HIV prevention and testing strategies for young adolescents, young males, and pregnant and breastfeeding women are needed for HIV epidemic control.

Male partner age, viral load, and HIV infection in adolescent girls and young women: evidence from eight sub-Saharan African countries.

OBJECTIVE: We aimed to elucidate the role of partnerships with older men in the HIV epidemic among adolescent girls and young women (AGYW) aged 15-24 years in sub-Saharan Africa. DESIGN: Analysis of Population-based HIV Impact Assessments in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We examined associations between reported partner age and recent HIV infection among AGYW, incorporating male population-level HIV characteristics by age-band. Recent HIV infection was defined using the LAg avidity assay algorithm. Viremia was defined as a viral load of more than 1000 copies/ml, regardless of serostatus. Logistic regression compared recent infection in AGYW with older male partners to those reporting younger partners. Dyadic analysis examined cohabitating male partner age, HIV status, and viremia to assess associations with AGYW infection. RESULTS: Among 17 813 AGYW, increasing partner age was associated with higher odds of recent infection, peaking for partners aged 35-44 (adjusted odds ratio = 8.94, 95% confidence interval: 2.63-30.37) compared with partners aged 15-24. Population-level viremia was highest in this male age-band. Dyadic analyses of 5432 partnerships confirmed the association between partner age-band and prevalent HIV infection (male spousal age 35-44-adjusted odds ratio = 3.82, 95% confidence interval: 2.17-6.75). Most new infections were in AGYW with partners aged 25-34, as most AGYW had partners in this age-band. CONCLUSION: These results provide evidence that men aged 25-34 drive most AGYW infections, but partners over 9 years older than AGYW in the 35-44 age-band confer greater risk. Population-level infectiousness and male age group should be incorporated into identifying high-risk typologies in AGYW.

SARS-CoV-2 Prevalence in Malawi Based on Data from Survey of Communities and Health Workers in 5 High-Burden Districts, October 2020.

To determine early COVID-19 burden in Malawi, we conducted a multistage cluster survey in 5 districts. During October-December 2020, we recruited 5,010 community members (median age 32 years, interquartile range 21-43 years) and 1,021 health facility staff (HFS) (median age 35 years, interquartile range 28-43 years). Real-time PCR-confirmed SARS-CoV-2 infection prevalence was 0.3% (95% CI 0.2%-0.5%) among community and 0.5% (95% CI 0.1%-1.2%) among HFS participants; seroprevalence was 7.8% (95% CI 6.3%-9.6%) among community and 9.7% (95% CI 6.4%-14.5%) among HFS participants. Most seropositive community (84.7%) and HFS (76.0%) participants were asymptomatic. Seroprevalence was higher among urban community (12.6% vs. 3.1%) and HFS (14.5% vs. 7.4%) than among rural community participants. Cumulative infection findings 113-fold higher from this survey than national statistics (486,771 vs. 4,319) and predominantly asymptomatic infections highlight a need to identify alternative surveillance approaches and predictors of severe disease to inform national response.

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.

Characterising persons diagnosed with HIV as either recent or long-term using a cross-sectional analysis of recent infection surveillance data collected in Malawi from September 2019 to March 2020.

OBJECTIVES: In Malawi, a recent infection testing algorithm (RITA) is used to characterise infections of persons newly diagnosed with HIV as recent or long term. This paper shares results from recent HIV infection surveillance and describes distribution and predictors. SETTING: Data from 155 health facilities in 11 districts in Malawi were pooled from September 2019 to March 2020. PARTICIPANTS: Eligible participants were ≥13 years, and newly diagnosed with HIV. Clients had RITA recent infections if the rapid test for recent infection (RTRI) test result was recent and viral load (VL) ≥1000 copies/mL; if VL was <1000 copies/mL the RTRI result was reclassified as long-term. Results were stratified by age, sex, pregnancy/breastfeeding status and district. RESULTS: 13 838 persons consented to RTRI testing and 12 703 had valid RTRI test results and VL results after excluding clients not newly HIV-positive, RTRI negative or missing data (n=1135). A total of 12 365 of the 12 703 were included in the analysis after excluding those whose RTRI results were reclassified as long term (n=338/784 or 43.1%). The remainder, 446/12 703 or 3.5%, met the definition of RITA recent infection. The highest percentage of recent infections was among breastfeeding women (crude OR (COR) 3.2; 95% CI 2.0 to 5.0), young people aged 15-24 years (COR 1.6; 95% CI 1.3 to 1.9) and persons who reported a negative HIV test within the past 12 months (COR 3.3; 95% CI 2.6 to 4.2). Factors associated with recent infection in multivariable analysis included being a non-pregnant female (adjusted OR (AOR) 1.4; 95% CI 1.2 to 1.8), a breastfeeding female (AOR 2.2; 95% CI 1.4 to 3.5), aged 15-24 years (AOR 1.6; 95% CI 1.3 to 1.9) and residents of Machinga (AOR 2.0; 95% CI 1.2 to 3.5) and Mzimba (AOR 2.4; 95% CI 1.3 to 4.5) districts. CONCLUSIONS: Malawi's recent HIV infection surveillance system demonstrated high uptake and identified sub-populations of new HIV diagnoses with a higher percentage of recent infections.

Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.

BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

Community Mobilization Approaches for Large-Scale Public Health Surveys: Experiences from the Population-based HIV Impact Assessment (PHIA) Project.

Community mobilization is an integral process of raising awareness and increasing participation in a specific program. Communities with long-standing mistrust of health research may otherwise be reluctant to participate in surveys originating outside of their locality, particularly when asked to share personal information, provide blood samples, or undergo medical examinations. Here we discuss the community mobilization approaches undertaken by the Population-based HIV Impact Assessment (PHIA) project to optimize participation in surveys across 13 countries of sub-Saharan Africa. The PHIA Project developed a community mobilization strategy to address anticipated community concerns. In each country, a trained cadre of Community Mobilization Coordinators (CMCs) facilitated (1) ongoing communication with leadership and stakeholders at national, provincial/district and local levels; (2) door-to-door visits and group meetings; (3) promotional material dissemination through radio and television jingles and mass social/community media; and (4) the use of public address systems to enhance survey awareness and promote participation. Response rates (RR) were recorded from each survey. The PHIA surveys' mobilization efforts cultivated a receptive environment for data collection. The average household response rate for 13 PHIA surveys was 90.4% and interview RR were consistently over 80%, with women more likely to conduct an interview in all countries except Cote d'Ivoire. 89% of eligible women consented to a blood draw and 81.1% of eligible men consented. The robust and contextualized community mobilization approaches in PHIA were critical for engaging communities in large-scale public health surveys and contributed to high RR in participant interviews and blood draw.

Acceptability and feasibility of HIV recent infection surveillance by healthcare workers using a rapid test for recent infection at HIV testing sites - Malawi, 2019.

BACKGROUND: The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities. SETTING: At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS). METHODS: Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text. RESULTS: We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients. CONCLUSION: This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.

Geospatial Transmission Hotspots of Recent HIV Infection - Malawi, October 2019-March 2020.

Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.† The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)§ and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission.

Performance of a novel rapid test for recent HIV infection among newly-diagnosed pregnant adolescent girls and young women in four high-HIV-prevalence districts-Malawi, 2017-2018.

Tests for recent HIV infection (TRI) distinguish recent from long-term HIV infections using markers of antibody maturation. The limiting antigen avidity enzyme immunoassay (LAg EIA) is widely used with HIV viral load (VL) in a recent infection testing algorithm (RITA) to improve classification of recent infection status, estimate population-level HIV incidence, and monitor trends in HIV transmission. A novel rapid test for recent HIV infection (RTRI), Asanté™, can determine HIV serostatus and HIV recency within minutes on a lateral flow device through visual assessment of test strip or reader device. We conducted a field-based laboratory evaluation of the RTRI among pregnant adolescent girls and young women (AGYW) attending antenatal clinics (ANC) in Malawi.We enrolled pregnant AGYW aged <25 years testing HIV-positive for the first time at their first ANC visit from 121 ANCs in four high-HIV burden districts. Consenting participants provided blood for recency testing using LAg EIA and RTRI, which were tested in central laboratories. Specimens with LAg EIA normalized optical density values ≤2.0 were classified as probable recent infections. RTRI results were based on: (1) visual assessment: presence of a long-term line (LT) indicating non-recent infection and absence of the line indicating recent infection; or (2) a reader; specimens with LT line intensity units <3.0 were classified as probable recent infections. VL was measured for specimens classified as a probable recent infections by either assay; those with HIV-1 RNA ≥1,000 copies/mL were classified as confirmed recent infections. We evaluated the performance of the RTRI by calculating correlation between RTRI and LAg EIA results, and percent agreement and kappa between RTRI and LAg EIA RITA results.Between November 2017 to June 2018, 380 specimens were available for RTRI evaluation; 376 (98.9%) were confirmed HIV-positive on RTRI. Spearman's rho between RTRI and LAg EIA was 0.72 indicating strong correlation. Percent agreement and kappa between RTRI- and LAg EIA-based RITAs were >90% and >0.65 respectively indicating substantial agreement between the RITAs.This was the first field evaluation of an RTRI in sub-Saharan Africa, which demonstrated good performance of the assay and feasibility of integrating RTRI into routine HIV testing services for real-time surveillance of recent HIV infection.

