Journal Article Annotations
2016, 3rd Quarter
Annotations by John Grimaldi, MD and Mary Ann Cohen, MD, FAPM
Also of interest:
HIV Prevention Trials Network (HPTN) 052 trial provides strong evidence for ART as an effective strategy for preventing HIV transmission in serodifferent couples. Yet, because condom use was high among participants, it offers limited data about risk of transmission in discordant couples having condomless sex in which the infected partner is virologically suppressed on ART. To address this question, the PARTNER (Partners of People on ART – A New Evaluation of Risks) study followed 1166 serodifferent heterosexual and MSM couples in which the HIV-infected partner is taking suppressive ART and who are having condomless sex for a median of 1.3 years. The important finding of zero documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up) requires longer-term follow-up to more precisely estimate risk.
This prospective study of participants in the Veterans Aging Cohort study strengthens existing evidence supporting early identification and treatment of major depressive disorder (MDD) in HIV-infected individuals. Compared to HIV-infected participants without MDD at baseline, those with MDD were 30% more likely to experience incident acute myocardial infarction during the 5.8 year follow-up period after adjustment for demographic, CVD and HIV-specific risk factors. The authors discuss the possible role of biological, specifically systemic inflammation and coagulatory activation, behavioral, and social factors as well as HIV medications as possible mediators of this association. Future research regarding effective treatment of depression may identify a novel approach to preventing CVD and in turn reducing CVD morbidity and mortality in HIV-infected adults.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 initiative to end the AIDS epidemic by 2020 by achieving 73% virologic suppression worldwide will require a substantial investment of resources in economically limited areas. This study aims to justify the expenditure by delineating the return on investment by comparing the “current pace” strategy with the 90-90-90 initiative in South Africa. Using a microsimulation model, the differential effect of a wide range of clinical and epidemiologic scenarios are analyzed and compared with regard to HIV transmission, clinical outcomes, impact on maternal orphans and cost. Reaching 73% virologic suppression is plausible even though it will require best practices utilized in clinical trials. This analysis demonstrates that the 14% annual budget increase that will be needed over 10 years, for a total of $54 billion, “would yield extraordinary returns” and makes a “compelling cost-effective case.”
The finding: This randomized clinical trial involving hospitalized patients with poorly controlled HIV disease and active substance use used a 3 parallel-group repeated-measures design to test the effect of patient navigation with and without financial incentives relative to treatment as usual on viral suppression after 12 months. At 12 months, 6 months following the completion of the active intervention phase, the rates of viral suppression relative to nonsupression or death was a little more than one-third across the 3 groups with no significant difference between the patient navigation groups (with financial incentives versus without) or between either patient navigation group and treatment as usual. At 6 months, the navigation-plus-incentives group outperformed treatment-as-usual on several HIV-related secondary outcomes, including viral suppression, attendance at HIV care outpatient visits and use of HIV medications. There were no significant differences in secondary outcomes at 12 months by treatment group. With regard to substance-use-related secondary outcomes, there was no difference among groups in measures of drug use at 6 or 12 months. The authors conclude that “other approaches are needed to improve HIV outcomes in this vulnerable population.”
Strength and weaknesses: This study used a randomized design, a large number of patients at hospitals from 11 different geographic locations nationally with high HIV prevalence, and a treatment-as-usual comparison group to assess the effectiveness of 2 active interventions in suppressing viral load in patients with active drug use. Although previous research with individuals with drug use has suggested that patient navigation combined with financial incentives may improve engagement in substance-related treatment, this is the first study to examine the effect of combined interventions on viral suppression in an HIV population. The study presents several limitations. The type and variety of substance-related treatment services varied across study sites. The independent effect of financial incentives cannot be determined since there was no financial-incentives-only condition. Lastly, the secondary measures that concerned use of HIV care, substance-related treatment, and ART use were based on self-report.
Relevance: Identifying novel strategies for improving HIV medication adherence in the large percentage of HIV-infected individuals who remain nonsuppressed is a public health priority. This is especially important in HIV-infected individuals with active substance-related problems since drug use contributes to both poor HIV medication adherence as well as HIV transmission. The interventions tested in this study are relevant because they target simultaneously both HIV care-related and substance-use treatment-related behaviors. Although there was no significant difference in primary outcome among groups, the study highlighted areas for future study: the importance of social determinants of health-related behaviors and the need for availability of drug treatment interventions that are substance-specific. For example, in this study, stimulant use comprised the majority of subjects and was less likely than other substances to be associated with viral nonsuppression.
