The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study.

BACKGROUND: Although effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials. METHODS: We use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention. RESULTS: Delivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women. CONCLUSIONS: If efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.

A tale of two cascades: promoting a standardized tool for monitoring progress in HIV prevention.

INTRODUCTION: To achieve significant progress in global HIV prevention from 2020 onward, it is essential to ensure that appropriate programmes are being delivered with high quality and sufficient intensity and scale and then taken up by the people who most need and want them in order to have both individual and public health impact. Yet, currently, there is no standard way of assessing this. Available HIV prevention indicators do not provide a logical set of measures that combine to show reduction in HIV incidence and allow for comparison of success (or failure) of HIV prevention programmes and for monitoring progress in meeting global targets. To redress this, attention increasingly has turned to the prospects of devising an HIV prevention cascade, similar to the now-standard HIV treatment cascade; but this has proven to be a controversial enterprise, chiefly due to the complexity of primary prevention. DISCUSSION: We address a number of core issues attendant with devising prevention cascades, including: determining the population of interest and accounting for the variability and fluidity of HIV-related risk within it; the fact that there are multiple HIV prevention methods, and many people are exposed to a package of them, rather than a single method; and choosing the final step (outcome) in the cascade. We propose two unifying models of prevention cascades-one more appropriate for programme managers and monitors and the other for researchers and programme developers-and note their relationship. We also provide some considerations related to cascade data quality and improvement. CONCLUSIONS: The HIV prevention field has been grappling for years with the idea of developing a standardised way to regularly assess progress and to monitor and improve programmes accordingly. The cascade provides the potential to do this, but it is complicated and highly nuanced. We believe the two models proposed here reflect emerging consensus among the range of stakeholders who have been engaging in this discussion and who are dedicated to achieving global HIV prevention goals by ensuring the most appropriate and effective programmes and methods are supported.

The effect of 90-90-90 on HIV-1 incidence and mortality in eSwatini: a mathematical modelling study.

BACKGROUND: The rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030. METHODS: We used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15-49 by 2016, 2030, and 2050. FINDINGS: Between 2010 and 2016, status-quo ART scale-up among adults (aged 15-49 years) in eSwatini (from 34·0% in 2010 to 74·1% in 2016) reduced HIV incidence by 43·57% (95% credible interval 39·71 to 46·36) and HIV mortality by 56·17% (54·06 to 58·92) among individuals aged 15-49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1·09 (0·87 to 1·29) per 100 person-years, 1·42 (1·13 to 1·71) per 100 person-years among women and 0·79 (0·63 to 0·94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15-24 years (an additional 17·37% [7·33 to 26·12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35-49 years (1·99% [-5·09 to 7·74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection-an upper bound of plausible treatment effect-would reduce adult HIV incidence to 0·73 infections (0·55 to 0·92) per 100 person-years by 2030 and 0·46 (0·33 to 0·59) per 100 person-years by 2050. INTERPRETATION: Scale-up of ART over the last decade has already contributed to substantial reductions in HIV-1 incidence and mortality in eSwatini. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures. FUNDING: Global Good Fund and the Bill & Melinda Gates Foundation.

The importance of local epidemic conditions in monitoring progress towards HIV epidemic control in Kenya: a modelling study.

INTRODUCTION: Setting and monitoring progress towards targets for HIV control is critical in ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to local settings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor. METHODS: We use location-specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence. RESULTS: Considerable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equal to an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high-risk sub-populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as "condom use" or "pre-exposure prophylaxis coverage"). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long-term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent associations with long-term changes in incidence even in the largest generalized epidemics. CONCLUSIONS: Target setting should be appropriate for the local epidemic and what can feasibly be achieved. There is no one universally reliable indicator to predict future HIV incidence across settings. Thus, the signature of epidemic control must contain indications of success across a wide range of interventions and outcomes.

Documenting and explaining the HIV decline in east Zimbabwe: the Manicaland General Population Cohort.

