HIV Incidence in Botswana Rural Communities With High Antiretroviral Treatment Coverage: Results From the Botswana Combination Prevention Project, 2013-2017.

BACKGROUND AND SETTING: The Botswana Combination Prevention Project demonstrated a 30% reduction in community HIV incidence through expanded HIV testing, enhanced linkage to care, and universal antiretroviral treatment and exceeded the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. We report rates and characteristics of incident HIV infections. METHODS: The Botswana Combination Prevention Project was a community-randomized controlled trial conducted in 30 rural/periurban Botswana communities from 2013 to 2017. Home-based and mobile HIV-testing campaigns were conducted in 15 intervention communities, with 39% of participants testing at least twice. We assessed the HIV incidence rate [IR; number of new HIV infections per 100 person-years (py) at risk] among repeat testers and risk factors with a Cox proportional hazards regression model. RESULTS: During 27,517 py, 195 (women: 79%) of 18,597 became HIV-infected (0.71/100 py). Women had a higher IR (1.01/100 py; 95% confidence interval: 0.99 to 1.02) than men (0.34/100 py; 95% confidence interval: 0.33 to 0.35). The highest IRs were among women aged 16-24 years (1.87/100 py) and men aged 25-34 years (0.56/100 py). The lowest IRs were among those aged 35-64 years (women: 0.41/100 py; men: 0.20/100 py). The hazard of incident infection was the highest among women aged 16-24 years (hazard ratio = 7.05). Sex and age were significantly associated with incidence (both P < 0.0001). CONCLUSIONS: Despite an overall reduction in HIV incidence and approaching the United Nations Programme on HIV/AIDS 95-95-95 targets, high HIV incidence was observed in adolescent girls and young women. These findings highlight the need for additional prevention services (pre-exposure prophylaxis and DREAMS) to achieve epidemic control in this subpopulation and increased efforts with men with undiagnosed HIV.

To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approach.

BACKGROUND: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. METHODS: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression. RESULTS: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. CONCLUSIONS: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. CLINICAL TRIAL NUMBER: NCT01965470.

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic.

Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.

INTRODUCTION: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study. METHODS: BCPP was designed to evaluate the impact of prevention interventions on HIV incidence in 30 communities in Botswana. We followed a longitudinal cohort of newly identified and known HIV-positive persons not on antiretroviral therapy (ART) identified through community-based testing activities through BCPP and referred with appointments to local HIV clinics in 15 intervention communities. Those who did not keep the first or follow-up appointments were tracked and traced through phone and home contacts. Improvements to service delivery models in the intervention clinics were also implemented. RESULTS: A total of 3,657 newly identified or HIV-positive persons not on ART were identified and referred to their local HIV clinic; 90% (3,282/3,657) linked to care and of those, 93% (3,066/3,282) initiated treatment. Near the end of the study, 221 persons remained >90 days late for appointments or missing. Tracing efforts identified 54/3,066 (2%) persons who initiated treatment but died, and 106/3,066 (3%) persons were located and returned to treatment. At study end, 61/3,066 (2%) persons remained missing and were never reached. Overall, 2,951 (98%) persons living with HIV (PLHIV) who initiated treatment were still alive, retained in care and still receiving ART out of the 3,001 persons alive at the end of the study. Of those on ART, 2,854 (97%) had current VL results and 2,784 (98%) of those were virally suppressed at study end. CONCLUSIONS: This study achieved high rates of linkage, treatment initiation, retention and VL coverage and suppression in a cohort of newly identified and known PLHIV not on ART. Tracking and tracing interventions effectively identified those persons who needed more resource intensive follow-up. The interventions implemented to improve service delivery and data quality may have also contributed to high linkage and retention rates. Clinical trial number: NCT01965470.

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID-19 pandemic and beyond.

INTRODUCTION: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases. DISCUSSION: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic. CONCLUSIONS: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.

Laboratory medicine in Africa since 2008: then, now, and the future.

