Towards control of the global HIV epidemic: addressing the middle-90 challenge in the UNAIDS 90–90–90 target

In a Perspective, Collins Iwuji and Marie-Louise Newell discuss early findings from Richard Hayes and colleagues' PopART study on HIV testing and treatment.</p

HIV assessment and testing for hospital inpatients: still a weak link in the cascade

Since 2007, the World Health Organization has recommended that in countries with generalized HIV epidemics, HIV testing and counselling should be offered to all adults and adolescents seen in a health facility (1). This recommendation had been policy in Uganda since 2005 (2). However, evidence suggests that translation of this policy to practice in real-world settings has been patchy and that missed opportunities with HIV testing in the inpatient setting are still contributing to HIV related deaths (3,4)

Circulating resistance to first-line HIV drug regimens in sub-Saharan Africa: a sheep in wolf’s clothing?

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“It is better to die”: experiences of traditional health practitioners within the HIV treatment as prevention trial communities in rural South Africa (ANRS 12249 TasP trial)

The ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomized trial in rural South Africa uses a “test and treat” approach. Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial. A social science research agenda was nested within TasP with the aim of understanding the social, economic and contextual factors that affect individuals, households, communities and health systems with respect to TasP. Considering the rural nature of the trial setting, we sought to understand community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners (THPs). A qualitative study design was adopted using four repeat focus group discussions conducted with nine THPs, combined with community walks and photo-voice techniques, over a period of 18 months. A descriptive, interpretive and explanatory approach to analysis was adopted. Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically, home-based testing services were perceived as relatively successful in increasing access to HIV testing. A major gap observed by THPs was linkage to HIV clinics. Most of their clients, and some of the THPs themselves, found it difficult to use HIV clinics due to fear of labelling, stigma and discrimination, and the ensuing personal implications of unsolicited disclosure. On the one hand, a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics. On the other hand, THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals. Therefore, acceptability of the TasP test and treat approach by THPs is a major boost to the intervention, but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care, including partnerships with THPs themselves

Opportunities and challenges in HIV treatment as prevention research: results from the ANRS 12249 cluster-randomized trial and associated population cohort

Purpose of Review The ANRS 12249 treatment as prevention (TasP) trial investigated the impact of a universal test and treat (UTT) approach on reducing HIV incidence in one of the regions of the world most severely affected by the HIV epidemic—KwaZulu-Natal, South Africa. We summarize key findings from this trial as well as recent findings from controlled studies conducted in the linked population cohort quantifying the long-term effects of expanding ART on directly measured HIV incidence (2004–2017). Recent Findings The ANRS TasP trial did not—and could not—demonstrate a reduction in HIV incidence, because the offer of UTT in the intervention communities did not increase ART coverage and population viral suppression compared to the standard of care in the control communities. Ten controlled studies from the linked population cohort—including several quasi-experimental study designs—exploit heterogeneity in ART exposure to show a consistent and substantial impact of expanding provision of ART and population viral suppression on reduction in HIV incidence at the couple, household, community, and population levels. Summary In this setting, all of the evidence from large, population-based studies (inclusive of the ANRS TasP trial) is remarkably coherent and consistent—i.e., higher ART coverage and population viral suppression were repeatedly associated with clear, measurable decreases in HIV incidence. Thus, the expanded provision of ART has plausibly contributed in a major way toward the dramatic 43% decline in population-level HIV incidence in this typical rural African population. The outcome of the ANRS TasP trial constitutes a powerful null finding with important insights for overcoming implementation challenges in the population delivery of ART. This finding does not imply lack of ART effectiveness in blocking onward transmission of HIV nor its inability to reduce HIV incidence. Rather, it demonstrates that large increases in ART coverage over current levels will require health systems innovations to attract people living with HIV in early stages of the disease to participate in HIV treatment. Such innovations and new approaches are required for the true potential of UTT to be realized

Institutional responses to drought in a high HIV prevalence setting in rural South Africa

In 2015, South Africa experienced one of the worst (El Niño-induced) droughts in 35 years. This affected economic activities, individual and community livelihoods and wellbeing especially in rural communities in northern KwaZulu-Natal. Drought’s direct and indirect impacts on public health require urgent institutional responses, especially in South Africa’s stride to eliminate HIV as a public health threat by 2030 in line with the UNAIDS goals. This paper draws on qualitative data from interviews and policy documents to discuss how the devastating effect of the 2015 drought experience in the rural Hlabisa sub-district of uMkhanyakude, a high HIV prevalence area, imposes an imperative for more proactive institutional responses to drought and other climate-related events capable of derailing progress made in South Africa’s HIV/AIDS response. We found that drought had a negative impact on individual and community livelihoods and made it more difficult for people living with HIV to consistently engage with care due to economic losses from deaths of livestock, crop failure, food insecurity, time spent in search of appropriate water sources and forced relocations. It also affected government institutions and their interventions. Interviewed participants’ reflections on drought-related challenges, especially those related to institutional and coordination challenges, showed that although current policy frameworks are robust, their implementation has been stalled due to complex reporting systems, and inadequate interdepartmental collaboration and information sharing. We thus argue that to address the gaps in the institutional responses, there is a need for more inclusive systems of drought-relief implementation, in which government departments, especially at the provincial and district levels, work with national institutions to better share data/information about drought-risks in order to improve preparedness and implementation of effective mitigation measure

