Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 38 Records) |
Query Trace: Lockman S[original query] |
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Prevalence and control of hypertension in a high HIV-prevalence setting, insights from a population based study in Botswana
Mosepele M , Bennett K , Gaolathe T , Makhema JM , Mmalane M , Holme MP , Lebelonyane R , Ometoruwa O , Mills LA , Powis KM , Leidner J , Jarvis JN , Tapela NM , Masupe T , Mokgatlhe L , Triant VA , Wirth KE , Moshomo T , Lockman S . Sci Rep 2023 13 (1) 17814 In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets. |
Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial (preprint)
Magosi LE , Zhang Y , Golubchik T , DeGruttola V , Tchetgen Tchetgen E , Novitsky V , Moore J , Bachanas P , Segolodi T , Lebelonyane R , Pretorius Holme M , Moyo S , Makhema J , Lockman S , Fraser C , Essex MM , Lipsitch M . medRxiv 2021 2021.06.19.21259186 Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV- intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3] versus 5% [0.9 – 22.9]) compatible with a benefit from treatment-as-prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was supported by the National Institute of General Medical Sciences (U54GM088558); the Fogarty International Center (FIC) of the U.S. National Institutes of Health (D43 TW009610); and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) (Cooperative agreements U01 GH000447 and U2G GH001911).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 trial was approved by the Botswana Health Research and Development Committee, the institutional review board of the Centers for Disease Control and Prevention and the Harvard School of Public Health Office of Regulatory Affairs and Research Compliance; and was monitored by a data and safety monitoring board and Westat. Written informed consent for enrollment in the trial and viral HIV genotyping was obtained from all participants.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).YesI 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.YesAll relevant data are within the paper and the Supplemental Notes, figures and tables. HIV-1 reads are available on reasonable request through the PANGEA consortium (www.pangea-hiv.org) |
Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana.
Bhebhe L , Moyo S , Gaseitsiwe S , Pretorius-Holme M , Yankinda EK , Manyake K , Kgathi C , Mmalane M , Lebelonyane R , Gaolathe T , Bachanas P , Ussery F , Letebele M , Makhema J , Wirth KE , Lockman S , Essex M , Novitsky V , Ragonnet-Cronin M . BMC Infect Dis 2022 22 (1) 710 BACKGROUND: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data. METHODS: As part of the Botswana Combination Prevention Project, 20% of households in 30 villages were tested for HIV and followed from 2013 to 2018. A total of 12,610 participants were enrolled, 3596 tested HIV-positive at enrolment, and 147 participants acquired HIV during the trial. Extensive socio-demographic and behavioural data were collected from participants and next-generation sequences were generated for HIV-positive cases. We compared three groups of participants: (1) those previously known to be HIV-positive at enrolment (n = 2995); (2) those newly diagnosed at enrolment (n = 601) and (3) those who tested HIV-negative at enrolment but tested HIV-positive during follow-up (n = 147). We searched for differences in demographic and behavioural factors between known and newly diagnosed group using logistic regression. We also compared the topology of each group in HIV-1 phylogenies and used a genetic diversity-based algorithm to classify infections as recent (< 1 year) or chronic (≥ 1 year). RESULTS: Being male (aOR = 2.23) and younger than 35 years old (aOR = 8.08) was associated with undiagnosed HIV infection (p < 0.001), as was inconsistent condom use (aOR = 1.76). Women were more likely to have undiagnosed infections if they were married, educated, and tested frequently. For men, being divorced increased their risk. The genetic diversity-based algorithm classified most incident infections as recent (75.0%), but almost none of known infections (2.0%). The estimated proportion of recent infections among new diagnoses was 37.0% (p < 0.001). CONCLUSION: Our results indicate that those with undiagnosed infections are likely to be young men and women who do not use condoms consistently. Among women, several factors were predictive: being married, educated, and testing frequently increased risk. Men at risk were more difficult to delineate. A sizeable proportion of undiagnosed infections were recent based on a genetic diversity-based classifier. In the era of "test and treat all", pre-exposure prophylaxis may be prioritized towards individuals who self-identify or who can be identified using these predictors in order to halt onward transmission in time. |
