ViralEd - AIDS e-Newsletter 2022

Doxycycline post-exposure prophylaxis for STI prevention among MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI's in a randomized trial (Luetkemeyer A, et al; Abstract OALBX0103):
Luetkemeyer et al reported the results of the DoxyPEP study of the use of 200 mg of doxycycline as post-exposure prophylaxis (PEP) within 72 hours of unprotected sex in 554 MSM and TGW who were either HIV infected or at risk on PrEP in Seattle and San Francisco. The overall incidence of all STIs was 10.3% among doxy recipients and 29% in the placebo group, with similar findings for people with HIV and PrEP users. Differences were greatest for gonorrhea, followed by chlamydia and syphilis. These data are comparable to the findings of the IPERGAY study of doxycycline pre-exposure prophylaxis among MSM. 16% of subjects took ≥20 doses/month, and 30% took 10-20 doses/month. Adverse events were limited and as expected. The authors cautioned that other key data are not yet available, such as the impact of this intervention on drug resistance in the community, the effect on individual and community microbiomes, and the potential for disinhibition and altered sexual behavior. Nonetheless, the 65% reduction in all STIs with DoxyPEP in this self-selected population of individuals with a specific known increased risk of STIs is an important advance in STI prevention and management.

Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE) (Avihingsanon A, et al; Abstract OALBX0105):
Avihingsanon et al reported on the 48-week results of the ALLIANCE trial in which BIC/FTC/TAF was compared to DTG + TDF/FTC in 243 individuals with HIV and HBV coinfection. The study was designed as a non-inferiority trial with a margin of 12%, and the primary endpoints were an undetectable HIV viral load <50 copies/mL and an undetectable HBV DNA <29 IU/mL at week 48. In the HIV analysis, BIC/FTC/TAF was non-inferior to DTG + TDF/FTC, with 95% and 91% respectively achieving a VL <50 mg/dL. In the hepatitis B comparison, BIC/FTC/TAF was superior, with 63% achieving an undetectable HBV viral load, compared to 43% in the DTG + TDF/FTC arm. More patients in the BIC/FTC/TAF arm achieved ALT normalization, HBeAg seroconversion, and HBsAg loss. The safety profile of both regimens was as expected and not significantly different between the arms. These data provide an interesting additional perspective on the relative activity of the second generation INSTIs in people with HIV and HBV coinfection.

Trends in PrEP inequity by race and census region, United States, 2012-2021 (ALLIANCE)
(Sullivan P, et al; Abstract OALBX0106):
Sullivan et al presented an equity analysis of PrEP use in the U.S. using available pharmacy fill data. Only 34% of data sources provided race and ethnicity data, and this analysis extrapolated from these 124,835 individuals, which was noted to be a major limitation of the study. Nonetheless, the PrEP-to-Need ratio, i.e., the number of PrEP prescriptions filled divided by the number of incident HIV infections in a region, showed substantial inequities in PrEP prescriptions relative to the need. For example, in the Midwest, the ratio was 28.3 for Whites, 7.5 for Latino/as, and 3.0 for Blacks, and this trend was similar in all regions of the U.S., with the greatest disparity in the Northeast. These data will be available to clinicians and researchers by region on AIDSVu. This study offers a major advance in the development of equity metrics that measure our progress, or lack of progress, towards equity in access to effective HIV prevention tools in the U.S.

The effect of the COVID-19 pandemic on access to HIV Treatment and vertical transmission: results from the Canadian Perinatal HIV Surveillance Program
(Sauve L, et al; Abstract OAC0204):
Sauve et al investigated the impact of COVID-19 on pregnant women with HIV in Canada using data from the Canadian Perinatal HIV Surveillance Program. Of the 250 women evaluated in 2020, 21% were indigenous, 13% were White, and 60% were Black. The perinatal transmission rate was 3.2% during the pandemic, compared to 1.4% from 2015-2019, and highest among IDUs (26.1%) compared to 13.6% among IDUs in the earlier period. These data underscore the powerful disruption of services during the COVID-19 years, as well as the disproportionate impact on people of color and indigenous peoples in Canada.

