BackgroundIn 2014, the Joint United Nations Programme on HIV and AIDS (UNAIDS) and partners set the ‘90-90-90 targets’; aiming to diagnose 90% of all HIV positive people, provide antiretroviral therapy (ART) for 90% of those diagnosed and achieve viral suppression for 90% of those treated, by 2020. This results in 81% of all HIV positive people on treatment and 73% of all HIV positive people achieving viral suppression. We aimed to analyse how effective national HIV treatment programmes are at meeting these targets, using HIV care continuums or cascades.MethodsWe searched for HIV treatment cascades for 196 countries in published papers, conference presentations, UNAIDS databases and national reports. Cascades were constructed using reliable, generalisable, recent data from national, cross-sectional and longitudinal study cohorts. Data were collected for four stages; total HIV positive people, diagnosed, on treatment and virally suppressed. The cascades were categorised as complete (four stages) or partial (3 stages), and analysed for ‘break points’ defined as a drop >10% in coverage between consecutive 90-90-90 targets.Results69 country cascades were analysed (32 complete, 37 partial). Diagnosis (target one—90%) ranged from 87% (the Netherlands) to 11% (Yemen). Treatment coverage (target two—81% on ART) ranged from 71% (Switzerland) to 3% (Afghanistan). Viral suppression (target three—73% virally suppressed) was between 68% (Switzerland) and 7% (China).ConclusionsNo country analysed met the 90-90-90 targets. Diagnosis was the greatest break point globally, but the most frequent key break point for individual countries was providing ART to those diagnosed. Large disparities were identified between countries. Without commitment to standardised reporting methodologies, international comparisons are complex.

The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-Å crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity. The structure reveals an unusual RNA-binding mode in which two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact extensively with both RNA strands, but form no protein–protein contacts. CLIP-seq analysis revealed that APOBEC3H preferentially binds to sequences in the viral genome predicted to contain duplexes, a property that may facilitate both virion incorporation and catalytic activity.

Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8+ cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels and ultimately caused marked CD4+ T-cell depletion and AIDS-defining conditions. Transient treatment with anti-CD8 during acute HIV-1 infection caused rapid progression to AIDS, while untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.

IntroductionPatients on antiretroviral treatment with undetectable HIV RNA levels have a significantly lower risk of clinical disease progression and onward HIV transmission. This study aimed to estimate and compare the percentage of all HIV-positive people who are diagnosed, are linked to care, are taking antiretroviral treatment and have undetectable HIV RNA, in eight European and high-income countries: the United States, the United Kingdom, France, the Netherlands, Denmark, Australia, British Columbia (Canada) and Georgia.Materials and MethodsFor each country, the number of people in five key stages of the HIV treatment cascade was collected: 1. HIV infected, 2. Known to be HIV positive, 3. Linked to care, 4. Taking antiretroviral treatment, and 5. Having undetectable HIV RNA. Estimates were extracted from national reports [1–3], the UNAIDS database, conference proceedings [4] and peer-reviewed articles [5–7]. The quality of the estimates and reporting methods were assessed individually for each country, with selection criteria such as availability of nationwide database and routinely collected data. Treatment cascades were constructed using estimates from 2010 to 2012.ResultsAs shown in Table 1, the percentage of all infected people with undetectable HIV RNA ranged from 20% in Georgia to 59% in Denmark. Of the high-income countries, the United States has the lowest percentage of individuals with undetectable viral load (25% to median 52%), associated with the highest HIV incidence rate (15.30 per 100,000 to median 6.07 per 100,000). The pattern of the cascades differed between countries: in the United States, there is a fall from 66% to 33% (−33%) between linkage to care and start of antiretroviral treatment. However, in Georgia, the greatest loss in continuum was zat diagnosis, with 48% of undiagnosed HIV-positive individuals.ConclusionsThere are great disparities among European and high-income countries in the percentage of HIV-positive individual with undetectable HIV RNA. Furthermore, the treatment cascades show different key break points, underlying inequalities in HIV care between countries.