A tale of two countries: progress towards UNAIDS 90‐90‐90 targets in Botswana and Australia

UNAIDS 90‐90‐90 targets and Fast‐Track commitments are presented as precursors to ending the AIDS epidemic by 2030, through effecting a 90% reduction in new HIV infections and AIDS‐related deaths from 2010 levels (HIV epidemic control). Botswana, a low to middle‐income country with the third‐highest HIV prevalence, and Australia, a low‐prevalence high‐income country with an epidemic concentrated among men who have sex with men (MSM), have made significant strides towards achieving the UNAIDS 90‐90‐90 targets. These two countries provide lessons for different epidemic settings. This paper discusses the lessons that can be drawn from Botswana and Australia with respect to their success in HIV testing, treatment, viral suppression and other HIV prevention strategies for HIV epidemic control. Botswana and Australia are on target to achieving the 90‐90‐90 targets for HIV epidemic control, made possible by comprehensive HIV testing and treatment programmes in the two countries. As of 2015, 70% of all people assumed to be living with HIV had viral suppression in Botswana and Australia. However, HIV incidence remains above one per cent in the general population in Botswana and in MSM in Australia. The two countries have demonstrated that rapid HIV testing that is accessible and targeted at key and vulnerable populations is required in order to continue identifying new HIV infections. All citizens living with HIV in both countries are eligible for antiretroviral therapy (ART) and viral load monitoring through government‐funded programmes. Notwithstanding their success in reducing HIV transmission to date, programmes in both countries must continue to be supported at current levels to maintain epidemic suppression. Scaled HIV testing, linkage to care, universal ART, monitoring patients on treatment over and above strengthened HIV prevention strategies (e.g. male circumcision and pre‐exposure prophylaxis) will all continue to require funding. The progress that Botswana and Australia have made towards meeting the 90‐90‐90 targets is commendable. However, in order to reduce HIV incidence significantly towards 2030, there is a need for sustained HIV testing, linkage to care and high treatment coverage. Botswana and Australia provide useful lessons for developing countries with generalized epidemics and high‐income countries with concentrated epidemics

Outcomes of the Botswana national HIV/AIDS treatment programme from 2002 to 2010: a longitudinal analysis

Background Short-term mortality rates among patients with HIV receiving antiretroviral therapy (ART) in sub- Saharan Africa are higher than those recorded in high-income countries, but systematic long-term comparisons have not been made because of the scarcity of available data. We analysed the eff ect of the implementation of Botswana’s national ART programme, known as Masa, from 2002 to 2010. Methods The Masa programme started on Jan 21, 2002. Patients who were eligible for ART according to national guidelines had their data collected prospectively through a clinical information system developed by the Botswana Ministry of Health. A dataset of all available electronic records for adults (≥18 years) who had enrolled by April 30, 2010, was extracted and sent to the study team. All data were anonymised before analysis. The primary outcome was mortality. To assess the eff ect of loss to follow-up, we did a series of sensitivity analyses assuming varying proportions of the population lost to follow-up to be dead. Findings We analysed the records of 126 263 patients, of whom 102 713 had documented initiation of ART. Median follow-up time was 35 months (IQR 14–56), with a median of eight follow-up visits (4–14). 15 270 patients were deemed lost to follow-up by the end of the study. 63% (78 866) of the study population were women; median age at baseline was 34 years for women (IQR 29–41) and 38 years for men (33–45). 10 230 (8%) deaths were documented during the 9 years of the study. Mortality was highest during the fi rst 3 months after treatment initiation at 12·8 deaths per 100 person-years (95% CI 12·4–13·2), but decreased to 1·16 deaths per 100 person-years (1·12–1·2) in the second year of treatment, and to 0·15 deaths per 100 person-years (0·09–0·25) over the next 7 years of follow-up. In each calendar year after the start of the Masa programme in 2002, average CD4 cell counts at enrolment increased (from 101 cells/μL [IQR 44–156] in 2002, to 191 cells/μL [115–239] in 2010). In each year, the proportion of the total enrolled population who died in that year decreased, from 63% (88 of 140) in 2002, to 0·8% (13 of 1599) in 2010. A sensitivity analysis assuming that 60% of the population lost to follow-up had died gave 3000 additional deaths, increasing overall mortality from 8% to 11–13%. Interpretation The Botswana national HIV/AIDS treatment programme reduced mortality among adults with HIV to levels much the same as in other low-income or middle-income countries

Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after study.

