HIV Nursing 2019; 19(3): 74–77 Conference Report Report from the 10th International AIDS Society Conference on HIV Science 21–24 July 2019 Mexico City, Mexico Shaun Watson Clinical Nurse Specialist (HIV Community), Chelsea and Westminster NHS Trust, London

Introduction surveillance sites in Botswana and an increased cover- age from 45% to 75% of all births, concluding that This year ’ s International AIDS Society (IAS) conference there is now a 0.3% prevalence of NTDs amongst ‘IAS19’ was held in Mexico City, a place that despite women taking dolutegravir at conception [2–4] . It was the danger warnings, was colourful, vibrant, friendly interesting to note that NTDs were noted in nine out and culturally fascinating. It’ s great to be here but this of 23 315 women without HIV, a 0.04% prevalence. is no jolly holiday as sessions start at 07:00 and end at What does this mean? Zash et al . concluded the session 20:30, for most of us it ’s a 45-minute taxi ride in as the with some clinical and policy recommendations based conference centre is at the edge of a very car-heavy city. on their fi ndings stating that there is a small potential IAS19 delivered a lot of new data with the long-awaited risk of NTDs compared with the larger potential benefi ts news on the potential link between dolutegravir and of dolutegravir use, there is a lack of data for most neural tube birth defects, new antiretroviral therapy other modern ARVs (except efavirenz, which interest- (ART), especially the simplifi cation of treatment regi- ingly was the initial focus of the Tsepamo). The overall mens with fewer drugs, fewer weekly doses, studies on prevalence of NTDs with dolutegravir is slightly higher implants and injectable drugs. There were also reports than all other exposure groups (0.20–0.27%). The World on real-world studies of pre-exposure prophylaxis (PrEP) Health Organization (WHO) strengthened this study implementation around the world, particularly how long by stating that everyone who starts ART in lower to people stay on PrEP, and advances towards both a middle income countries should start with a dolute- prevention vaccine and long-term remission of HIV. gravir-based regimen ‘the preferred fi rst-line regimen For this feedback article I ’ ll focus on the main headline for all adults and adolescents living with HIV’. grabbers and my favourite sessions. Weight gain Neural tube defects and ART Remember the days when we would positively encour- There were a few feedback sessions about ART and age patients to eat and gain weight, prescribing neural tube defects (NTDs), an exciting buzz rang anabolic steroids and supplements by the box load, around the conference centre as there has been a well those days have gone and weight gain is the closed press conference in the morning then a news cardiac and renal failure symptom of the year (expect to embargo until 14.30 when the speakers took to the hear lot about it). So here’ s the science from Michelle main stage. The alarm had been raised a few years Moorhouse from University of Witwatersrand, South ago when NTD was noticed in women living with HIV Africa, presenting for Hill et al , who discussed progres- who were taking dolutegravir in Botswana leading to sive rises in weight and clinical obesity for TAF/FTC/ their children having birth defects that affected the DTG and TDF/FTC/DTG versus TDF/FTC/EFV [5] She brain, spine or spinal cord, such as open and closed stated that dolutegravir (DTG) has been associated spina bifi da, encephalocele and anencephaly amongst with rises in body weight and clinical obesity (noted others. These NTDs occur in the fi rst month of preg- at CROI in 2019 by Bedimo R et al. [6] ; and Bourgi nancy, often before the woman knows she is pregnant et al. [7] ) which is more pronounced in people who are so for women of child bearing age this was a huge black and female. Weight gain after starting ART is a concern. First Fernanda Fernandez, from the Brazilian common ‘return to health’ symptom but substantial Ministry of Health, presented an abstract with the not weight gain, as noted in some studies, may increase so mysterious title of ‘No occurrences of neural tube the risk of diabetes, cardiovascular disease and the defects among 382 women on dolutegravir at preg- development of some cancers. Tenofovir disproxil nancy conception in Brazil’ [1] , so nothing to report fumarate (TDF) is associated with lower body weight, here but the title, however the main show was from compared to tenofovir alafenamide fumarate (TAF), Rebecca Zash, from Harvard TH Chan School of Public abacavir or NRTI-sparing treatment. The NAMSAL trial Health, Boston, who presented results on neural tube was carried out for 96 weeks on 613 treatment naïve defects by antiviral and HIV exposure in the Tsepamo patients in Cameroon, who were randomised to TDF/ Study, Botswana. Zash discussed the previous 0.94% FTC + DTG or TDF/FTC/EFV. The ADVANCE trial was prevalence of NTD that was reported in 2018, the new conducted over 96 weeks where 1053 treatment-naïve results took in an expanded cohort from 8 to 18 patients in South Africa were randomised to TAF/FTC 74 © Mediscript Ltd 2019