HIV incidence in Botswana rural communities with high antiretroviral treatment coverage: Results from the Botswana Combination Prevention Project, 2013-2017
Ussery F , Bachanas P , Alwano MG , Lebelonyane R , Block L , Wirth K , Ussery G , Sento B , Gaolathe T , Kadima E , Abrams W , Segolodi T , Hader S , Lockman S , Moore J . J Acquir Immune Defic Syndr 2022 91 (1) 9-16 BACKGROUND: and Setting: The Botswana Combination Prevention Project (BCPP) 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: BCPP was a community-randomized controlled trial conducted in 30 rural/peri-urban 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 27,517py, 195 (women,79%) of 18,597 became HIV-infected (0.71/100py). Women had a higher IR (1.01/100py; 95% CI, 0.99 to 1.02) than men (0.34/100py; 95% CI, 0.33 to 0.35). The highest IRs were among women aged 16-24 years (1.87/100py) and men aged 25-34 years (0.56/100py). The lowest IRs were among those aged 35-64 years (women,0.41/100py; men,0.20/100py). Hazard of incident infection was highest among women aged 16-24 (HR=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 UNAIDS 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 (PrEP), DREAMS] to achieve epidemic control in this subpopulation and increased efforts with men with undiagnosed HIV. |
Health impact and cost-effectiveness of HIV testing, linkage, and early antiretroviral treatment in the Botswana Combination Prevention Project
Resch SC , Foote JHA , Wirth KE , Lasry A , Scott JA , Moore J , Shebl FM , Gaolathe T , Feser MK , Lebelonyane R , Hyle EP , Mmalane MO , Bachanas P , Yu L , Makhema JM , Holme MP , Essex M , Alwano MG , Lockman S , Freedberg KA . J Acquir Immune Defic Syndr 2022 90 (4) 399-407 BACKGROUND: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision (VMMC) referrals increased coverage and decreased incidence over ∼29 months follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population. SETTING: Rural and peri-urban communities in Botswana. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model to estimate lifetime health impact and cost of 1) earlier ART initiation, and 2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio (ICER, US$/QALY) for CP vs. standard of care. RESULTS: In CP, 1,418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9,200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an ICER of $79 per QALY. CONCLUSIONS: Enhanced HIV testing, linkage, and early ART initiation improves life expectancy, reduces transmission, and can be cost-effective or cost-saving in settings like Botswana. |
Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/ Ya Tsie trial.
Magosi LE , Zhang Y , Golubchik T , DeGruttola V , TchetgenTchetgen E , Novitsky V , Moore J , Bachanas P , Segolodi T , Lebelonyane R , PretoriusHolme M , Moyo S , Makhema J , Lockman S , Fraser C , Essex MM , Lipsitch M . Elife 2022 11 Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. Methods: To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana. We sequenced HIV viral whole genomes from 5,114 trial participants among the 30 trial communities. Results: Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 - 56.7] versus 3% [0.1 - 27.3]) than at baseline (7% [1.5 - 25.3] versus 5% [0.9 - 22.9]) compatible with a benefit from treatment-as-prevention. Conclusion: Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies. Funding: This study was supported by the National Institute of General Medical Sciences (U54GM088558); the Fogarty International Center (FIC) of the U.S. National Institutes of Health (D43 TW009610); and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) (Cooperative agreements U01 GH000447 and U2G GH001911). |
HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana.