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.

Treatment-adjusted prevalence to assess HIV testing programmes.

Scale-up of human immunodeficiency virus (HIV) testing and antiretroviral therapy (ART) for people living with HIV has been increasing in sub-Saharan Africa. As a result, areas with high HIV prevalence are finding a declining proportion of people testing positive in their national testing programmes. In eastern and southern Africa, where there are settings with adult HIV prevalence of 12% and above, the positivity from national HIV testing services has dropped to below 5%. Identifying those in need of ART is therefore becoming more costly for national HIV programmes. Annual target-setting assumes that national testing positivity rates approximate that of population prevalence. This assumption has generated an increased focus on testing approaches which achieve higher rates of HIV positivity. This trend is a departure from the provider-initiated testing and counselling strategy used early in the global HIV response. We discuss a new indicator, treatment-adjusted prevalence, that countries can use as a practical benchmark for estimating the expected adult positivity in a testing programme when accounting for both national HIV prevalence and ART coverage. The indicator is calculated by removing those people receiving ART from the numerator and denominator of HIV prevalence. Treatment-adjusted prevalence can be readily estimated from existing programme data and population estimates, and in 2019, was added to the World Health Organization guidelines for HIV testing and strategic information. Using country examples from Kenya, Malawi, South Sudan and Zimbabwe we illustrate how to apply this indicator and we discuss the potential public health implications of its use from the national to facility level.

Le dépistage du virus de l'immunodéficience humaine (VIH) et le traitement antirétroviral (TAR) pour les personnes vivant avec le VIH ont connu un véritable essor en Afrique subsaharienne. Par conséquent, les régions touchées par une forte prévalence du VIH détectent un pourcentage moins élevé de personnes testées positives dans leurs programmes de dépistage nationaux. En Afrique orientale et australe, là où certains endroits affichent une prévalence du VIH chez l'adulte égale ou supérieure à 12%, le taux de positivité des services de dépistage nationaux est passé sous la barre des 5%. Identifier les personnes nécessitant un TAR devient donc plus coûteux pour les programmes nationaux consacrés au VIH. Pour définir les objectifs annuels, on part du principe que les taux de positivité nationaux se rapprochent du taux de prévalence au sein de la population. Cette supposition a orienté les démarches vers des méthodes de dépistage permettant d'obtenir des taux de positivité plus élevés; une tendance qui s'écarte de la stratégie des services de dépistage et de conseil à l'initiative des prestataires, utilisée à l'aube de la lutte mondiale contre le VIH. Dans le présent document, nous nous intéressons à un nouvel indicateur, la prévalence ajustée sur le traitement. Cet indicateur peut servir de référence concrète pour les pays qui souhaitent évaluer le taux de positivité attendu chez l'adulte dans un programme de dépistage, en tenant compte de la prévalence du VIH au niveau national ainsi que de la portée du TAR. Le calcul consiste à enlever les personnes recevant un TAR du numérateur et du dénominateur de la prévalence du VIH. La prévalence ajustée sur le traitement peut aisément être déterminée en fonction des données de programme et estimations de population existantes. En 2019, elle a également été ajoutée aux lignes directrices de l'Organisation mondiale de la Santé pour l'information stratégique et le dépistage du VIH. En nous inspirant d'exemples issus du Kenya, du Malawi, du Soudan du Sud et du Zimbabwe, nous expliquons comment employer cet indicateur et abordons les potentielles implications liées à son utilisation en matière de santé publique, en partant du niveau national jusqu'aux établissements.

