A qualitative study to explore daily versus on-demand oral pre-exposure prophylaxis (PrEP) in young people from South Africa, Uganda and Zimbabwe.

BACKGROUND: Adolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS. METHODS: Purposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP. RESULTS: Reasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP. CONCLUSIONS: Our study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection

The potential effect of pre-exposure prophylaxis (PrEP) roll-out on sexual-risk behaviour among adolescents and young people in East and southern Africa.

Pre-exposure prophylaxis (PrEP) is an HIV-prevention strategy recommended for those at high-risk of infection, including adolescents and young people (AYP). We explored how PrEP roll-out could influence sexual risk behaviour among AYP in East and southern Africa. Twenty-four group discussions and 60 in-depth interviews were conducted with AYP between 13 and 24 years old, recruited from community settings in Uganda, Zimbabwe and South Africa, from September 2018 to January 2019. Participants perceived that PrEP availability could change sexual behaviour among AYP, influencing: (1) condom use (increased preference for condomless sex, reduced need and decrease in use of condoms, relief from condom use discomfort, consistent condom use to curb sexually transmitted infections and pregnancies); (2) sexual activities (increase in sexual partners and sexual encounters, early sexual debut, sexual experimentation and peace of mind during risky sex, sexual violence and perversion); (3) HIV risk perception (neglect of other HIV prevention strategies, unknown sexual partner HIV status, adoption of PrEP). PrEP initiation may be associated with increased interest in sexual activities and risky sexual behaviour among AYP. PrEP should be included as part of a combination package of HIV prevention strategies for AYP with methods to prevent other sexually transmitted infections and unwanted pregnancies

Exploring Perceived Barriers and Facilitators of PrEP Uptake among Young People in Uganda, Zimbabwe, and South Africa.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people's perspectives toward PrEP. We conducted 24 group discussions and 60 in-depth interviews with males and females aged 13-24 years in Uganda, Zimbabwe, and South Africa between September 2018 and February 2019. We used the framework approach to generate themes and key concepts for analysis following the social ecological model. Young people expressed a willingness to use PrEP and identified potential barriers and facilitators of PrEP uptake. Barriers included factors at individual (fear of HIV, fear of side effects, and PrEP characteristics), interpersonal (parental influence, absence of a sexual partner), community (peer influence, social stigma), institutional (long waiting times at clinics, attitudes of health workers), and structural (cost of PrEP and mode of administration, accessibility concerns) levels. Facilitators included factors at individual (high HIV risk perception and preventing HIV/desire to remain HIV negative), interpersonal (peer influence, social support and care for PrEP uptake), community (adequate PrEP information and sensitization, evidence of PrEP efficacy and safety), institutional (convenient and responsive services, provision of appropriate and sufficiently resourced services), and structural (access and availability of PrEP, cost of PrEP) levels. The findings indicated that PrEP is an acceptable HIV prevention method. PrEP uptake is linked to personal and environmental factors that need to be considered for successful PrEP roll-out. Multi-level interventions needed to promote PrEP uptake should consider the social and structural drivers and focus on ways that can inspire PrEP uptake and limit the barriers

Individual and composite adverse pregnancy outcomes in a randomized trial on isoniazid preventative therapy among women living with human immunodeficiency virus

CITATION: Theron, G. et al. 2021. Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus. Clinical infectious diseases, 72(11):e784–e790. doi:10.1093/cid/ciaa1482The original publication is available at https://academic.oup.com/cid/Background: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. Methods: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. Results: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). Conclusions: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.https://academic.oup.com/cid/article/72/11/e784/5913421?login=truePublishers versio

A multi-country cross-sectional study to assess predictors of daily versus on-demand oral pre-exposure prophylaxis in youth from South Africa, Uganda and Zimbabwe.

