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Summary Background Global HIV programs continue to experience challenges achieving the high rates of HIV testing and treatment needed to optimize health and reduce transmission. Botswana represents a useful “demonstration case” in assessing the feasibility of achieving the new UNAIDS targets for 2020: 90% of all persons living with HIV knowing their status, 90% of these individuals receiving sustained antiretroviral treatment (ART), and 90% of those on ART having virologic suppression (“90–90–90”). Methods A population-based random sample of individuals was recruited and interviewed in 30 rural and peri-urban communities from October 2013 to November 2015 in Botswana as part of a large, ongoing PEPFAR-funded community-randomized trial designed to evaluate the impact of a combination prevention package on HIV incidence. A random sample of approximately 20% of households in each of these 30 communities was selected. Consenting household residents aged 16–64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in absence of documentation of positive HIV status. HIV-1 RNA testing was performed in all HIV-infected participants, regardless of treatment status. Findings Eighty-one percent of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12,610 participants surveyed, 3,596 (29%) were HIV infected; 2,995 (83·3%) of these individuals already knew their HIV status. Among those who knew their HIV status, 2,617 (87·4%) were currently receiving ART (this represented 95% of those eligible for ART by current Botswana national guidelines, and 73% of all HIV-infected persons). We obtained an HIV-1 RNA result in 99·7% of HIV-infected participants. Of the 2,609 individuals currently receiving ART with a viral load measurement, 2,517 (96·5%) had HIV-1 RNA ≤400 copies/mL. Overall, 70·2% of HIV-infected persons had virologic suppression, close to the UNAIDS target of 73%. Results of three sensitivity analyses to account for possible uncertainty due to non-participation and under-representation of urban areas, revealed somewhat lower, but nevertheless remarkably high 90–90–90 coverage. Interpretation Botswana, a resource-constrained setting with high HIV prevalence, appears to have achieved very high rates of HIV testing, treatment coverage, and virologic suppression for those on ART in this population-based survey, despite the Botswana ART initiation threshold of ≤350 cells/mm3. These findings provide evidence that the UNAIDS 90-90-90 targets, while ambitious, are achievable even in resource-constrained settings with high HIV burden. Funding The United States President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC).

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.

Often when jointly modeling longitudinal and survival data, we are interested in a multivariate longitudinal measure that may not fit well by linear models. To overcome this problem, we propose a joint longitudinal and survival model that has a nonparametric model for the longitudinal markers. We use cubic B-splines to specify the longitudinal model and a proportional hazards model to link the longitudinal measures to the hazard. To fit the model, we use a Markov chain Monte Carlo algorithm. We select the number of knots for the cubic B-spline model using the Conditional Predictive Ordinate (CPO) and the Deviance Information Criterion (DIC). The method and model selection approach are validated in a simulation. We apply this method to examine the link between viral load, CD4 count, and time to event in data from an AIDS clinical trial. The cubic B-spline model provides a good fit to the longitudinal data that could not be obtained with simple parametric models.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship.A question that has received a great deal of attention in evaluating new treatments in acquired immune deficiency syndrome (AIDS) clinical trials is that of finding a good surrogate marker for clinical progression. The identification of such a marker may be useful in assessing the efficacy of new therapies in a shorter period. The number of CD4-lymphocyte counts has been proposed as such a potential marker for human immune virus (HIV) trials because of its observed correlation with clinical outcome. But to evaluate the role of CD4 counts as a potential surrogate marker, we must better understand the relationship of clinical outcome to an individual's CD4 count history over time. The Cox proportional hazards regression model is used to study the relationship between CD4 counts as a time-dependent covariate and survival. Because the CD4 counts are measured only periodically and with substantial measurement error and biological variation, standard methods for estimating the parameters in the Cox model by maximizing the partial likelihood are no longer appropriate. Instead, we propose a two-stage approach. In the first stage the longitudinal CD4 count data are modeled using a repeated measures random components model. In the second stage methods for estimating the parameters in a Cox model when the data are assumed to be of this form are derived. We also considered methods to account for missing data patterns. These methods are applied to CD4 data from a randomized clinical trial of AIDS patients where half of the patients were randomized to receive Zidovudine (ZDV) and the other half were randomized to receive a placebo. Although a strong correlation between CD4 counts and survival is demonstrated, we also show that CD4 counts may not serve as a useful surrogate marker for assessing treatments for this population of patients.

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SYNOPSISObjectives. We assessed emergency department (ED) patient acceptance of opt-in, rapid human immunodeficiency virus (HIV) screening and identified demographic characteristics and HIV testing-history factors associated with acceptance of screening.Methods. A random sample of 18-to 55-year-old ED patients was offered rapid HIV screening. Patient acceptance or decline of screening and the reasons for acceptance or decline were analyzed with multivariable regression models. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for the logistic regression models.Results. Of the 2,099 participants, 39.3% accepted HIV screening. In a multinomial regression model, participants who were never married/not partnered, did not have private health insurance, and had 12 or fewer years of education were more likely to be screened due to concern about a possible HIV exposure. In a multivariable logistic regression model, the odds of accepting screening were greater among those who were younger than 40 years old (OR 1.61, 95% CI 1.32, 2.00), nonwhite (OR 1.28, 95% CI 1.04, 1.58), not married (OR 1.82, 95% CI 1.44, 2.28), lacking private health insurance (OR 1.40, 95% CI 1.13, 1.74), and who had 12 or fewer years of education (OR 1.43, 95% CI 1.16, 1.75). Despite use of a standardized protocol, patient acceptance of screening varied by which research assistant asked them to be screened. Patients not previously tested for HIV who were white, married, and 45 years or older and who had private health insurance were more likely to decline HIV screening.Conclusions. In an opt-in, universal, ED HIV screening program, patient acceptance of screening varied by demography, which indicates that the impact of such screening programs will not be universal. Future research will need to determine methods of increasing uptake of ED HIV screening that transcend patient demographic characteristics, HIV testing history, and motivation for testing.

ObjectivesCognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14+ enriched monocytes predicted cognitive impairment and brain injury.MethodsWe enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).ResultsThe mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.InterpretationReservoir burden of HIV DNA in monocyte-enriched (CD14+) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.