Antiretroviral therapy to prevent HIV acquisition in serodiscordant couples in a hyperendemic community in rural South Africa

Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI,. 07-.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed

Universal Test and Treat is not associated with sub-optimal antiretroviral therapy adherence in rural South Africa: the ANRS 12249 TasP trial

Introduction HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximise benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub-optimal adherence (<95%) during the first 12 months of ART. Methods A prospective cohort study nested within a two-arm cluster-randomised trial of universal test and treat implemented March 2012 - June 2016 to measure impact of ART on HIV incidence in rural KwaZulu-Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, 3 and 6 months, and six monthly thereafter. We pooled data from participants in both arms and used random-effects logistic regression models to examine the association between CD4 count at ART initiation and sub-optimal adherence, and assessed if adherence levels were associated with virological suppression. Results Among 900 individuals who initiated ART ≥ 12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4-46.4) and 71.7% were female. Adherence was sub-optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub-optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95-1.05, for VAS, and 1.03, 95%CI 0.99-1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p<0.001 for VAS; p=0.006 for PC). Conclusions We found no evidence that higher CD4 counts at ART initiation were associated with sub-optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long-term outcomes are needed

Retention in care trajectories of HIV-positive individuals participating in a universal test and treat programme in rural South Africa (ANRS 12249 TasP trial)

Objective: To study retention in care (RIC) trajectories and associated factors in patients eligible for antiretroviral treatment (ART) in a universal test-and-treat setting (TasP trial, South Africa, 2012-2016). Design: A cluster-randomized trial whereby individuals identified HIV-positive after home-based testing were invited to initiate ART immediately (intervention) or following national guidelines (control). Methods: Exiting care was defined as ≥3 months late for a clinic appointment, transferring elsewhere, or death. Group-Based Trajectory Modelling was performed to estimate RIC trajectories over 18 months and associated factors in 777 ART-eligible patients. Results: Four RIC trajectory groups were identified: i) group 1 “remained” in care (reference, n=554, 71.3%), ii) group 2 exited care then “returned” after (median [interquartile range]) 4 [3-9] months (n=40, 5.2%), iii) group 3 “exited care rapidly” (after 4 [4-6] months, n=98, 12.6%), iv) group 4 “exited care later” (after 11 [9-13] months, n=85, 10.9%). Group 2 patients were less likely to have initiated ART within 1 month and more likely to be male, young (350 cells/mm3. Group 3 patients were more likely to be women without social support, newly diagnosed, young, and less likely to have initiated ART within 1 month. Group 4 patients were more likely to be newly diagnosed and aged ≤39 years. Conclusions: High CD4 counts at care initiation were not associated with a higher risk of exiting care. Prompt ART initiation and special support for young and newly diagnosed HIV-patients are needed to maximize RIC

Access to HIV care in the context of universal test and treat: challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa

Introduction: We aimed to quantify and identify associated factors of linkage to HIV care following home-based HIV counselling and testing (HBHCT) in the ongoing ANRS 12249 treatment-as-prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. Methods: Individuals ]16 years were offered HBHCT; those who were identified HIV positive were referred to cluster-based TasP clinics and offered antiretroviral treatment (ART) immediately (five clusters) or according to national guidelines (five clusters). HIV care was also available in the local Department of Health (DoH) clinics. Linkage to HIV care was defined as TasP or DoH clinic attendance within three months of referral among adults not in HIV care at referral. Associated factors were identified using multivariable logistic regression adjusted for trial arm. Results: Overall, 1323 HIV-positive adults (72.9% women) not in HIV care at referral were included, of whom 36.9% (n488) linked to care B3 months of referral (similar by sex). In adjusted analyses (n1222), individuals who had never been in HIV care before referral were significantly less likely to link to care than those who had previously been in care (B33% vs. 42%, pB0.001). Linkage to care was lower in students (adjusted odds-ratio [aOR] 0.47; 95% confidence interval [CI] 0.240.92) than in employed adults, in adults who completed secondary school (aOR0.68; CI 0.490.96) or at least some secondary school (aOR0.59; CI 0.410.84) versus 5 primary school, in those who lived at 1 to 2 km (aOR0.58; CI 0.440.78) or 25 km from the nearest TasP clinic (aOR0.57; CI 0.410.77) versus B1 km, and in those who were referred to clinic after ]2 contacts (aOR0.75; CI 0.580.97) versus those referred at the first contact. Linkage to care was higher in adults who reported knowing an HIV-positive family member (aOR1.45; CI 1.121.86) versus not, and in those who said that they would take ART as soon as possible if they were diagnosed HIV positive (aOR2.16; CI 1.134.10) versus not. Conclusions: Fewer than 40% of HIV-positive adults not in care at referral were linked to HIV care within three months of HBHCT in the TasP trial. Achieving universal test and treat coverage will require innovative interventions to support linkage to HIV care