INTRODUCTION: Sub-Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre-exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on-demand PrEP among AYP in South Africa, Uganda and Zimbabwe. METHODS: A cross-sectional survey was conducted in 2019 among 13- to 24-year olds, capturing socio-demographics, HIV risk behaviours and preferences for daily or on-demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age. RESULTS AND DISCUSSION: A total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17-22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on-demand PrEP with differences by site (p < 0.001), sex (p < 0.001) and age group (p = 0.003). On-demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18- to 24-year-olds vs. 47% in 13- to 15-year-olds). After adjusting for site, sex and age group, preference for on-demand PrEP decreased as sex frequency over the past month increased (p-trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on-demand PrEP (p-trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on-demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on-demand PrEP (p = 0.05). CONCLUSIONS: Our data show that AYP in four SSA communities prefer on-demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio-demographic differences and designed in conjunction with AYP

Symptoms of post-traumatic stress and associations with sexual behaviour and PrEP preferences among young people in South Africa, Uganda and Zimbabwe.

BACKGROUND: It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP. METHODS: Young people without HIV, aged 13-24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety. RESULTS: Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05-4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04-1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08-1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex. CONCLUSIONS: Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP

Prevention of HIV-1 transmission through breastfeeding: efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE): a randomized, open label, clinical trial.

CAPRISA, 2018.Abstract available in pdf

The potential effect of pre-exposure prophylaxis (PrEP) roll-out on sexualrisk behaviour among adolescents and young people in East and southern Africa

Pre-exposure prophylaxis (PrEP) is an HIV-prevention strategy recommended for those at high-risk of infection, including adolescents and young people (AYP). We explored how PrEP roll-out could influence sexual risk behaviour among AYP in East and southern Africa. Twenty-four group discussions and 60 in-depth interviews were conducted with AYP between 13 and 24 years old, recruited from community settings in Uganda, Zimbabwe and South Africa, from September 2018 to January 2019. Participants perceived that PrEP availability could change sexual behaviour among AYP, influencing: (1) condom use (increased preference for condomless sex, reduced need and decrease in use of condoms, relief from condom use discomfort, consistent condom use to curb sexually transmitted infections and pregnancies); (2) sexual activities (increase in sexual partners and sexual encounters, early sexual debut, sexual experimentation and peace of mind during risky sex, sexual violence and perversion); (3) HIV risk perception (neglect of other HIV prevention strategies, unknown sexual partner HIV status, adoption of PrEP). PrEP initiation may be associated with increased interest in sexual activities and risky sexual behaviour among AYP. PrEP should be included as part of a combination package of HIV prevention strategies for AYP with methods to prevent other sexually transmitted infections and unwanted pregnancies

Tenofovir concentrations in hair strongly predict virologic suppression in breastfeeding women.

BackgroundAntiretroviral treatment (ART) adherence is often suboptimal in the perinatal period. We measured hair tenofovir (TFV) concentrations as a metric of adherence in postpartum women to understand patterns and predictors of adherence throughout this critical period. In addition, we examined the association between hair TFV concentrations and virologic outcomes.MethodsBetween 12/2012 and 09/2016, hair samples were collected longitudinally from delivery through breastfeeding from women on ART in the Promoting Maternal and Infant Survival Everywhere study (NCT01061151) in sub-Saharan Africa. Hair TFV levels were measured using validated methods. Using generalized estimating equations, we estimated the association between hair TFV levels and virologic suppression (&lt;400 copies/ml) over time and assessed predictors of hair TFV levels.ResultsHair TFV levels were measured at 370 visits in 71 women from delivery through a median of 14 months (interquartile range 12-15) of breastfeeding. Levels ranged from below detection (0.002) to 1.067 ng/mg (geometric mean: 0.047). After at least 90 days on ART, 69 women had at least one viral load measured (median 5 measures, range 1-9); 18 (26%) experienced viremia at least once. Each doubling of TFV level more than doubled odds of concurrent virologic suppression [odds ratio 2.35, 95% confidence interval (CI): 1.44-3.84, P = 0.0006] and was associated with 1.43 times the odds of future suppression (95% CI: 0.75-2.73, P = 0.28). Relative to the first 3 months after delivery, hair levels were highest in months 6-12 (1.42-fold higher, 95% CI: 1.09-1.85, P = 0.01).ConclusionHair TFV levels strongly predicted concurrent virologic suppression among breastfeeding women. Objective adherence metrics can supplement virologic monitoring to optimize treatment outcomes in this important transition period