PURPOSE: The Manicaland cohort was established to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic. The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral therapy (ART). PARTICIPANTS: General population open cohort located in 12 sites in Manicaland, east Zimbabwe, representing 4 major socioeconomic strata (small towns, agricultural estates, roadside settlements and subsistence farming areas). 9,109 of 11,453 (79.5%) eligible adults (men 17-54 years; women 15-44 years) were recruited in a phased household census between July 1998 and January 2000. Five rounds of follow-up of the prospective household census and the open cohort were conducted at 2-year or 3-year intervals between July 2001 and November 2013. Follow-up rates among surviving residents ranged between 77.0% (over 3 years) and 96.4% (2 years). FINDINGS TO DATE: HIV prevalence was 25.1% at baseline and had a substantial demographic impact with 10-fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas (towns) from 2.9% to 1.0%pa. HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners. HIV prevalence has since fallen to 15.8% and HIV incidence has also declined from 2.1% (1998-2003) to 0.63% (2009-2013) largely due to reduced sexual risk behaviour. HIV-associated mortality fell substantially after 2009 with increased availability of ART. FUTURE PLANS: We plan to extend the cohort to measure the effects on the epidemic of current and future HIV prevention and treatment programmes. Proposals for access to these data and for collaboration are welcome.

Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study.

BACKGROUND: The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes. METHODS: Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC). FINDINGS: In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3·1% to 6·9%. Of uninfected men, 85·3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27·5% to 56·6% and from 61·1% to 79·6%, respectively, with 30·4% of men tested self-reporting reduced sexual partner numbers and 12·8% reporting increased condom use. INTERPRETATION: Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation.

Trends in concurrency, polygyny, and multiple sex partnerships during a decade of declining HIV prevalence in eastern Zimbabwe.

BACKGROUND: Observed declines in the prevalence of human immunodeficiency virus (HIV) infection in Zimbabwe have been attributed to population-level reductions in sexual partnership numbers. However, it remains unknown whether certain types of sex partnerships were more important to this decline. Particular debate surrounds the epidemiologic importance of polygyny (the practice of having multiple wives). METHODS: We analyze changes in reported multiple partnerships, nonmarital concurrency, and polygyny in eastern Zimbabwe during a period of declining HIV prevalence, from 1998 to 2011. Trends are reported for adult men (age, 17-54 years) and women (age, 15-49 years) from 5 survey rounds of the Manicaland HIV/STD Prevention Project, a general-population open cohort study. RESULTS: At baseline, 34.2% of men reported multiple partnerships, 11.9% reported nonmarital concurrency, and 4.6% reported polygyny. Among women, 4.6% and 1.8% reported multiple partnerships and concurrency, respectively. All 3 partnership indicators declined by similar relative amounts (around 60%-70%) over the period. Polygyny accounted for around 25% of male concurrency. Compared with monogamously married men, polygynous men reported higher levels of subsequent divorce/separation (adjusted relative risk [RR], 2.92; 95% confidence interval [CI], 1.87-4.55) and casual sex partnerships (adjusted RR, 1.63; 95% CI, 1.41-1.88). CONCLUSIONS: No indicator clearly dominated declines in partnerships. Polygyny was surprisingly unstable and, in this population, should not be considered a safe form of concurrency.

Risk pathways for gonorrhea acquisition in sex workers: can we distinguish confounding from an exposure effect using a priori hypotheses?

The population distribution of sexually transmitted infections (STIs) varies broadly across settings. Although there have been many studies aiming to define subgroups at risk of infection that should be a target for prevention interventions by identifying risk factors, questions remain about how these risk factors interact, how their effects jointly influence the risk of acquisition, and their differential importance across populations. Theoretical frameworks describing the interrelationships among risk determinants are useful in directing both the design and analysis of research studies and interventions. In this article, we developed such a framework from a review looking at determinants of risk for STI acquisition, using gonorrhea as an index infection. We also propose an analysis strategy to interpret the associations found to be significant in uniform analyses of observational data. The framework and the hierarchical analysis strategy are of particular relevance in the understanding of risk formation and might prove useful in identifying determinants that are part of the causal pathway and therefore amenable to prevention strategies across populations.

Increasing adolescent HIV prevalence in Eastern Zimbabwe--evidence of long-term survivors of mother-to-child transmission?