The Maputo Declaration of 2008 advocated for commitment from global stakeholders and national governments to prioritise support and harmonisation of laboratory systems through development of comprehensive national laboratory strategies and policies in sub-Saharan Africa. As a result, HIV laboratory medicine in Africa has undergone a transformation, and substantial improvements have been made in diagnostic services, networks, and institutions, including the development of a competent workforce, introduction of point-of-care diagnostics, and innovative quality improvement programmes that saw more than 1100 laboratories enrolled and 44 accredited to international standards. These improved HIV laboratories can now be used to combat emerging continental and global health threats in the decades to come. For instance, the unprecedented Ebola virus disease outbreak in west Africa exposed the severe weaknesses in the overall national health systems in affected countries. It is now possible to build robust health-care systems in Africa and to combat emerging continental and global health threats in the future. In this Personal View, we aim to describe the remarkable transformation that has occurred in laboratory medicine to combat HIV/AIDS and improve global health in sub-Saharan Africa since 2008.

Expansion of Viral Load Testing and the Potential Impact on HIV Drug Resistance.

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation.

Design of the HPTN 065 (TLC-Plus) study: A study to evaluate the feasibility of an enhanced test, link-to-care, plus treat approach for HIV prevention in the United States.

Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression. The HPTN 065 (Test, Link-to-Care Plus Treat [TLC-Plus]) study was designed to determine the feasibility of the "test and treat" approach in the United States. Methods HPTN 065 was conducted in two intervention communities, Bronx, NY, and Washington, DC, along with four non-intervention communities, Chicago, IL; Houston, TX; Miami, FL; and Philadelphia, PA. The study consisted of five components: (1) exploring the feasibility of expanded HIV testing via social mobilization and the universal offer of testing in hospital settings, (2) evaluating the effectiveness of financial incentives to increase linkage to care, (3) evaluating the effectiveness of financial incentives to increase viral suppression, (4) evaluating the effectiveness of a computer-delivered intervention to decrease risk behavior in HIV-positive patients in healthcare settings, and (5) administering provider and patient surveys to assess knowledge and attitudes regarding the use of antiretroviral therapy for prevention and the use of financial incentives to improve health outcomes. The study used observational cohorts, cluster and individual randomization, and made novel use of the existing national HIV surveillance data infrastructure. All components were developed with input from a community advisory board, and pragmatic methods were used to implement and assess the outcomes for each study component. Results A total of 76 sites in Washington, DC, and the Bronx, NY, participated in the study: 37 HIV test sites, including 16 hospitals, and 39 HIV care sites. Between September 2010 and December 2014, all study components were successfully implemented at these sites and resulted in valid outcomes. Our pragmatic approach to the study design, implementation, and the assessment of study outcomes allowed the study to be conducted within established programmatic structures and processes. In addition, it was successfully layered on the ongoing standard of care and existing data infrastructure without disrupting health services. Conclusion The HPTN 065 study demonstrated the feasibility of implementing and evaluating a multi-component "test and treat" trial that included a large number of community sites and involved pragmatic approaches to study implementation and evaluation.

Status and methodology of publicly available national HIV care continua and 90-90-90 targets: A systematic review.

BACKGROUND: In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) issued treatment goals for human immunodeficiency virus (HIV). The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART), and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target. METHODS AND FINDINGS: For the period 2010-2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO), UNAIDS reports, national surveillance and program reports, United States President's Emergency Plan for AIDS Relief (PEPFAR) Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV) who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010-2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54%) of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden) were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia) were within 12% and 10% of achieving the 90-90-90 target for "on ART" and for "viral suppression," respectively. The limitations to consider when interpreting the results include significant variation in methods used to determine national continua and the possibility that complete continua were not available through our comprehensive search of the public domain. CONCLUSIONS: Relatively few complete national continua of care are available in the public domain, and there is considerable variation in the methods for determining progress towards the 90-90-90 target. Despite bearing the highest HIV burden, national care continua from sub-Saharan Africa were less likely to be in the public domain. A standardized monitoring and evaluation approach could improve the use of scarce resources to achieve 90-90-90 through improved transparency, accountability, and efficiency.

Progress with Scale-Up of HIV Viral Load Monitoring - Seven Sub-Saharan African Countries, January 2015-June 2016.