Bareng OT , Moyo S , Zahralban-Steele M , Maruapula D , Ditlhako T , Mokaleng B , Mokgethi P , Choga WT , Moraka NO , Pretorius-Holme M , Mine MO , Raizes E , Molebatsi K , Motswaledi MS , Gobe I , Mohammed T , Gaolathe T , Shapiro R , Mmalane M , Makhema JM , Lockman S , Essex M , Novitsky V , Gaseitsiwe S . J Antimicrob Chemother 2022 77 (5) 1385-1395 OBJECTIVES: To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project. METHODS: A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL. RESULTS: Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group. CONCLUSIONS: A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring. |
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
Lebelonyane R , Bachanas P , Block L , Ussery F , Alwano MG , Marukutira T , El Halabi S , Roland M , Abrams W , Ussery G , Miller JA , Lockman S , Gaolathe T , Holme MP , Hader S , Mills LA , Wirth K , Bock N , Moore J . PLoS One 2021 16 (8) e0255227 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. |
Nanoparticles as a Tool in Neuro-Oncology Theranostics
Klein AL , Nugent G , Cavendish J , Geldenhuys WJ , Sriram K , Porter D , Fladeland R , Lockman PR , Sherman JH . Pharmaceutics 2021 13 (7) The rapid growth of nanotechnology and the development of novel nanomaterials with unique physicochemical characteristics provides potential for the utility of nanomaterials in theranostics, including neuroimaging, for identifying neurodegenerative changes or central nervous system malignancy. Here we present a systematic and thorough review of the current evidence pertaining to the imaging characteristics of various nanomaterials, their associated toxicity profiles, and mechanisms for enhancing tropism in an effort to demonstrate the utility of nanoparticles as an imaging tool in neuro-oncology. Particular attention is given to carbon-based and metal oxide nanoparticles and their theranostic utility in MRI, CT, photoacoustic imaging, PET imaging, fluorescent and NIR fluorescent imaging, and SPECT imaging. |
Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.
Bachanas P , Alwano MG , Lebelonyane R , Block L , Behel S , Raizes E , Ussery G , Wang H , Ussery F , Pretorius Holme M , Sexton C , Pals S , Lasry A , Del Castillo L , Hader S , Lockman S , Bock N , Moore J . PLoS One 2021 16 (4) e0250211 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. |
Early use of the palliative approach to improve patient outcomes in HIV disease: Insights and findings from the Care and Support Access (CASA) Study 2013-2019
Alexander CS , Raveis VH , Karus D , Carrero-Tagle M , Lee MC , Pappas G , Lockman K , Brotemarkle R , Memiah P , Mulasi I , Hossain BM , Welsh C , Henley Y , Piet L , N'Diaye S , Murray R , Haltiwanger D , Smith CR , Flynn C , Redfield R , Silva CL , Amoroso A , Selwyn P . Am J Hosp Palliat Care 2020 38 (4) 332-339 Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort. |
Implementation of universal HIV testing and treatment to reduce HIV incidence in Botswana: the Ya Tsie Study
Lockman S , Holme MP , Makhema J , Bachanas P , Moore J , Wirth KE , Lebelonyane R , Essex M . Curr HIV/AIDS Rep 2020 17 (5) 478-486 PURPOSE OF REVIEW: Antiretroviral treatment (ART) can dramatically reduce the risk of HIV transmission, but the feasibility of scaling up HIV testing, linkage and treatment to very high population levels, and its impact on population HIV incidence, were unknown. We review key findings from a community-randomized trial in which we evaluated the impact of "universal test and treat" (UTT) on population HIV incidence in Botswana, a resource-constrained country with both high HIV prevalence and high ART coverage before study inception. RECENT FINDINGS: We conducted a community-randomized trial (the "Ya Tsie" trial or Botswana Combination Prevention Project (BCPP)) in 30 villages in Botswana from 2013 to 2018, with the goal of determining whether a combination of prevention interventions-with a focus on universal HIV testing and treatment-would reduce population-level HIV incidence. The intervention included universal HIV testing (home-based and mobile), active linkage to HIV care and treatment with patient tracing for persons not linking, universal ART coverage, rapid ART start (at the first