HIV
RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background
28 Nov, 2024 | 12:38h | UTCBackground: Although preexposure prophylaxis (PrEP) effectively reduces HIV transmission, adherence to daily oral regimens is suboptimal among high-risk populations. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, has shown efficacy in cisgender women, but its efficacy in men and gender-diverse individuals remains unclear.
Objective: To evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir compared to background HIV incidence and daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among men and gender-diverse persons.
Methods: In this phase 3, double-blind, randomized trial, 3,271 HIV-negative participants were assigned in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral F/TDF, with matching placebos. Participants were cisgender men, transgender women and men, and gender-nonbinary persons aged 16 or older who have sex with male-assigned partners. The primary endpoint compared HIV incidence in the lenacapavir group to background incidence; secondary analysis compared lenacapavir to F/TDF.
Results: In the modified intention-to-treat analysis (n=3,265), HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). The background HIV incidence was 2.37 per 100 person-years. Lenacapavir significantly reduced HIV incidence compared to background (incidence rate ratio [IRR], 0.04; 95% CI, 0.01–0.18; P<0.001) and F/TDF (IRR, 0.11; 95% CI, 0.02–0.51; P=0.002). No significant safety concerns emerged. Injection-site reactions led to discontinuation in 1.2% of lenacapavir recipients and 0.3% of F/TDF recipients.
Conclusions: Twice-yearly subcutaneous lenacapavir significantly reduced HIV incidence compared to both the background incidence and daily oral F/TDF among men and gender-diverse persons. These findings support lenacapavir as an effective PrEP option in this population.
Implications for Practice: The introduction of a long-acting, twice-yearly injectable PrEP option like lenacapavir could improve adherence and uptake among populations challenged by daily oral regimens.
Study Strengths and Limitations: Strengths include a large, diverse participant population with significant representation of transgender and gender-nonbinary persons, and the use of an active comparator. The novel counterfactual design estimating background HIV incidence avoided ethical issues of placebo controls but may have limitations in accuracy. Limitations include a relatively short follow-up and potential impact of injection-site reactions on adherence. The emergence of resistance mutations in participants who acquired HIV while on lenacapavir is a concern needing further investigation.
Future Research: Further studies should assess the long-term safety, efficacy, and resistance patterns associated with lenacapavir use. Research into optimizing injection techniques to minimize injection-site reactions and exploring lenacapavir’s applicability in other at-risk populations is recommended.
Observational Study: Kidney Transplantation from Donors with HIV Safe for Recipients with HIV
20 Oct, 2024 | 17:30h | UTCBackground: Kidney transplantation improves survival for persons with HIV and end-stage renal disease but is limited by organ shortages. Transplantation from donors with HIV to recipients with HIV is emerging under the HIV Organ Policy Equity (HOPE) Act but is currently approved only for research. The Department of Health and Human Services is considering expanding this practice to clinical care, but data are limited to small case series without control groups.
Objective: To assess whether kidney transplantation from donors with HIV is noninferior to transplantation from donors without HIV regarding safety outcomes in recipients with HIV.
Methods: In an observational, noninferiority study at 26 U.S. centers, 408 transplantation candidates with HIV were enrolled. Of these, 198 received a kidney transplant: 99 from deceased donors with HIV and 99 from deceased donors without HIV. The primary outcome was a composite safety event (death, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (upper bound of 95% CI for hazard ratio ≤3.00). Secondary outcomes included overall survival, survival without graft loss, rejection rates, infections, cancer, and HIV superinfection.
Results: The adjusted hazard ratio for the composite primary outcome was 1.00 (95% CI, 0.73 to 1.38), demonstrating noninferiority. Overall survival at 1 year was 94% for recipients of kidneys from donors with HIV and 95% for those from donors without HIV; at 3 years, survival was 85% and 87%, respectively. Survival without graft loss at 1 year was 93% vs. 90%; at 3 years, 84% vs. 81%. Rejection rates were similar at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer did not differ significantly between groups. HIV breakthrough infection occurred more frequently among recipients of kidneys from donors with HIV (incidence rate ratio 3.14; 95% CI, 1.02 to 9.63), primarily due to nonadherence to antiretroviral therapy; viral suppression was regained in all cases. One potential HIV superinfection occurred without clinical consequences.
Conclusions: Kidney transplantation from donors with HIV to recipients with HIV was noninferior to transplantation from donors without HIV regarding safety outcomes, supporting the expansion of this practice from research to clinical care.