005_HIV_19_3_07.indd5_HIV_19_3_07.indd 7474 88/29/2019/29/2019 5:28:585:28:58 PMPM Conference Report HIV Nursing 2019; 19(3): 74–77 + DTG, TDF/FTC + DTG or TDF/FTC/EFV. Weight gain Injectable cabotegravir and rilpivirine, a combination was more evident in DTG and TAF-based treatment, in of two long-acting, anti-HIV drugs taken once monthly, both studies women gained more weight than men [5] . has been shown to have a very low rate of treatment Moorhouse recommended further study and looking at failure and a favourable safety profi le [10] , and the the effects in different populations. Watch this space. phase III ATLAS (Antiretroviral therapy as long-acting suppression) trial evaluated injectable cabotegravir plus rilpivirine in people who switched from a standard Vaccine and cure oral combination regimen with fully-suppressed viral There were new results from two separate vaccine load [11] , while the FLAIR (First long-acting injectable trials. The fi rst, was from a phase II vaccine study, regimen) trial tested the injectable combination in APPROACH, which indicated that the antibody and people starting HIV treatment for the fi rst time [12] . cellular immune responses induced by the vaccine In ATLAS, one-third of the 616 treatment-experienced lasts for at last 2 years, and that a protective antibody participants were women, two-thirds were white, about response could last for at least 5 years if it declined one-quarter were black and the median age was 42 at a rate typical of other vaccines [8] . Furthermore, years. They had been on ART for a median of 4 years, even after 5 years, the level of anti-HIV antibodies in all had viral suppression and the median CD4 count the blood of vaccine recipients was greater than the was 653 cells/mm3 . After 44 weeks on the injectable level seen that protected two-thirds of monkeys in regimen, 97% of participants who switched said they pre-clinical challenge experiments. The results pre- preferred the long-acting treatment and although there sented at IAS showed that the antibody response was some injection site irritation and pain only one produced by the APPROACH vaccine peaked after person stopped due to this. The FLAIR trial showed a the last inoculation in the four-injection regimen and similar response with Murray et al. presenting ‘Patient declined about tenfold in the fi rst 5 months afterwards. reported outcomes on long-acting cabotegravir + rilpi- Subsequently, however, it had scarcely declined any virine as maintenance therapy: FLAIR 48 week results ’ further during the following 2 years. About one-quarter stating that the results ‘are reassuring and indicate of vaccine recipients showed no immune response to that long-acting injectable treatment meets partici- the fi rst injection, however, all initial non-responders pants’ expectations despite its potential challenges in fact did respond to the second vector dose, as well (e.g. injection-site reactions or visits to a healthcare as to the third and fourth doses [8] . APPROACH professional) ’, concluding that the fi ndings ‘support participants who received the two most effi cacious the therapeutic value and acceptability of monthly regimens will continue to be followed-up for the next injectable long-acting therapy, providing an additional 3 years to see how their immune response changes treatment choice for people living with HIV .’ [12] over time. The second presentation on vaccine trials Pifeltro and Delstrigo – MSD’ s new drug doravirine was also from a second phase II vaccine study, ASCENT had its global seal of approval in various discussions. [9] . The results from this study have settled the question Islatravir (ISL), a long-lasting nucleoside reverse tran- of which vaccine formulation to use in the forthcoming scriptase translocator inhibitor (NRTTI) was formally phase III effi cacy study called MOSIACO which will known in studies as MK-8591 [13] . This novel drug launch this autumn with 3800 gay and bisexual men has been shown in initial trials to be highly effective and transgender women taking part in North America, and long lasting leading to discussions of implants South America and Europe. Results from all trials will and reduced dosing to weekly or monthly. In his talk be out in 2022/2023. around two-drug regimens Argentina’ s Pedro Cahn queried the end of efavirez: ‘so long old friend you’ ve ART, Two-drug regimens, injectables served us well ’. and implants A silicone vaginal ring containing the antiretroviral drug dapivirine continued to demonstrate moderate effec- Dolutegravir received a further boost (after the neural tiveness and remained well tolerated and acceptable tube defect issue) as the WHO updated its 2019 to African women over a year-long period [14–16] . In guidelines, to recommend dolutegravir in combination an open-label extension of the randomised ASPIRE with two nucleoside reverse transcriptase inhibitors trial, nearly three-quarters of the participants opted (NRTIs) for fi rst-line treatment of all adults and ado- to use the ring for the full 2-year follow-up period, lescents with efavirenz 400mg plus two NRTIs as an and researchers estimated that it reduced the risk of alternative fi rst-line regimen for adults and adolescents. acquiring HIV by 39%. In previous trials results have Whereas WHO previously recommended efavirenz ranged from 27% to 90% but these varied depending 600mg, it now supports the lower dose of 400mg that upon usage and adherence. Final results from this has benefi ts in terms of side effects and cost. open-label extension trial of the dapivirine vaginal ring Dolutegravir and lamivudine (Dovato) had new 96-week indicated high uptake and adherence, a well-tolerated GEMINI trial data launched at IAS that showed contin- safety profi le consistent with that seen in the phase ued effi cacy and non-inferiority to other ART. However, III studies and lower HIV-1 incidence than expected again with dolutegravir and TAF-based treatments the [14] . At the press conference Baeten stated: weight-gain red fl ag was raised, mainly in females who ‘ Having both PrEP and the dapivirine ring would be a are black via the ADVANCE trial [5] . signifi cant milestone for HIV prevention, because the 75