clinic visit), and enhanced male circumcision services. Botswana had very high HIV diagnosis, treatment, and viral suppression levels (approaching the UNAIDS "90-90-90" targets) prior to intervention roll-out. By study end, we were able to exceed the overall 95-95-95 coverage target of 86%: an estimated 88% of all persons living with HIV were on ART and had viral suppression in the Ya Tsie intervention arm. In addition, annual HIV incidence was 30% lower in the intervention arm as compared with the control arm over a 29-month follow-up period. With universal HIV testing and relatively simple linkage activities, it was possible to achieve one of the highest reported population levels of HIV diagnosis, linkage to care, and viral suppression globally and to reduce population HIV incidence by about one-third over a short period of time (< 3 years). We were able to significantly increase population viral suppression and to decrease HIV incidence even in a resource-constrained setting with pre-existing very high testing and treatment coverage. Universal community-based HIV testing and tracing of individuals through the HIV care cascade were key intervention components. |
Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after study
Lebelonyane R , Bachanas P , Block L , Ussery F , Abrams W , Roland M , Theu J , Kapanda M , Matambo S , Lockman S , Gaolathe T , Makhema J , Moore J , Jarvis JN . Lancet HIV 2020 7 (8) e545-e553 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
Lebelonyane R , Mills LA , Mogorosi C , Ussery F , Marukutira T , Theu J , Kapanda M , Matambo S , Block L , Raizes E , Makhema J , Lockman S , Bachanas P , Moore J , Jarvis JN . AIDS 2020 34 (15) 2223-2230 OBJECTIVE(S): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 ≤200 cells/μL) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. DESIGN: A sub-analysis 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 (ART) 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 ≤200 cells/μL vs. > 200 cells/μL). RESULTS: Overall, 17.2% (430/2,499; 95% confidence interval [CI] 15.7-18.8%) of study participants had advanced HIV disease (CD4 ≤200 cells/μL) at time of clinic linkage. Men were significantly more likely to present with CD4 ≤200 cells/μL than women (23.7% versus 13.4%, adjusted odds ratio [aOR] 1.9, 95% CI 1.5-2.3). The risk of advanced HIV disease increased with increasing age (aOR 2.2, 95% CI 1.4-3.2 > 35 years versus < 25 years). Patients with CD4 ≤200 cells/μL had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). CONCLUSIONS: Advanced HIV disease due to late presentation to or disengagement from ART 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. |
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
Wirth KE , Gaolathe T , Pretorius Holme M , Mmalane M , Kadima E , Chakalisa U , Manyake K , Matildah Mbikiwa A , Simon SV , Letlhogile R , Mukokomani K , van Widenfelt E , Moyo S , Bennett K , Leidner J , Powis KM , Lebelonyane R , Alwano MG , Jarvis J , Dryden-Peterson SL , Kgathi C , Moore J , Bachanas P , Raizes E , Abrams W , Block L , Sento B , Novitsky V , El-Halabi S , Marukutira T , Mills LA , Sexton C , Pals S , Shapiro RL , Wang R , Lei Q , DeGruttola V , Makhema J , Essex M , Lockman S , Tchetgen Tchetgen EJ . Lancet HIV 2020 7 (6) e422-e433 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. |
What do the Universal Test and Treat trials tell us about the path to HIV epidemic control
Havlir D , Lockman S , Ayles H , Larmarange J , Chamie G , Gaolathe T , Iwuji C , Fidler S , Kamya M , Floyd S , Moore J , Hayes R , Petersen M , Dabis F . J Int AIDS Soc 2020 23 (2) e25455 INTRODUCTION: Achieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign. DISCUSSION: These three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured. CONCLUSIONS: These trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets. |
Increasing knowledge of HIV status in a country with high HIV testing coverage: Results from the Botswana Combination Prevention Project