The finding: Using published data and expert opinion, this study explores the public health benefit and cost-effectiveness of three HIV prevention health delivery scenarios: 1) Preexposure prophylaxis (PrEP) alone, 2) PrEP with frequent screening, 3) PrEP with frequent screening and provision of antiretroviral therapy (ART) for individuals who become infected. A compartment model-based evaluation demonstrated that PrEP with frequent screening plus ART offered the highest value among interventions. However, the benefit of reducing HIV prevalence among people who inject drugs (PWID) by 14% by 2035 (from 6.5% to 5.6%) remains expensive with a cost of $44 billion over 20 years and $253,000 per quality-adjusted life-years gained. Calculated per year, this amount represents 9% of the domestic HIV/AIDS budget for 2015. Cost-effectiveness is impacted by cost of and adherence to PrEP as well as HIV transmission rates in affected populations. The intervention delivers greatest value in underserved PWID communities with high HIV prevalence and incidence.
Strength and weaknesses: This study fills an important gap in knowledge about the cost-effectiveness of PrEP in PWID relative to other less costly HIV prevention strategies. The empirically calibrated compartmental model allowed for comparison among subgroups of PWID and determination that value is greatest in PWID at highest risk for HIV transmission. However, the model is limited in its examination of PWID as one risk group and by not stratifying individuals according to substance injected. Thus frequency of injection, the effectiveness of opioid agonist therapy and sexual behavior are not accounted for. Additionally, recent changes in guidelines recommending early initiation of ART for all infected individuals while possibly resulting in higher HIV prevalence, will likely decrease transmission thus bias results in favor of PrEP.
Relevance: Despite the success of needle exchange programs and opioid agonist therapies in reducing HIV incidence in PWID, this group accounts for a disproportionate share of infected individuals. This study will inform healthcare policy regarding allocation of scarce resources among HIV prevention efforts. The high comorbidity between substance related and psychiatric disorders and the synergistic effects in HIV transmission argue for evaluation of cost and benefit of novel HIV prevention strategies.
The finding: This article presents the final results of the HIV Prevention Trials Network (HPTN) 052 trial. Rates of HIV transmission in serodiscordant couples that began antiretroviral therapy at study enrollment were compared with transmission rates in serodiscordant couples that delayed treatment initiation until participants’ CD4+ cell count fell below 250 cells per cubic millimeter or participants developed an AIDS-defining illness. In May 2011, four years after full study enrollment began, all delayed-treatment participants were offered ART when interim analysis revealed a 96% reduction in genetically-linked index-to-partner HIV-1 infections among couples in the early ART initiation group. By the prespecified conclusion of the study in May 2015, participants in the early ART initiation group had a 93% lower risk of linked partner infection compared to those who delayed treatment. There were no linked infections observed when index participants had stable suppressed viremia.
Strength and weaknesses: The study’s inclusion of 1763 index participants and randomized design strengthen previous findings from observational studies suggesting that effective ART therapy prevents HIV transmission. The use of multiple study locations worldwide makes results generalizable to most clinical settings. Participants were followed for a median of 5.5 years suggesting that the observed benefits of ART therapy are sustainable. Participants were mostly heterosexual couples thus limiting findings to this risk group. The relatively frequent study follow-up visits may not reflect real world clinical settings where patients may be seen only one to two times annually, thus further limiting generalizability of findings.
Relevance: In contrast to dramatic progress in HIV treatment and decline in morbidity and mortality, the incidence of new infections remains stubbornly high with over 2 million reported worldwide in 2014. This study lends optimism to prevention strategies based on expanded HIV testing and retention in care, a cornerstone of the global 90-90-90 initiative to end AIDS. The significant number of unlinked partner infections (transmission by someone other than the index partner) underscores the importance of combining additional prevention strategies. The well-documented association between poor ART adherence and mental health conditions such as depression, PTSD, and substance use disorders underscores the role of mental health providers in stemming new infections.