Recent data from the Manicaland HIV/STD Prevention Project, a general-population open HIV cohort study, suggested that between 2004 and 2007 HIV prevalence amongst males aged 15-17 years in eastern Zimbabwe increased from 1.20% to 2.23%, and in females remained unchanged at 2.23% to 2.39%, while prevalence continued to decline in the rest of the adult population. We assess whether the more likely source of the increase in adolescent HIV prevalence is recent sexual HIV acquisition, or the aging of long-term survivors of perinatal HIV acquisition that occurred during the early growth of the epidemic. Using data collected between August 2006 and November 2008, we investigated associations between adolescent HIV and (1) maternal orphanhood and maternal HIV status, (2) reported sexual behaviour, and (3) reporting recurring sickness or chronic illness, suggesting infected adolescents might be in a late stage of HIV infection. HIV-infected adolescent males were more likely to be maternal orphans (RR = 2.97, p<0.001) and both HIV-infected adolescent males and females were more likely to be maternal orphans or have an HIV-infected mother (male RR = 1.83, p<0.001; female RR = 16.6, p<0.001). None of 22 HIV-infected adolescent males and only three of 23 HIV-infected females reported ever having had sex. HIV-infected adolescents were 60% more likely to report illness than HIV-infected young adults. Taken together, all three hypotheses suggest that recent increases in adolescent HIV prevalence in eastern Zimbabwe are more likely attributable to long-term survival of mother-to-child transmission rather than increases in risky sexual behaviour. HIV prevalence in adolescents and young adults cannot be used as a surrogate for recent HIV incidence, and health systems should prepare for increasing numbers of long-term infected adolescents.

Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial.

BACKGROUND: Cash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe. METHODS: We did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6-12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849. FINDINGS: 1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0-4 years with birth certificates had increased by 1·5% (95% CI -7·1 to 10·1) in the UCT group and by 16·4% (7·8-25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0-4 years with complete vaccination records was 3·1% (-3·8 to 9·9) greater in the UCT group and 1·8% (-5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6-12 years who attended school at least 80% of the time was 7·2% (0·8-13·7) higher in the UCT group and 7·6% (1·2-14·1) in the CCT group than in the control group. INTERPRETATION: Our results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region. FUNDING: Wellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children.

Understanding the modes of transmission model of new HIV infection and its use in prevention planning.

The modes of transmission model has been widely used to help decision-makers target measures for preventing human immunodeficiency virus (HIV) infection. The model estimates the number of new HIV infections that will be acquired over the ensuing year by individuals in identified risk groups in a given population using data on the size of the groups, the aggregate risk behaviour in each group, the current prevalence of HIV infection among the sexual or injecting drug partners of individuals in each group, and the probability of HIV transmission associated with different risk behaviours. The strength of the model is its simplicity, which enables data from a variety of sources to be synthesized, resulting in better characterization of HIV epidemics in some settings. However, concerns have been raised about the assumptions underlying the model structure, about limitations in the data available for deriving input parameters and about interpretation and communication of the model results. The aim of this review was to improve the use of the model by reassessing its paradigm, structure and data requirements. We identified key questions to be asked when conducting an analysis and when interpreting the model results and make recommendations for strengthening the model's application in the future.

Patterns of uptake of HIV testing in sub-Saharan Africa in the pre-treatment era.

OBJECTIVES: To compare nationally representative trends in self-reported uptake of HIV testing and receipt of results in selected countries prior to treatment scale-up. METHODS: Demographic and Health Survey (DHS) data from 13 countries in sub-Saharan Africa were used to describe the pattern of uptake of testing for HIV among sexually active participants. Univariate and multivariate logistic regression were used to analyse the associations between socio-demographic and behavioural characteristics and the uptake of testing. RESULTS: Knowledge of serostatus ranged from 2.2% among women in Guinea (2005) to 27.4% among women in Rwanda (2005). Despite varied levels of testing, univariate analysis showed the profile of testers to be remarkably similar across countries, with respect to socio-demographic characteristics such as area of residence and socio-economic status. HIV-positive participants were more likely to have tested and received their results than HIV-negative participants, with the exception of women in Senegal and men in Guinea. Adjusted analyses indicate that a secondary or higher level of education was a key determinant of testing, and awareness that treatment exists was independently positively associated with testing, once other characteristics were taken into account. CONCLUSION: This work provides a baseline for monitoring trends in testing and exploring changes in the profile of those who get tested after the introduction and scale-up of treatment.