La ampliación de las pruebas de detección del virus de la inmunodeficiencia humana (VIH) y del tratamiento antirretrovírico (TAR) para las personas infectadas por el VIH ha aumentado en el África subsahariana. En consecuencia, el porcentaje de personas que dan positivo en las pruebas de detección del VIH en los programas nacionales está disminuyendo en las zonas con alta prevalencia del virus. En África meridional y oriental, donde hay entornos con una prevalencia del VIH en adultos del 12 % o superior, la tasa de positividad de los servicios nacionales de pruebas de detección del VIH ha descendido a menos del 5 %. Por lo tanto, la identificación de las personas que necesitan TAR es cada vez más costosa para los programas nacionales de VIH. El establecimiento de objetivos anuales supone que las tasas de positividad de las pruebas nacionales se aproximan a las de la prevalencia de la población. Esta suposición ha generado una mayor atención a los enfoques de las pruebas que logran tasas más altas de positividad del VIH. Esta tendencia se aleja de la estrategia del asesoramiento y las pruebas que iniciaron los proveedores y que se utilizó al principio de la respuesta mundial al VIH. Se analiza un nuevo indicador, la prevalencia ajustada según el tratamiento, que los países pueden emplear como punto de referencia práctico para estimar la tasa de positividad esperada en adultos en un programa de pruebas de detección cuando se tiene en cuenta tanto la prevalencia nacional del VIH como la cobertura del TAR. El indicador se calcula eliminando del numerador y el denominador de la prevalencia del VIH a las personas que reciben TAR. La prevalencia ajustada según el tratamiento se puede estimar con facilidad a partir de los datos de los programas existentes y de las estimaciones de población, además, en 2019, se incluyó en las directrices de la Organización Mundial de la Salud para las pruebas de detección del VIH y en la información estratégica. A través de ejemplos de países como Kenia, Malaui, Sudán meridional y Zimbabue, se demuestra cómo aplicar este indicador y se discuten las posibles implicaciones para la salud pública de su uso desde el nivel nacional hasta el de los centros.

Naomi: a new modelling tool for estimating HIV epidemic indicators at the district level in sub-Saharan Africa.

INTRODUCTION: HIV planning requires granular estimates for the number of people living with HIV (PLHIV), antiretroviral treatment (ART) coverage and unmet need, and new HIV infections by district, or equivalent subnational administrative level. We developed a Bayesian small-area estimation model, called Naomi, to estimate these quantities stratified by subnational administrative units, sex, and five-year age groups. METHODS: Small-area regressions for HIV prevalence, ART coverage and HIV incidence were jointly calibrated using subnational household survey data on all three indicators, routine antenatal service delivery data on HIV prevalence and ART coverage among pregnant women, and service delivery data on the number of PLHIV receiving ART. Incidence was modelled by district-level HIV prevalence and ART coverage. Model outputs of counts and rates for each indicator were aggregated to multiple geographic and demographic stratifications of interest. The model was estimated in an empirical Bayes framework, furnishing probabilistic uncertainty ranges for all output indicators. Example results were presented using data from Malawi during 2016-2018. RESULTS: Adult HIV prevalence in September 2018 ranged from 3.2% to 17.1% across Malawi's districts and was higher in southern districts and in metropolitan areas. ART coverage was more homogenous, ranging from 75% to 82%. The largest number of PLHIV was among ages 35 to 39 for both women and men, while the most untreated PLHIV were among ages 25 to 29 for women and 30 to 34 for men. Relative uncertainty was larger for the untreated PLHIV than the number on ART or total PLHIV. Among clients receiving ART at facilities in Lilongwe city, an estimated 71% (95% CI, 61% to 79%) resided in Lilongwe city, 20% (14% to 27%) in Lilongwe district outside the metropolis, and 9% (6% to 12%) in neighbouring Dowa district. Thirty-eight percent (26% to 50%) of Lilongwe rural residents and 39% (27% to 50%) of Dowa residents received treatment at facilities in Lilongwe city. CONCLUSIONS: The Naomi model synthesizes multiple subnational data sources to furnish estimates of key indicators for HIV programme planning, resource allocation, and target setting. Further model development to meet evolving HIV policy priorities and programme need should be accompanied by continued strengthening and understanding of routine health system data.

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.

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.