The World Health Organization (WHO) recommends viral load testing as the preferred method for monitoring the clinical response of patients with human immunodeficiency virus (HIV) infection to antiretroviral therapy (ART) (1). Viral load monitoring of patients on ART helps ensure early diagnosis and confirmation of ART failure and enables clinicians to take an appropriate course of action for patient management. When viral suppression is achieved and maintained, HIV transmission is substantially decreased, as is HIV-associated morbidity and mortality (2). CDC and other U.S. government agencies and international partners are supporting multiple countries in sub-Saharan Africa to provide viral load testing of persons with HIV who are on ART. This report examines current capacity for viral load testing based on equipment provided by manufacturers and progress with viral load monitoring of patients on ART in seven sub-Saharan countries (Côte d'Ivoire, Kenya, Malawi, Namibia, South Africa, Tanzania, and Uganda) during January 2015-June 2016. By June 2016, based on the target numbers for viral load testing set by each country, adequate equipment capacity existed in all but one country. During 2015, two countries tested >85% of patients on ART (Namibia [91%] and South Africa [87%]); four countries tested <25% of patients on ART. In 2015, viral suppression was >80% among those patients who received a viral load test in all countries except Côte d'Ivoire. Sustained country commitment and a coordinated global effort is needed to reach the goal for viral load monitoring of all persons with HIV on ART.

Temporal association between expanded HIV testing and improvements in population-based HIV/AIDS clinical outcomes, District of Columbia.

In 2006, the District of Columbia Department of Health (DC DOH) launched initiatives promoting routine HIV testing and improved linkage to care in support of revised the Centers for Disease Control and Prevention (CDC) HIV-testing guidelines. An ecological analysis was conducted using population-based surveillance data to determine whether these efforts were temporally associated with increased and earlier identification of HIV/AIDS cases and improved linkages to care. Publically funded HIV-testing data and HIV/AIDS surveillance data from 2005 to 2009 were used to measure the number of persons tested, new diagnoses, timing of entry into care, CD4 at diagnosis and rates of progression to AIDS. Tests for trend were used to determine whether statistically significant changes in these indicators were observed over the five-year period. Results indicated that from 2005 to 2009, publically funded testing increased 4.5-fold; the number of newly diagnosed HIV/AIDS cases remained relatively constant. Statistically significant increases in the proportion of cases entering care within three months of diagnosis were observed (p < 0.0001). Median CD4 counts at diagnosis increased over the five-year time period from 346 to 379 cells/µL. The proportion of cases progressing from HIV to AIDS and diagnosed with AIDS initially, decreased significantly (both p < 0.0001). Routine HIV testing and linkage to care efforts in the District of Columbia were temporally associated with earlier diagnoses of cases, more timely entry into HIV-specialized care, and a slowing of HIV disease progression. The continued use of surveillance data to measure the community-level impact of other programmatic initiatives including test and treat strategies will be critical in monitoring the response to the District's HIV epidemic.

Implementing a novel citywide rapid HIV testing campaign in Washington, D.C.: findings and lessons learned.

OBJECTIVES: In June 2006, the District of Columbia (DC) Department of Health launched a citywide rapid HIV screening campaign. Goals included raising HIV awareness, routinizing rapid HIV screening, identifying previously unrecognized infections, and linking positives to care. We describe findings from this seminal campaign and identify lessons learned. METHODS: We applied a mixed-methods approach using quantitative analysis of client data forms (CDFs) and qualitative evaluation of focus groups with DC residents. We measured characteristics and factors associated with client demographics, test results, and community perceptions regarding the campaign. RESULTS: Data were available on 38,586 participants tested from July 2006 to September 2007. Of those, 68% had previously tested for HIV (44% within the last 12 months) and 23% would not have sought testing had it not been offered. Overall, 662 (1.7%) participants screened positive on the OraQuick® Advance™ rapid HIV test, with non-Hispanic black people, transgenders, and first-time testers being significantly more likely to screen positive for HIV than white people, males, and those tested within the last year, respectively. Of those screening positive for HIV, 47% had documented referrals for HIV care and treatment services. Focus groups reported continued stigma regarding HIV and minimal community saturation of the campaign. CONCLUSIONS: This widespread campaign tested thousands of people and identified hundreds of HIV-infected individuals; however, referrals to care were lower than anticipated, and awareness of the campaign was limited. Lessons learned through this scale-up of population-based HIV screening resulted in establishing citywide HIV testing processes that laid the foundation for the implementation of test-and-treat activities in DC.

Use of the community viral load as a population-based biomarker of HIV burden.