005_HIV_19_3_07.indd5_HIV_19_3_07.indd 7575 88/29/2019/29/2019 5:28:585:28:58 PMPM HIV Nursing 2019; 19(3): 74–77 Conference Report more options the better … no one method is going PrEP as while they were on it, and concerningly, it to be right for all women, and no method will be, nor was highlighted that this type of person’ s ‘perceived can be effective, if it’ s not used or not available in the risk may be lower than their actual risk’. However, a fi rst place. ’ survey of young gay and bisexual men and transgender women in Chicago, where a proportion of them were Drug dosing taking PrEP, has found no direct relationship between There was quite a controversial study, ‘QUATUOR’ starting PrEP and any increase in STIs. Although it did [17] , which looked a dosing ART for 4 consecutive fi nd that people started having more condom-less anal days a week with 3 days off. The study did not use a sex after starting PrEP this did not translate into more single regimen, instead it randomised 647 people with STIs [22] . There was also news of a potential once-a-year fully suppressed viral loads taking a variety of ART to injectable in the form of an islatravir implant, which continue taking their medication 7 days a week or to has undergone a small study to look at safety and change to taking medication on 4 consecutive days. tolerability, there were reported issues of site irritation, Not only did the study fi nd no difference between bleeding and itching but these were seen as tolerable these strategies, but no signifi cant difference in the by the 16 initial participants. virological safety of the two strategies. Previous studies The role of stigma in PrEP was discussed with an in 100 people found that 96% of people were able interesting study from Kenya, presented by Daniel Were to maintain an undetectable viral load throughout [23] , which identifi ed three different types of stigma: the follow-up period after changing to 4-day-a-week treatment [18,19] . Although this 2019 study stated ■ Product stigma: ‘I have kept it a secret because the success there were cases of failure and this was high- bottle is similar to that of ARVs. Someone who lighted with virological failure occurring in 1.9% of the doesn’ t know about PrEP could think you have HIV.’ 4-day group and 1.3% of the continuous-treatment (Woman, aged 20 years) group. There was no signifi cant difference in the ■ Identity stigma: ‘MSM is seen as something bad, rate of failure according to the third agent (integrase they take it as a curse …’ (MSM, aged 20 years. inhibitor, NNRTI or PI) used. Although the number This form of stigma was mainly cited by MSM and of participants developing drug resistance was small sex workers) (four out of ten cases of virological failure) three out ■ Behaviour stigma: ‘My mother told me I have taken of four developed two-class resistance to drugs in the those drugs because I want to be a prostitute …’ NRTI backbone and to either rilpivirine (two cases) or (Woman, aged 22 years. This was mainly cited by raltegravir (one case).There was no difference in the rate adolescent girls and young women) of adverse events between the study arms, but kidney Similar threads came from another study in South function showed a small trend towards improvement Africa [24] . Both presenters emphasised prioritising in the 4-day arm at week 48. Landman said that the tailored interventions that include sensitivity training for 4-day strategy reduced the cost of treatment by 43%. healthcare providers and raising awareness of PrEP in During audience questions the authors stated they were efforts to normalise and destigmatise it. The future of looking at further pharmacokinetic data for reasons PrEP moves on … just stigma and the funding hurdles why some people developed virological issues and on to jump. which drugs, and also monitoring how many drugs were taken in each arm as this appeared to be somewhat hazy; therefore the 4-day participants may have taken 90-90-90 more, the 7-day participants may have taken less. It The UNAIDS 90-90-90 targets were mentioned was further raised that until more data came out, this throughout as was the need and challenge of solving may be a risky strategy to promote unless we know the 10-10-10 targets and the successes and inequalities what drugs regimens are safe to reduce in this manner. around the world with access to medication and services. There were launches for fast-track city initia- PrEP developments tives with London taking on a global conference. Pre-exposure prophylaxis (PrEP) fi nally got the global go-ahead with many discussions around PrEP promo- Conclusion tions with monitoring and changes to guidance on Sometimes IAS conferences yield very little new data event-driven PrEP (taken before and after sex also but 2019 is a bumper year of new innovations and called on demand or 2+ 1 + 1) added to the WHO’ s exciting times ahead, but this also highlighted inequali- updated recommendations. The effects of PrEP and ties in studies particularly the lack of women in trials usage was highlighted in studies from Australia [20] (raised in questions several times) and the increasing and Brazil [21] , with the most consistent fi nding that effect of stigma, which was a thread throughout the young people have diffi culty maintaining PrEP use: conference. The future is exciting with new ART, in the studies, youth was the single most signifi cant reduced dosing and new ways of delivery. I’ ll leave predictor of PrEP discontinuation, although the drop-out the last word to Professor Chloe Orkin who said: rate was lower in the Brazilian study. The Australian ‘The future is here … but it ’ s our collective responsibility study showed that people ’s risk of sexually transmitted to deliver innovation everywhere, to everyone including infections (STIs) was just as great after they stopped women and children. ’ 76

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