Indigenous responses to HIV; the opioid epidemic (Bruneau J, et al; Prime Session):
Julie Bruneau, the Canada Research Chair of Addiction Medicine, gave a powerful overview of the global opioid crisis. She noted that 30,000 Canadians have died from opioid OD in the past 8 years, and that daily deaths from opioid OD exceeded 100 in the United States last year. She reported substantial increases in opioid use in Africa and Eastern and Southern Asia in the past decade. Dr. Bruneau included another dimension of the crisis, i.e., the inability of clinicians to effectively treat pain in resource-limited settings where opioid supplies are low or nonexistent, and in the global north, where restrictive policies are limiting patient access to critical pain treatment. She concluded with an impassioned plea for international governmental funding to support the universal benefits of harm reduction and opioid substitution therapy as proven by evidence-based strategies that have been shown to reduce HIV and HCV incidence, as well as overall mortality and deaths from overdose, among PWIDs.

Dual therapy based on DRVr plus 3TC in HIV-1 naïve patients: global 48-week results from ANDES Study (Figueroa M, et al; Abstract OAB0303):
Figueroa et al presented the 48-week results of the ANDES study that compared dual therapy with DRV/r + 3TC to DRV/r + 3TC/TDF in 336 HIV-1 naïve patients with a median CD4 cell count of 415 copies/mL and viral load of 4.5 log10. 23% of patients had a VL >100,000, and 7%-9% had a CD4 cell count <200 copies/mL. In the ITT analysis, 91% and 93% of subjects had VL <50 copies/mL at 48 weeks, with no significant difference among patients with a high baseline viral load. No drug resistance was seen among the few virologic failures, and the safety profile was comparable. These findings lend further support to dual therapy with DRV/r + 3TC.

Dolutegravir versus efavirenz-400 as first-line ART in Cameroon: week 192 data of NAMSAL trial (Mpoudi-Etame M, et al; Abstract OAB0304):
Mpoudi-Etame et al presented the final 192-week outcomes of the NAMSAL trial that compared dolutegravir to efavirenz-400 as first-line ART in Cameroon. Among participants, the mean CD4 cell count was 281, one third had CD4 <200 copies/mL, the mean VL was 5.3, and two thirds of subjects had VL>100,000 copies/mL. As was seen at 48 and 96 weeks, DTG was non-inferior to low dose EFV, with 69% of DTG recipients and 62% of EFV recipients achieving a VL <50 copies/mL. Among patients with a VL > 100,000, DTG was superior, with 66% <50 copies/mL compared to 54% of EFV recipients. There were no new safety concerns overall and among 39 pregnant women in the trial. Weight gain was substantial among this cohort with a high proportion of advanced disease, with an average increase of 7 kg with DTG and 5 kg with EFV after 192 weeks. Among women, weight gain above 15% of body weight was seen in 43% of DTG recipients and 31% of EFV recipients. These data further support the efficacy of DTG and EFV in this population and favor the use of DTG in patients with advanced disease.

Are people living with HIV at higher risk of severe and fatal COVID-19?
(Bertagnolio s, et al; Abstract OAB0404):
Bertagnolio et al presented the WHO analysis of 338,566 people who were hospitalized with COVID-19 in 38 countries to compare the mortality in 16,955 PLWHIV to uninfected individuals from Jan 2020 to June 2021. Compared to the global rate of vaccination of 62%, only 18% of people in Africa were vaccinated. Of PWHIV, the mean age was 45 years, 63% were women, 95% of patients were from Africa, and in-hospital mortality overall was 24.7%, which was 51% higher than uninfected individuals. Headache, fever, fatigue, shortness of breath, chest pain, anosmia and myalgia were more frequent in PWHIV, and cough was less frequent. Associated co-morbidities were more common in PWHIV (59%) than in the general population (45%), and 52% of PWHIV had one or two comorbid conditions, with three or more in 7.1% of PWHIV. In-hospital mortality was 1.51x higher among PWHIV, and highest in PWHIV with CD4 <200 cells/mL and VL >1,000 copies/mL. In PWHIV with CD4 >200 and VL <1,000 copies/mL, the relative risk as 1.12x higher. The strongest predictor of mortality was age >60 years (6x higher). Chronic kidney disease and diabetes also independently predicted mortality among PWHIV. Mortality was lower with Omicron than for Delta, Alpha, and Beta, but to a lesser degree among PWHIV. For PLWHIV, mortality in 2022 due to Omicron was 19.8%, compared to 24% in 2020 and 2021, compared to 8.6% among uninfected people during Omicron and 21-22% in earlier periods. These data largely compare COVID mortality in unvaccinated PWHIV with a higher burden of co-morbidities to uninfected individuals of whom the majority were vaccinated. Importantly, PWHIV with higher CD4 cells and VL suppression had an in-hospital mortality that was lower and closer to the general population. The authors concluded with an appeal to increase access to vaccines and treatments in Africa.