Could better tolerated HIV drug regimens improve patient outcome?

OBJECTIVES: To quantify the performance of existing first-line and second-line combination antiretroviral therapy (cART) regimens on patient's clinical outcomes in the Netherlands using ATHENA data and to evaluate the potential for new drug regimens to improve patient's clinical outcomes using a data-based mathematical model. DESIGN AND METHODS: We analysed data from 3995 patients from the Dutch ATHENA national observational cohort between 2000 and 2010. We quantified the main drug-related reasons for switching from first-line and second-line cART, classified as toxicity, simplification/new medication becoming available, virological failure, or other reasons. We developed a deterministic model describing HIV infection and treatment in the Netherlands parameterized on the basis of these data. The model simulated how a new drug regimen, with either improved toxicity or virological failure profile, could impact on patient's clinical outcomes. RESULTS: The main reason for switching current first-line and second-line regimens was toxicity, accounting for around 50% of switching from first-line and from second-line cART. The model found that a new drug regimen with increased tolerability profile could have the highest potential impact on patient's outcomes, especially as a first-line treatment. A new first-line drug regimen with improved tolerability could increase the time patients spend on first-line cART, decrease their risk of switching from first-line cART and thus simplify patient management. CONCLUSION: New drug regimens with improved toxicity profiles could have the greatest impact on patient outcomes and simplify patient management in the Netherlands.

Treatment as prevention: translating efficacy trial results to population effectiveness.

PURPOSE OF REVIEW: The understanding that antiretroviral treatment prevents HIV transmission through suppression of viral load provides significant new opportunities in HIV prevention. However, knowledge of efficacy is only a first step to having an impact on the spread of HIV at a population level, the ultimate goal of all primary prevention modalities. This review explores what we know about treatment as prevention and how it could be used as a tool, as part of a combination approach, in the global response to HIV. RECENT FINDINGS: Efficacy data show that treatment as prevention works at high levels in trial conditions in stable serodiscordant couples; a finding that can reasonably be generalized to other populations at risk of transmitting the virus. Modelling shows that treatment as prevention should have an impact, but the extent of this depends primarily upon whether optimistic or pessimistic assumptions are made about the programmatic use of antiretrovirals (ARVs). SUMMARY: We describe research questions that need to be addressed in developing optimal programmatic public health treatment strategies including how best to target and implement the use of treatment as prevention, how to balance the needs of treatment for the individual patients' clinical benefit against population level benefits, and how to create programmes that are able to link people to and retain them in care.

Attitudes and acceptance of oral and parenteral HIV preexposure prophylaxis among potential user groups: a multinational study.

BACKGROUND: The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. METHODS AND FINDINGS: Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. CONCLUSIONS: Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development.

The clinical interpretation of viral blips in HIV patients receiving antiviral treatment: are we ready to infer poor adherence?

OBJECTIVES: Viral blips may be an indication of poor adherence to antiretroviral treatment. This article studies how the variations of the definitions of viral blips and that of the choice of sampling frame in studies investigating viral blips may contribute to the uncertainty of the associations between viral blips and possible causes. DESIGN: Mathematical modeling study allows us to study the impact of different sampling frames and different definitions of blips upon study results that are usually not feasible in clinical settings. METHODS: Using a previously published mathematical model, scenarios of different drug adherence levels and viral blips, with different sampling frames, were modeled. RESULTS: In the case of viral blips as a result of nonadherence to combinational antiretroviral therapy, rather than calculating the incidence of blips directly from the number of blips observed in a given period of time, it is better to report the proportion of observations in a given period of time that are ≥50 copies per milliliter. Therefore, as the denominator, the number of observations in a given period of time is important. However, the proportion of blips is not very informative on the drug adherence level. CONCLUSIONS: We should standardize definitions of viral blips and the choice of sampling frame and to report the proportion of observations of a given sampling frame in a given period of time that are ≥50 copies per milliliter, so that comparable data can be generated across different populations.