Alwano MG , Bachanas P , Block L , Roland M , Sento B , Behel S , Lebelonyane R , Wirth K , Ussery F , Bapati W , Motswere-Chirwa C , Abrams W , Ussery G , Miller JA , Bile E , Fonjungo P , Kgwadu A , Holme MP , Del Castillo L , Gaolathe T , Leme K , Majingo N , Lockman S , Makhema J , Bock N , Moore J . PLoS One 2019 14 (11) e0225076 INTRODUCTION: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. METHODS: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. RESULTS: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16-24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. CONCLUSIONS: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely. |
Self-reported risky sexual practices among adolescents and young adults in Botswana
Chakalisa U , Wirth K , Bennett K , Kadima E , Manyake K , Gaolathe T , Bachanas P , Marukutira T , Lebelonyane R , Dryden-Peterson S , Butler L , Mmalane M , Makhema J , Roland ME , Pretorius-Holme M , Essex M , Lockman S , Powis KM . South Afr J HIV Med 2019 20 (1) 899 Background: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. Objectives: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities. Methods: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. Results: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44-1.80), intergenerational sex (PR 9.00; 95% CI 5.84-13.88) and transactional sex (PR 3.46; 95% CI 2.07-5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41-0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45-0.76) or having >/= two partners in the last 12 months (PR 0.65; 95% CI 0.57-0.74). Conclusions: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming. |
Barriers and facilitators to linkage to care and ART initiation in the setting of high ART coverage in Botswana
Kebaabetswe P , Manyake K , Kadima E , Auletta-Young C , Chakalisa U , Sekoto T , Dintwa OM , Mmalane M , Makhema J , Lebelonyane R , Bachanas P , Plank R , Gaolathe T , Lockman S , Holme MP . AIDS Care 2019 32 (6) 1-7 We conducted a qualitative study using focus groups and in-depth interviews to explore barriers to and facilitators of linkage-to-care and antiretroviral treatment (ART) initiation in Botswana. Participants were selected from communities receiving interventions through the Ya Tsie Study. Fifteen healthcare providers and 49 HIV-positive individuals participated. HIV-positive participants identified barriers including stigma, discrimination and overcrowded clinics, and negative staff attitudes; personal factors, such as a lack of acceptance of one's HIV status, non-disclosure, and gender differences; along with lack of social/family support, and certain religious beliefs. Healthcare providers cited delayed test results, poverty, and transport difficulties as additional barriers. Major facilitators were support from healthcare providers, including home visits, social support, and knowing the benefits of ART. Participants were highly supportive of universal ART as a personal health measure. Our results highlighted a persistent structural health facility barrier: HIV-positive patients expressed strong discontent with HIV care/treatment being delivered differently than routine healthcare, feeling inconvenienced and stigmatized by separately designated locations and days of service. This barrier was particularly problematic for highly mobile persons. Addressing this structural barrier, which persists even in the context of high ART uptake, could bring gains in willingness to initiate ART and improved adherence in Botswana and elsewhere. |
Universal testing, expanded treatment, and incidence of HIV infection in Botswana
Makhema J , Wirth KE , Pretorius Holme M , Gaolathe T , Mmalane M , Kadima E , Chakalisa U , Bennett K , Leidner J , Manyake K , Mbikiwa AM , Simon SV , Letlhogile R , Mukokomani K , van Widenfelt E , Moyo S , Lebelonyane R , Alwano MG , Powis KM , Dryden-Peterson SL , Kgathi C , Novitsky V , Moore J , Bachanas P , Abrams W , Block L , El-Halabi S , Marukutira T , Mills LA , Sexton C , Raizes E , Gaseitsiwe S , Bussmann H , Okui L , John O , Shapiro RL , Pals S , Michael H , Roland M , DeGruttola V , Lei Q , Wang R , Tchetgen Tchetgen E , Essex M , Lockman S . N Engl J Med 2019 381 (3) 230-242 BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.). |
Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana
Moyo S , Gaseitsiwe S , Zahralban-Steele M , Maruapula D , Nkhisang T , Mokaleng B , Mohammed T , Ditlhako TR , Bareng OT , Mokgethi TP , van Widenfelt E , Pretorius-Holme M , Mine MO , Raizes E , Yankinda EK , Wirth KE , Gaolathe T , Makhema JM , Lockman S , Essex M , Novitsky V . AIDS 2019 33 (6) 1073-1082 BACKGROUND: Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations. METHODS: Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations. A threshold of 2% was used for hypermutation adjustment. Viral suppression was considered at HIV-1 RNA load </=400 copies/ml. RESULTS: Among 4973 participants with HIV-1C sequences, ART data were available for 4927 (99%) including 3858 (78%) on ART. Among those on ART, 3435 had viral load data and 3297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI-associated and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval [CI] 1.0-2.5%) and 2.9% (95% CI 2.0-4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI-associated and NNRTI-associated drug resistance mutations in 16% (95% CI 10-25%) and 33% (95% CI 25-42%), respectively. CONCLUSION: We found a low prevalence of NRTI-associated and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%. |
Cross-sectional estimates revealed high HIV incidence in Botswana rural communities in the era of successful ART scale-up in 2013-2015
Moyo S , Gaseitsiwe S , Mohammed T , Pretorius Holme M , Wang R , Kotokwe KP , Boleo C , Mupfumi L , Yankinda EK , Chakalisa U , van Widenfelt E , Gaolathe T , Mmalane MO , Dryden-Peterson S , Mine M , Lebelonyane R , Bennett K , Leidner J , Wirth KE , Tchetgen Tchetgen E , Powis K , Moore J , Clarke WA , Lockman S , Makhema JM , Essex M , Novitsky V . PLoS One 2018 13 (10) e0204840 BACKGROUND: Botswana is close to reaching the UNAIDS "90-90-90" HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage. METHODS: We used a cross-sectional approach to assessing HIV incidence. A random, population-based sample of adults age 16-64 years was enrolled in 30 rural and peri-urban communities as part of the Botswana Combination Prevention Project (BCPP), from October 2013 -November 2015. Data and samples from the baseline household survey were used to estimate cross-sectional HIV incidence, following an algorithm that combined Limiting-Antigen Avidity Assay (LAg-Avidity EIA), ART status (documented or by testing ARV drugs in plasma) and HIV-1 RNA load. The LAg-Avidity EIA cut-off normalized optical density (ODn) was set at 1.5. The HIV-1 RNA cut-off was set at 400 copies/mL. For estimation purposes, the Mean Duration of Recent Infection was 130 days and the False Recent Rate (FRR) was evaluated at values of either 0 or 0.39%. RESULTS: Among 12,610 individuals participating in the baseline household survey, HIV status was available for 12,570 participants and 3,596 of them were HIV positive. LAg-Avidity EIA data was generated for 3,581 (99.6%) of HIV-positive participants. Of 326 participants with ODn </=1.5, 278 individuals were receiving ART verified through documentation and were considered to represent longstanding HIV infections. Among the remaining 48 participants who reported no use of ART, 14 had an HIV-1 RNA load </=400 copies/mL (including 3 participants with ARVs in plasma) and were excluded, as potential elite/viremic controllers or undisclosed ART. Thus, 34 LAg-Avidity-EIA-recent, ARV-naive individuals with detectable HIV-1 RNA (>400 copies/mL) were classified as individuals with recent HIV infections. The annualized HIV incidence among 16-64 year old adults was estimated at 1.06% (95% CI 0.68-1.45%) with zero FRR, and at 0.64% (95% CI 0.24-1.04%) using a previously defined FRR of 0.39%. Within a subset of younger individuals 16-49 years old, the annualized HIV incidence was estimated at 1.29% (95% CI 0.82-1.77%) with zero FRR, and at 0.90% (95% CI 0.42-1.38%) with FRR set to 0.39%. CONCLUSIONS: Using a cross-sectional estimate of HIV incidence from 2013-2015, we found that at the time of near achievement of the UNAIDS 90-90-90 targets, ~1% of adults (age 16-64 years) in Botswana's rural and peri-urban communities became HIV infected annually. |
Lack of virological suppression among young HIV-positive adults in Botswana