National and regional rates of hospitalizations and in-hospital mortality for opportunistic infections for people with HIV in the United States, 2012-2018
(Bielick C, et al; Abstract PESAC10):
Bielick et al presented the national rates of hospitalizations and in-hospital mortality among PWHIV in the U.S. from 2012-2018 based on the Agency for Healthcare Research and Quality's National Inpatient Sample of 145,710 hospitalizations. Two thirds of PWHIV who were hospitalized were male with a median age of 45-55 years, and one half were Black. The rate of OI hospitalization declined from 2,664 to 1,784 per 100,000 from 2012 to 2018. OI hospitalizations resulted in in-hospital mortality in 6.4% of cases in 2012 and 6.0% in 2018. The most common OI hospitalization was for PJP, followed by candida esophagitis, and both remained above 500 per 100,000 in 2018. Surprisingly, PJP remained the most common cause of in-hospital mortality from 2012-2018 and still resulted in 50 deaths per 100,000 individuals, with rates below 25/100,000 for CMV, cryptococcal meningitis, and MAC. The lowest rates were seen for pulmonary tuberculosis and CNS toxoplasmosis. There were substantial regional variations in these data, with the highest rates of hospitalizations and mortality due to OIs in the South, with 2,125 hospitalizations per 100,000 in 2018. These data are a sobering reminder of the ongoing morbidity and mortality due to HIV in the United States, and the wide inequities in access to effective care and treatment by race and by region.

Final week 192 results from the ADVANCE trial: first-line TAF/FTC/DTG, TDF/FTC/DTG vs TDF/FTC/EFV (Hill A, et al; Abstract PELBB01):
Hill et al presented the final 192-week outcomes of the ADVANCE study that compared DTG + TAF/FTC, DTG + TDF/FTC, and EFV/TDF/FTC in 1,053 PWHIV in South Africa. In the ITT analysis, undetectable VL was sustained in 62% with DTG + TAF/FTC, 58% with DTG + TDF/FTC, and 50% with EFV/TDF/FTC, and in the on-treatment analysis, 96%, 98%, and 99%, respectively, were virologically suppressed. Weight gain was 8.9 kg, 5.8 kg, and 3.3 kg, respectively, and the frequency of clinical obesity in each group was 29%, 21%, and 15%, respectively. These adverse events were most common among women, in whom clinical obesity occurred in 43% on DTG + TAF/FTC, 27% on DTG + TDF/FTC, and 20% on EFV/TDF/FTC. These data confirm the virologic superiority of dolutegravir over efavirenz in this population, and call attention to the high rate of weight gain with dolutegravir in this study population that was most frequent and severe in women.

Association of prenatal PrEP exposure with neurodevelopmental and growth outcomes beyond 24 months among Kenyan children (Gomez L, et al; Abstract OAC0502):
Gomez et al (OAC0502) reported on the long-term effects of PrEP on developmental growth and neurodevelopment in children born to 472 mother-child pairs in Kenya. The median age of the women was 28 years. 16% of the women had exposure to PrEP for an average of 3 months. Trained study nurses completed the assessments at 24-30 months using the Ages and Stages Questionnaire. Prenatal PrEP exposure was not associated with any adverse growth outcomes or neurodevelopmental outcomes. These data are reassuring and vitally important in the growing effort to expand PrEP usage in at-risk women worldwide.