Implications for Practice: Expanding kidney transplantation involving donors and recipients with HIV to clinical practice could increase organ availability and reduce disparities in transplantation access for persons with HIV. Clinicians should monitor for HIV breakthrough infections and encourage adherence to antiretroviral therapy.
Study Strengths and Limitations: Strengths include a multicenter design and direct comparison groups. Limitations involve the observational design, inability to randomize due to allocation constraints, and heterogeneity in immunosuppression protocols.
Future Research: Further studies are needed to confirm these findings, evaluate long-term outcomes, and assess potential risks such as HIV superinfection.
RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med
18 Aug, 2024 | 13:56h | UTCStudy Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.
Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.
Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.
WHO report on HIV drug resistance – Rising dolutegravir resistance and implications for global care standards
27 Apr, 2024 | 16:08h | UTCThe World Health Organization’s latest HIV Drug Resistance Report highlights both the effectiveness and emerging challenges with dolutegravir (DTG)-based therapies. While there is significant suppression of HIV viral loads in populations treated with DTG, data reveals increasing resistance levels, particularly among those with high viral loads and prior treatment experiences. The report calls for enhanced surveillance and management strategies to address these resistance patterns and maintain treatment efficacy. It also underscores the necessity of robust data systems and proactive healthcare policies to improve the overall quality of HIV treatment and prevent the transmission of resistant HIV strains, aligning with global efforts to combat antimicrobial resistance.
Source:
New report documents increase in HIV drug resistance to dolutegravir – World Health Organization
RCT | Bictegravir regimen noninferior to dolutegravir regimen in HIV-1, HBV co-infection treatment
31 Jul, 2023 | 14:00h | UTC
RCT | Pitavastatin effective in the primary prevention of cardiovascular disease in HIV-infected individuals
26 Jul, 2023 | 13:35h | UTCPitavastatin to Prevent Cardiovascular Disease in HIV Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Commentaries:
Pitavastatin lowers risk of cardiovascular events in people living with HIV – Aidsmap
Statins reduce cardiovascular risk in people living with HIV, new global study finds – STAT
Pitavastatin Cuts MACE in HIV-Infected Patients: REPRIEVE – TCTMD
Commentary on Twitter
Original Article: Pitavastatin to Prevent Cardiovascular Disease in HIV Infection https://t.co/HuR0Lt24N5
Editorial: HIV and Cardiovascular Disease — An Ounce of Prevention https://t.co/fsxCqrLKi0#IAS2023 pic.twitter.com/TCSQkJQNYa
— NEJM (@NEJM) July 24, 2023
New WHO guidance on the role of HIV viral suppression in improving individual health and reducing transmission
24 Jul, 2023 | 13:17h | UTCNews Release: New WHO guidance on HIV viral suppression and scientific updates released at IAS 2023 – World Health Organization
WHO Guidance: The role of HIV viral suppression in improving individual health and reducing transmission – Word Health Organization
Related WHO Guidelines:
WHO recommends optimizing HIV testing services – World Health Organization
Primary health care and HIV: convergent actions – World Health Organization
Systematic Review | Low-level HIV viremia (below 1000 copies/mL) linked to minimal sexual transmission risk
24 Jul, 2023 | 13:15h | UTCThe risk of sexual transmission of HIV in individuals with low-level HIV viraemia – The Lancet
Editorial: HIV is sexually untransmittable when viral load is undetectable – The Lancet
Related: Study: Growing Acceptability of “Undetectable = Untransmittable” but Widespread Misunderstanding of HIV Transmission Risk Persists (several texts on the subject)
Commentary on Twitter
People on ART with low but detectible levels of HIV viral load have almost zero risk of sexually transmitting the virus to others, in-depth review suggests #IAS2023https://t.co/wU26C8cEMK pic.twitter.com/hQHLDqPxO6
— The Lancet (@TheLancet) July 22, 2023
Cohort Study | Increased risk of depression and suicide among people with HIV, especially in the first two years post-diagnosis
24 Jul, 2023 | 13:01h | UTC
Commentary on Twitter
Risk of Depression in People With HIV: A nationwide population-based matched cohort study
✅ Just Accepted
? Freely Availablehttps://t.co/nyrzPqRRqw— Clinical Infectious Diseases (@CIDJournal) July 22, 2023
Cohort Study | Long-acting antiretroviral therapy may achieve virologic suppression in HIV patients with adherence challenges
17 Jul, 2023 | 13:26h | UTCDemonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV – Annals of Internal Medicine (link to abstract – $ for full-text)
Commentary: Long-Acting ART Achieves Virologic Suppression for People With HIV – HealthDay
RCT | Dolutegravir is noninferior as a replacement for ritonavir-boosted protease inhibitor in HIV therapy
27 Jun, 2023 | 13:52h | UTCSummary: This randomized clinical trial (RCT) assessed the switch from ritonavir-boosted protease inhibitor (PI) to dolutegravir in HIV patients without genotype information but with viral suppression. The multicenter, open-label trial, involving 795 participants across four sites in Kenya, compared those who switched to dolutegravir (398) with those continuing with their current ritonavir-boosted PI regimen (397). The primary end point was an HIV type 1 RNA level of at least 50 copies per milliliter at week 48.
