The HIV care cascade: models,measures and moving forward

Introduction

This article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.

Discussion

Questions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm³; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.

Conclusions

There is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.     

A Closer Look at Depression and Its Relationship to HIV Antiretroviral Adherence

Background  

Depression consistently predicts nonadherence to human immunodeficiency virus antiretroviral therapy, but which aspects of depression are most influential are unknown. Such knowledge could inform assessments of adherence readiness and the type of depression treatment to utilize.     

Combination antiretroviral therapy: health care providers confront emerging dilemmas

Recent editorials, conferences and clinical practice articles have discussed providers' concerns and practices regarding prescribing antiretroviral combination therapy for HIV. We aimed to deepen our understanding of these largely anecdotal reports and of the challenges facing experienced HIV clinicians today using qualitative methodology. Eight focus groups using a structured discussion guide were conducted. Data were analyzed by constant comparative analysis and open codes. Participants were a diverse group of 23 physicians, eight nurse practitioners and four physician assistants with significant experience providing care to HIV-seropositive patients in various San Francisco Bay Area health care settings. The following major themes emerged from the data: (1) providers expressed new optimism about helping HIV-seropositive patients live; (2) the main factors affecting providers' decisions about when to start combination therapy were the risks versus benefits of delaying therapy, and patients' health status, readiness to adhere and treatment preferences; (3) providers lacked resources to prepare patients to begin therapy and enhance adherence; (4) providers varied regarding assessment of adherence; and (5) providers were anxious about making decisions under conditions of uncertainty and were concerned about patient health outcomes. We concluded that experienced HIV clinicians were hopeful and excited about their increasing ability to help patients. This hope, however, was tempered by scepticism about the future and by their daily struggles to make treatment decisions under conditions of great uncertainty. Without access to adjunct supports or a multidisciplinary team, providers may not be able to optimally assess and enhance antiretroviral medication adherence.     

The relationship between HAART use and sexual activity among HIV-positive women of reproductive age in Brazil, South Africa, and Uganda

The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.     

Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive patients in sub-Saharan Africa

Background: Alcohol is heavily consumed in sub‐Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7‐, 14‐, and 21‐day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC‐AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC‐AUC of PEth versus any 21‐day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC‐AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.     

Socioeconomic status,access to triple therapy,and survival from HIV-disease since 1996

BACKGROUND: In the era before highly active antiretroviral therapy (HAART), socioeconomic status was associated with survival from HIV disease. We have explored socioeconomic status, access to triple therapy (HAART), and mortality in the context of a universal healthcare system. METHODS: We evaluated 1408 individuals who initiated double or triple therapy between 1 August 1996 and 31 December 1999, and were followed until 31 March 2000. Cumulative HIV-related mortality rates were estimated using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: In the overall Cox model, we found that adherence [risk ratio (RR) 0.83; per 10% increase], CD4 cell count (RR 1.53; per 100 cell decrease), and lower socioeconomic status (RR 2.19; high versus low), were associated with HIV-related mortality. However, socioeconomic status was not significant among patients prescribed triple therapy in a stratified analysis, or in a sub-analysis restricted to patients prescribed HAART in the initial regimen. When we investigated if inequitable access to HAART by socio-economic status could explain the discrepancy, we found that persons in the lower socio-economic strata were less likely to be prescribed triple therapy even after adjustment for clinical characteristics. CONCLUSION: In a universal healthcare system, socioeconomic status was strongly associated with HIV-related mortality. When we investigated possible explanations for this association, we found that individuals of lower socioeconomic status were less likely to receive triple therapy after adjustment for clinical characteristics. Our findings highlight the need for the monitoring of therapeutic guidelines to ensure equitable access, as treatment strategies are updated.     

In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques

The push-pull perfusion technique was used to measure GnRH release in unanesthetized female rhesus macaques (Macaca mulatta) and to examine the dynamic relationship between GnRH release and LH levels during the estrogen-induced LH surge. Each ovariectomized macaque was anesthetized and stereotaxically fitted with a push-pull cannula directed into the median eminence (ME). After at least 1 week of recovery, each animal received an estradiol benzoate (E2B) injection (42 micrograms/kg BW) or an oil (OIL) injection and underwent push-pull perfusion of the ME and blood sampling for at least 5 h between 28 and 56 h postinjection. Continuous 10-min push-pull perfusates were collected and prepared for GnRH RIA. Peripheral venous blood samples were obtained either hourly or every 10 min, and serum LH levels were determined by Leydig cell bioassay. GnRH release was detectable and pulsatile in areas in or adjacent to the ME or arcuate nucleus. In eight OIL monkeys, GnRH pulses were regular (approximately one pulse every 60 min) and of low amplitude (14.7 +/- 12.0 pg), with a mean GnRH release rate of 4.0 +/- 1.7 pg/10 min. In five E2B-treated monkeys, GnRH release during the rising phase of the LH surge occurred as an apparent burst of high amplitude GnRH pulses. The mean GnRH release rate (37.5 +/- 17.9 pg/10 min) and mean GnRH pulse amplitude (170.0 +/- 90.0 pg) during the 5 h before the peak LH level in E2B-treated monkeys were greater than OIL values (P less than 0.025, mean release; P less than 0.05, mean amplitude). Within individual E2B-treated monkeys, hourly mean GnRH release rates were significantly correlated with LH levels during the ascending limb of the LH surge (r = 0.75 +/- 0.11; P less than 0.025). We have concluded that an increase in GnRH neurosecretion occurs in E2B-treated monkeys and that it is associated with generation of the LH surge. On the basis of our observations, we hypothesize that the primate hypothalamus, through changes in GnRH secretion, actively participates in the E2B-induced LH surge.