OBJECTIVES: Recent data suggest that community viral load (CVL) can be used as a population-level biomarker for HIV transmission and its reduction may be associated with a decrease in HIV incidence. Given the magnitude of the HIV epidemic in Washington, District of Columbia, we sought to measure the District of Columbia's CVL. DESIGN: An ecological analysis was conducted. METHODS: Mean and total CVL were calculated using the most recent viral load for prevalent HIV/AIDS cases reported to District of Columbia HIV/AIDS surveillance through 2008. Univariate and multivariable analyses were conducted to assess differences in CVL availability, mean CVL, proportion of undetectable viral loads, and 5-year trends in mean CVL and new HIV/AIDS diagnoses. Geospatial analysis was used to map mean CVL and selected indicators of socioeconomic status by geopolitical designation. RESULTS: Among 15,467 HIV/AIDS cases alive from 2004 to 2008, 48.2% had at least one viral load reported. Viral load data completeness increased significantly over the 5 years (P < 0.001). Mean CVL significantly decreased over time (P < 0.0001). At the end of 2008, the mean CVL was 33,847 copies/ml; 57.4% of cases had undetectable viral loads. Overlaps in the geographic distribution of CVL by census tract were observed with the highest means observed in areas with high poverty rates and low high school diploma rates. CONCLUSION: Mean and total CVL provide markers of access to care and treatment, are indicators of the population's viral burden, and are useful in assessing trends in local HIV/AIDS epidemics. Measurement of CVL is a novel tool for assessing the potential impact of population-level HIV prevention and treatment interventions.

Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations.

BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

High prevalence of substance use among heterosexuals living in communities with high rates of AIDS and poverty in Washington, DC.

OBJECTIVES: To assess the prevalence and patterns of substance use, HIV prevalence, and sexual risk behaviors in a community-based sample of heterosexuals recruited from areas at high risk for HIV/AIDS and poverty in Washington, DC. METHODS: Community-recruited heterosexuals aged 18-50 from areas of high AIDS and poverty rates in DC were analyzed. Based on past 12 months use, participants were hierarchically classified into five groups: (1) ever injection drug use (IDU); (2) non-injection crack; (3) non-injection heroin and cocaine; (4) marijuana; and (5) no drug use. Sexual behaviors and HIV serology were also assessed. RESULTS: Of 862 participants, 40% were men, most were Black and unemployed, and more than half had ever been incarcerated. Prevalence of past year substance use was high: binge drinking (59%); marijuana (50%); non-injection crack (28%); heroin and/or cocaine injection (28%), non-injection cocaine (13%); and ecstasy (13%). In the hierarchical classification, 25% were ever IDU, 15% non-injection crack users, 2% non-injection heroin and/or cocaine users, 31% marijuana users, and 27% reported no drug use. Overall HIV seroprevalence was 5.7% and differed by drug use group-9.5%, 11.1%, 1.8%, 1.6%, and 3.2%, respectively. Nearly half reported having ≥3 sex partners in the past year; 20% reported exchange partners, and 69% had concurrent sex partners. CONCLUSION: Estimated prevalence of substance use in this heterosexual population was high. HIV prevalence among IDUs and non-injection crack users was higher than the estimated population prevalence in Washington, DC. Sexual behaviors above and beyond drug use are likely to be driving HIV transmission.

Elevated HIV prevalence despite lower rates of sexual risk behaviors among black men in the District of Columbia who have sex with men.

The District of Columbia (DC) has among the highest HIV/AIDS rates in the United States, with 3.2% of the population and 7.1% of black men living with HIV/AIDS. The purpose of this study was to examine HIV risk behaviors in a community-based sample of men who have sex with men (MSM) in DC. Data were from the National HIV Behavioral Surveillance system. MSM who were 18 years were recruited via venue-based sampling between July 2008 and December 2008. Behavioral surveys and rapid oral HIV screening with OraQuick ADVANCE ½ (OraSure Technologies, Inc., Bethlehem, PA) with Western blot confirmation on positives were collected. Factors associated with HIV positivity and unprotected anal intercourse were identified. Of 500 MSM, 35.6% were black. Of all men, 14.1% were confirmed HIV positive; 41.8% of these were newly identified HIV positive. Black men (26.0%) were more likely to be HIV positive than white (7.9%) or Latino/Asian/other (6.5%) men (p<0.001). Black men had fewer male sex partners than non-black, fewer had ever engaged in intentional unprotected anal sex, and more used condoms at last anal sex. Black men were less likely to have health insurance, have been tested for HIV, and disclose MSM status to health care providers. Despite significantly higher HIV/AIDS rates, black MSM in DC reported fewer sexual risks than non-black. These findings suggest that among black MSM, the primary risk of HIV infection results from nontraditional sexual risk factors, and may include barriers to disclosing MSM status and HIV testing. There remains a critical need for more information regarding reasons for elevated HIV among black MSM in order to inform prevention programming.