BACKGROUND: Ensuring that individuals who are living with HIV rapidly initiate antiretroviral therapy (ART) is an essential step in meeting the 90-90-90 targets. We evaluated the feasibility and outcomes of rapid ART initiation in the Botswana Combination Prevention Project (BCPP). We aimed to establish whether simplified ART initiation with the offer of same-day treatment could increase uptake and reduce time from clinic linkage to treatment initiation, while maintaining rates of retention in care and viral suppression. METHODS: We did a quasi-experimental before and after study with use of data from the BCPP. The BCPP was a community-randomised HIV-prevention trial done in 30 communities across Botswana from Oct 1, 2013, to June 30, 2018. Participants in the 15 intervention clusters, who were HIV-positive and not already taking ART were offered universal HIV-treatment and same-day ART with a dolutegravir-based regimen at first clinic visit. This rapid ART intervention was implemented mid-way through the trial on June 1, 2016, enabling us to determine the effect of rapid ART guidelines on time to ART initiation and rates of retention in care and viral suppression at 1 year in the BCPP intervention group. FINDINGS: We assessed 1717 adults linked to study clinics before rapid ART introduction and 800 after rapid ART introduction. During the rapid ART period, 457 (57·1%, 95% CI 53·7-60·6) individuals initiated ART within 1 day of linkage, 589 (73·7%, 70·6-76·7) of 799 within 1 week, 678 (84·9%, 82·4-87·3) of 799 within 1 month, and 744 (93·5%, 91·6-95·1) of 796 within 1 year. Before the introduction of rapid ART, 163 (9·5%, 95% CI 8·2-11·0) individuals initiated ART within 1 day of linkage, 276 (16·1%, 14·4-17·9) within 1 week, 839 (48·9%, 46·5-51·3) within 1 month, and 1532 (89·2%, 87·7-90·6) within 1 year. 1 year after ART initiation, 1472 (90·5%, 87·4-92·8) of 1627 individuals who linked in the standard ART period were in care and had a viral load of less than 400 copies per mL, compared with 578 (91·6%, 88·1-94·1) of 631 in the rapid ART period (risk ratio 1·01, 95% CI 0·92-1·11). INTERPRETATION: Our findings provide support for the WHO recommendations for rapid ART initiation, and add to the accumulating evidence showing the feasibility, acceptability, and safety of rapid ART initiation in low-income and middle-income country settings. FUNDING: US President's Emergency Plan for AIDS Relief

Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes.

OBJECTIVE(S): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 cell counts ≤200 cells/μl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. DESIGN: A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment. METHODS: Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 cell counts ≤200 vs. >200 cells/μl). RESULTS: Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7-18.8%] of study participants had advanced HIV disease (CD4 cell counts ≤200 cells/μl) at time of clinic linkage. Men were significantly more likely to present with CD4 cell counts 200 cells/μl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5-2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4-3.2 >35 vs. <25 years). Patients with CD4 cell counts 200 cells/μl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). CONCLUSION: Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care

Comparison of knowledge of HIV status and treatment coverage between non-citizens and citizens: Botswana Combination Prevention Project (BCPP).

INTRODUCTION: Non-citizens often face barriers to HIV care and treatment. Quantifying knowledge of positive HIV status and antiretroviral therapy (ART) coverage among non-citizens in a high HIV-prevalence country like Botswana that is close to achieving UNAIDS "90-90-90" targets may expose important gaps in achieving universal HIV testing and treatment. METHODS: The Botswana Combination Prevention Project (BCPP) is a pair-matched cluster-randomized trial evaluating the impact of prevention interventions on HIV incidence in 30 rural or peri-urban communities. Community case finding and HIV testing were conducted in home and mobile venues in 15 intervention communities from October 2013-September 2017. In this secondary analysis, we compared HIV positivity, knowledge of positive HIV-status, and ART status among all citizens and non-citizens assessed at intake in the intervention communities. RESULTS: HIV status was assessed in 57,556 residents in the intervention communities; 4% (n = 2,463) were non-citizens. Five communities accounted for 81% of the total non-citizens assessed. A lower proportion of non-citizens were HIV-positive (15%; n = 369) compared to citizens (21%; n = 11,416) [p = 0.026]; however, a larger proportion of non-citizens did not know their HIV-positive status prior to BCPP testing (75%) as compared to citizens (15%) [p = 0.003]. Among residents with knowledge of their HIV-positive status before BCPP, 79% of the non-citizens (72/91) were on ART compared to 86% (8,267/9,652) of citizens (p = 0.137). CONCLUSIONS: Although non-citizens were less likely to know their HIV-positive status compared to citizens, there were no differences in treatment uptake among non-citizens and citizens who knew their status. Designing interventions for non-citizens that provide HIV testing and treatment services commensurate to that of citizens as well as targeting communities with the largest number of non-citizens may help close a meaningful gap in the HIV care cascade and ensure ethical treatment for all HIV-positive persons. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01965470 (Botswana Combination Prevention Project)

Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial

BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention

Impact of Health System Inputs on Health Outcome: A Multilevel Longitudinal Analysis of Botswana National Antiretroviral Program (2002-2013).

To measure the association between the number of doctors, nurses and hospital beds per 10,000 people and individual HIV-infected patient outcomes in Botswana.Analysis of routinely collected longitudinal data from 97,627 patients who received ART through the Botswana National HIV/AIDS Treatment Program across all 24 health districts from 2002 to 2013. Doctors, nurses, and hospital bed density data at district-level were collected from various sources.A multilevel, longitudinal analysis method was used to analyze the data at both patient- and district-level simultaneously to measure the impact of the health system input at district-level on probability of death or loss-to-follow-up (LTFU) at the individual level. A marginal structural model was used to account for LTFU over time.Increasing doctor density from one doctor to two doctors per 10,000 population decreased the predicted probability of death for each patient by 27%. Nurse density changes from 20 nurses to 25 nurses decreased the predicted probability of death by 28%. Nine percent decrease was noted in predicted mortality of an individual in the Masa program for every five hospital bed density increase.Considerable variation was observed in doctors, nurses, and hospital bed density across health districts. Predictive margins of mortality and LTFU were inversely correlated with doctor, nurse and hospital bed density. The doctor density had much greater impact than nurse or bed density on mortality or LTFU of individual patients. While long-term investment in training more healthcare professionals should be made, redistribution of available doctors and nurses can be a feasible solution in the short term

High HIV-1 RNA among Newly Diagnosed People in Botswana

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