Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis.

BACKGROUND: Guidelines and implementation of tuberculosis preventive treatment (TPT) vary by age and HIV status. Specifically, TPT is strongly recommended for people living with HIV/AIDS (PLWHA) and household contacts younger than 5 years but only conditionally recommended for older contacts. Cost remains a major barrier to implementation. The aim of this study was to evaluate the cost-effectiveness of TPT for household contacts and PLWHA. METHODS: We developed a state-transition model to simulate short-course TPT for household contacts and PLWHA in 29 high-incidence countries based on data from previous studies and public databases. Our primary outcome was the incremental cost-effectiveness ratio, expressed as incremental discounted costs (2020 US$, including contact investigation costs) per incremental discounted disability-adjusted life year (DALY) averted, compared with a scenario without any TPT or contact investigation. We propagated uncertainty in all model parameters using probabilistic sensitivity analysis and also evaluated the sensitivity of results to the screening algorithm used to rule out active disease, the choice of TPT regimen, the modelling time horizon, assumptions about TPT coverage, antiretroviral therapy discontinuation, and secondary transmission. FINDINGS: Between 2023 and 2035, scaling up TPT prevented 0·9 (95% uncertainty interval 0·4-1·6) people from developing tuberculosis and 0·13 (0·05-0·27) tuberculosis deaths per 100 PLWHA, at an incremental cost of $15 (9-21) per PLWHA. For household contacts, TPT (with contact investigation) averted 1·1 (0·5-2·0) cases and 0·7 (0·4-1·0) deaths per 100 contacts, at a cost of $21 (17-25) per contact. Cost-effectiveness was most favourable for household contacts younger than 5 years ($22 per DALY averted) and contacts aged 5-14 years ($104 per DALY averted) but also fell within conservative cost-effectiveness thresholds in many countries for PLWHA ($722 per DALY averted) and adult contacts ($309 per DALY averted). Costs per DALY averted tended to be lower when compared with a scenario with contact investigation but no TPT. The cost-effectiveness of TPT was not substantially altered in sensitivity analyses, except that TPT was more favourable in analysis that considered a longer time horizon or included secondary transmission benefits. INTERPRETATION: In many high-incidence countries, short-course TPT is likely to be cost-effective for PLWHA and household contacts of all ages, regardless of whether contact investigation is already in place. Failing to implement tuberculosis contact investigation and TPT will incur a large burden of avertable illness and mortality in the next decade. FUNDING: Unitaid.

Key barriers and enablers associated with uptake and continuation of oral pre-exposure prophylaxis (PrEP) in the public sector in Zimbabwe: Qualitative perspectives of general population clients at high risk for HIV.

BACKGROUND: Understanding the perspectives and preferences of clients eligible for pre-exposure prophylaxis (PrEP) is essential to designing programs that meet clients' needs. To date, most PrEP programs in limited-resource settings have been implemented by partner organizations for specific target populations, but the government of Zimbabwe aims to make PrEP available to the broader population at substantial risk in public sector clinics. However, there is limited information on general population perspectives about PrEP in Zimbabwe. METHODS: A qualitative study was conducted to explore clients' motivation to take or decline PrEP and continue or discontinue PrEP. Through a PrEP pilot in one urban family planning clinic and one rural youth center in Zimbabwe, 150 HIV-negative clients screened as being at high risk of HIV and were offered PrEP between January and June 2018. Sixty semi-structured interviews were conducted with clients who agreed to follow-up (including 5 decliners, all from the rural youth center, and 55 accepters, with 42 from the rural youth center and 13 from the urban family planning clinic). Interviews were conducted after either the first or second PrEP follow-up appointment or after the client declined PrEP. Interviews were audio recorded, de-identified, transcribed, and coded thematically. RESULTS: PrEP uptake was driven by risk perception for HIV, and in many cases, that risk was introduced by the unsafe behavior or HIV-positive status of a partner. Among sero-discordant couples (SDCs), the desire to safely conceive a child was also cited as a factor in taking PrEP. Clients who opted for PrEP preferred it to other forms of HIV prevention. SDCs reported decreased condom use after PrEP initiation and in some cases were using PrEP while trying to conceive a child. After initiating PrEP, clients had more confidence in their sexual relationships and less stress associated with negotiating condom use. Family and partner support was critical to starting and continuing PrEP, but some clients stopped PrEP or missed appointments due to side effects or logistical challenges such as transportation. CONCLUSIONS: Results of this study can be used to provide operational guidance for national public sector roll-out of PrEP as part of combination HIV prevention in Zimbabwe. Based on feedback and experiences of clients, the training materials for health workers can be refined to ensure that health workers are prepared to counsel clients on the decision to start and/or continue PrEP and answer common client questions. Program advertisements should also be targeted with key messages that speak to client experiences. TRIAL REGISTRATION: Clinical Trial Registry Number: PACTR201710002651160.