Novitsky V , Gaolathe T , Mmalane M , Moyo S , Chakalisa U , Kadima Yankinda E , Marukutira T , Pretorius Holme M , Sekoto T , Gaseitsiwe S , Musonda R , van Widenfelt E , Powis KM , Khan N , Dryden-Peterson S , Bennett K , Wirth KE , Tchetgen Tchetgen E , Bachanas P , Mills LA , Lebelonyane R , Shenaaz EH , Makhema J , Lockman S , Essex M . J Acquir Immune Defic Syndr 2018 78 (5) 557-565 BACKGROUND: HIV-1 RNA load is the best biological predictor of HIV transmission and treatment response. The rate of virologic suppression among key sub-populations can guide HIV prevention programs. METHODS: The Botswana Combination Prevention Project performed a population-based household survey among adults in 30 communities in Botswana. Data collected included knowledge of HIV-positive status, ART coverage and virologic suppression (HIV-1 RNA </=400 copies/mL). Individuals aged 16-29 years were considered young adults. RESULTS: Among 552 young people living with HIV (PLHIV) enrolled with RNA load data and ART status available, 51% (n=279) had undetectable HIV-1 RNA, including 54% of young women and 32% of young men (gender PR: 0.53; 95% CI: 0.43-0.80; p<0.001). Compared with older adults (30-64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.65; 95%CI: 0.59-0.70; p<0.0001), including both men (PR: 0.43; 95%CI: 0.34-0.56; p<0.0001) and women (PR: 0.67; 95%CI: 0.62-0.74; p<0.0001). Among a subset of PLHIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95%CI: 0.90-0.95; p=<0.0001). Analysis of the care continuum revealed that inferior HIV diagnosis and sub-optimal linkage to care are the primary reasons for low virologic suppression among young adults. CONCLUSIONS: Young adults in Botswana are significantly less likely to have undetectable HIV-1 RNA load compared with older adults. In the era of broad scale-up of ART, interventions able to diagnose young adults living with HIV and link them to effective therapy are urgently needed. |
Undisclosed antiretroviral drug use in Botswana: implication for national estimates
Moyo S , Gaseitsiwe S , Powis KM , Pretorius Holme M , Mohammed T , Zahralban-Steele M , Yankinde EK , Maphorisa C , Abrams W , Lebelonyane R , Manyake K , Sekoto T , Mmalane M , Gaolathe T , Wirth KE , Makhema J , Lockman S , Clarke W , Essex M , Novitsky V . AIDS 2018 32 (11) 1543-1546 Among 3596 HIV-positive participants enrolled in Botswana Combination Prevention Project who self-reported no prior antiretroviral (ARV) therapy use and were tested for viral load (n = 951; 27% of all participants), 136 (14%) had HIV-1 RNA less than 400 copies/ml. ARV drugs were detected in 52 (39%) of 134 participants tested. Adjusting for undisclosed ARV use increased the overall estimate of virally suppressed individuals on ARV therapy by 1.4% from 70.2 to 71.6%. |
A tale of two countries: progress towards UNAIDS 90-90-90 targets in Botswana and Australia
Marukutira T , Stoove M , Lockman S , Mills LA , Gaolathe T , Lebelonyane R , Jarvis JN , Kelly SL , Wilson DP , Luchters S , Crowe SM , Hellard M . J Int AIDS Soc 2018 21 (3) 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. |
Comparative assessment of five trials of universal HIV testing and treatment in sub-Saharan Africa
Perriat D , Balzer L , Hayes R , Lockman S , Walsh F , Ayles H , Floyd S , Havlir D , Kamya M , Lebelonyane R , Mills LA , Okello V , Petersen M , Pillay D , Sabapathy K , Wirth K , Orne-Gliemann J , Dabis F . J Int AIDS Soc 2018 21 (1) DESIGN: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials. METHODS: We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations. RESULTS: All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation. CONCLUSIONS: We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally. |
Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies
Arikawa S , Rollins N , Jourdain G , Humphrey J , Kourtis AP , Hoffman I , Essex M , Farley T , Coovadia HM , Gray G , Kuhn L , Shapiro R , Leroy V , Bollinger RC , Onyango-Makumbi C , Lockman S , Marquez C , Doherty T , Dabis F , Mandelbrot L , Le Coeur S , Rolland M , Joly P , Newell ML , Becquet R . Clin Infect Dis 2017 66 (11) 1668-1677 Background: Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children. Results: Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion: Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates. |
High HIV-1 RNA among newly diagnosed people in Botswana