High HIV incidence and mortality in a multi-site cohort of transgender women in the eastern and southern United States (Wirtz A, et al; Abstract OAC0403):
Wirtz et al reported on the high HIV incidence rate of 5.5/1,000 patient-years among transgender women over the past 4 years in 78 cities in the eastern and southern U.S. Rates were higher for younger TGW aged 18-24 (8.5/1,000 patient-years) than age >25 years (4.2), for Blacks (19.3) and Latina (9.9) compared to Whites (1.6), for TGW in the South (10.3) than in the North (3.0) or mid-Atlantic states (4.8) and for TGW in whom PrEP was indicated at baseline (11.2). Meaningful reductions in HIV incidence depend on several critical actions to support TGW, including the recognition of the additive vulnerabilities of TGW who are young, Black, and Latina.

Monkeypox: Outbreak and response in non-endemic countries
(Doherty M, Girometti N, Bergeron G, et al; Abstract SY43):

Epidemiology of the current monkeypox outbreak (Doherty M, et al)
Meg Doherty of WHO presented the global status of the monkeypox outbreak. As of July 31, 2022, there were 21,256 cases in 78 countries, with the highest incidence in Europe and the Americas. There were 5 deaths prior to the conference, all in Africa, and during the conference, another 5 deaths were reported from Spain (2), India, Brazil, and Ghana. 98.8% of cases were in men, and 98.1% of cases were in MSM. Of 2,680 cases with known transmission histories, 94.1% of cases were related to close contact including sexual contact, and 160 (12%) were not sexual. The most common exposure settings were parties, bars, and large gatherings. Among the novel clinical syndromes that were different from the earlier epidemics in the Congo and Nigeria were severe proctitis, urinary retention, and urethritis. Hospitalizations occurred in less than 10% of individuals, mostly for pain control, proctitis, secondary infections, and encephalitis. Of 6,098 people with known HIV status, 38% were HIV positive. On July 23, WHO declared that monkeypox was a global health emergency. Dr. Doherty noted that although 16.4 million units of vaccine are available, the bottleneck is the need to accelerate the transformation into useable vials, as well as further global production. Priorities identified from community consultations included the urgent need for accurate information, broad access to vaccines and treatment, health worker training, guidance and support for community members and affected individuals, community contributions that are planned and funded, and measures to counter stigma and discrimination.

The clinical syndrome and treatment (Girometti N, et al)
Nicole Girometti described the first 620 cases of monkeypox at the Chelsea Westminster Hospital, of whom 99% were MSM, 31% were HIV positive, 70% were white, and 62% were born outside of the UK. The mean age was 39 years. Common presenting symptoms were fever (66%), fatigue (4%), myalgia (36%), headache (32%), and sore throat (14%); 17% had no symptoms. Two thirds of patients with prodromal symptoms had a rash at the same time. 99% of patients presented with a characteristic rash, and 93% had ano-genital lesions. Other common sites were limbs (49%), trunk (30%), face (25%), and hands and feet (20%). 6% had oral mucosal involvement. Simultaneous evolution of skin lesions was common, and one third had skin lesions on more than three sites. One third had skin lesions on a single site. Proctitis occurred in 17%, often with severe pain and constipation, and 25% required antibiotic treatment. 35% had a concomitant STI: GC (22%), chlamydia (14%), and syphilis (6%). Practical suggestions for therapy included analgesia, hydration, laxatives, mesalazine enemas for proctitis, surgical I&D for abscesses, and urinary catheterization for retention. In severe cases, opioids were needed for rectal pain.

Public health management and vaccines (Bergeron G, et al)
Bergeron et al reported the experience of the Montreal Health Department with monkeypox from the first reported case in May, 2022. Within one week of the recognition of the first case, vaccination with Jynneos (MVA-BN) vaccine began on May 30, 2022 for post-exposure prophylaxis of known exposures. By June 3, 2022, recognizing the inadequacy of this approach, a modified "PEP+" approach was adopted to include all individuals with potential exposures over the past 14 days, and then on June 14, 2022, a pre-exposure prophylaxis strategy was adopted for cis or trans-gender men who were planning to have sex with cis or trans-gender men outside of a stable monogamous relationship, i.e. with multiple partners. As of August 1, 2022, a total of 15,303 total doses were administered. Monkeypox cases were seen to level off in the week before the conference, though it was too early for this to be conclusive. The investigators reported 39 cases of vaccine failures, and they emphasized the need for both behavior change and vaccination in order to control the outbreak. In an exemplary model of good public health practice, free vaccine was offered to at-risk IAS Conference attendees. This presentation received a standing ovation.


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