Novitsky V , Prague M , Moyo S , Gaolathe T , Mmalane M , Kadima Yankinda E , Chakalisa U , Lebelonyane R , Khan N , Powis KM , Widenfelt E , Gaseitsiwe S , Dryden-Peterson SL , Pretorius Holme M , De Gruttola V , Bachanas P , Makhema J , Lockman S , Essex M . AIDS Res Hum Retroviruses 2017 34 (3) 300-306 OBJECTIVE: HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to determine whether HIV-1 RNA level was associated with prior knowledge of HIV status among treatment-naive HIV-infected individuals in Botswana, a country with high rates of antiretroviral treatment (ART) coverage. This information may be helpful in targeting HIV diagnosis and treatment efforts in similar high-HIV-prevalence settings. DESIGN: Population-based survey. METHODS: HIV-infected individuals were identified during a household survey performed in 30 communities across Botswana. ART-naive persons with detectable HIV-1 RNA (>400 copies/mL) were divided into two groups, newly diagnosed and individuals tested in the past who knew about their HIV infection at the time of household visit but had not taken ART. Levels of HIV-1 RNA were compared between groups, overall and by age and gender. RESULTS: Among 815 HIV-infected ART-naive persons with detectable virus, newly diagnosed individuals had higher levels of HIV-1 RNA (n=490, median HIV-1 RNA 4.35, IQR 3.79-4.91 log10 copies/mL) than those who knew about their HIV-positive status (n=325, median HIV-1 RNA 4.10, IQR 3.55-4.68 log10 copies/mL; p-values <0.001, but p-value =0.011 after adjusting for age and gender). A non-significant trend for higher HIV-1 RNA was found among newly diagnosed men aged 30 years or older (median HIV-1 RNA 4.58, IQR 4.07-5.02 log10 copies/mL vs. 4.17, 3.61-4.71 log10 copies/mL). CONCLUSIONS: Newly diagnosed individuals have elevated levels of HIV-1 RNA. This study highlights the need for early diagnosis and treatment of HIV infection for purposes of HIV epidemic control, even in a setting with high ART coverage. |
Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1.
Balasubramanian R , Fowler MG , Dominguez K , Lockman S , Tookey PA , Huong NNG , Nesheim S , Hughes MD , Lallemant M , Tosswill J , Shaffer N , Sherman G , Palumbo P , Shapiro DE . AIDS 2017 31 (18) 2465-2474 OBJECTIVE: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. DESIGN: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). METHODS: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. RESULTS: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). CONCLUSION: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status. |
Physical, mental, and financial impacts from drought in two California counties, 2015
Barreau T , Conway D , Haught K , Jackson R , Kreutzer R , Lockman A , Minnick S , Roisman R , Rozell D , Smorodinsky S , Tafoya D , Wilken JA . Am J Public Health 2017 107 (5) e1-e8 OBJECTIVES: To evaluate health impacts of drought during the most severe drought in California's recorded history with a rapid assessment method. METHODS: We conducted Community Assessments for Public Health Emergency Response during October through November 2015 in Tulare County and Mariposa County to evaluate household water access, acute stressors, exacerbations of chronic diseases and behavioral health issues, and financial impacts. We evaluated pairwise associations by logistic regression with pooled data. RESULTS: By assessment area, households reported not having running water (3%-12%); impacts on finances (25%-39%), property (39%-54%), health (10%-20%), and peace of mind (33%-61%); worsening of a chronic disease (16%-46%); acute stress (8%-26%); and considering moving (14%-34%). Impacts on finances or property were each associated with impacts on health and peace of mind, and acute stress. CONCLUSIONS: Drought-impacted households might perceive physical and mental health effects and might experience financial or property impacts related to the drought. Public Health Implications. Local jurisdictions should consider implementing drought assistance programs, including behavioral health, and consider rapid assessments to inform public health action. (Am J Public Health. Published online ahead of print March 21, 2017: e1-e8. doi:10.2105/AJPH.2017.303695). |
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