At the end of the trial period, the number of patients in both groups who met the primary end point was nearly the same (5.0% in the dolutegravir group and 5.1% in the ritonavir-boosted PI group). This indicates the noninferiority of dolutegravir, within a 4% margin. Additionally, no mutations conferring resistance to either drug were detected. The incidence of treatment-related adverse events of grade 3 or 4 was similar in both groups (5.7% for dolutegravir and 6.9% for ritonavir-boosted PI).
The study concludes that dolutegravir is a noninferior alternative to ritonavir-boosted PI for previously treated, virally suppressed HIV patients lacking drug-resistance mutation data. The similar safety profiles also support the switch. However, further research may provide valuable insights on the long-term implications of the switch.
Article: Second-Line Switch to Dolutegravir for Treatment of HIV Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Second-Line Switch to Dolutegravir Noninferior in HIV – HealthDay
Commentary on Twitter
In an open-label, multicenter trial in Kenya, HIV-infected patients following a ritonavir-boosted protease inhibitor regimen were assigned to switch to dolutegravir or continue the regimen. The dolutegravir-based regimen was noninferior. https://t.co/jL70h5ejnV
— NEJM (@NEJM) June 21, 2023
RCT | Evaluating the viability of dolutegravir monotherapy in primary HIV infection
27 Jun, 2023 | 13:50h | UTCSummary: The study in focus is a randomized, controlled, non-inferiority trial spanning over 192 weeks, titled “EARLY-SIMPLIFIED”. It evaluated the effect of simplifying combination antiretroviral therapy (cART) to dolutegravir (DTG) monotherapy in patients with early-stage HIV-1 infection. The trial recruited 101 people who had begun cART within 180 days of a documented primary HIV-1 infection with suppressed viral load.
The patients were randomly divided into two groups: DTG monotherapy (n=68) and continued cART (n=33). The primary endpoints were viral failure rates at 48, 96, 144, and 192 weeks. Results revealed no difference in viral response between the two groups at 96 weeks, suggesting non-inferiority of DTG monotherapy. At the end of the trial (192 weeks), no virological failures were recorded in either group.
The study indicates that early initiation of cART during primary HIV infection might permit sustained virological suppression after switching to DTG monotherapy. However, the study was limited by its highly selected patient population and the transition to an observational design after 96 weeks. It provides insight into the potential for minimizing ART toxicity by stratifying patients according to the latent reservoir size or duration of active infection before starting therapy.
Review | Update on the management of patients with HIV infection in anesthesia and critical care
26 Jun, 2023 | 00:36h | UTC
M-A | CRP at 5 mg/L cut-off efficient for tuberculosis screening in HIV outpatients
21 Jun, 2023 | 13:30h | UTC
Commentary on Twitter
ERR: C-reactive protein at a 5 mg cut-off and two newly developed clinical prediction models from this study show clinical utility for TB screening among outpatient PLHIV, while the WHO-recommended four-symptom screen showed suboptimal clinical utility https://t.co/msm13KXR0Y pic.twitter.com/O0wS1Xv4da
— ERS publications (@ERSpublications) June 11, 2023
Cryptococcosis: 90% cases in HIV-negative patients, Australasian study identifies risk factors
5 Jun, 2023 | 12:52h | UTC
Cohort Study | Association of HIV infection and incident abdominal aortic aneurysm
31 May, 2023 | 13:55h | UTC
Phase 2 RCT | Single high-dose L-AmB shows comparable efficacy to standard treatment in HIV/AIDS-related histoplasmosis
29 May, 2023 | 10:41h | UTCSee also: Visual Abstract
A humorous peek into HIV research papers: a quick guide
18 May, 2023 | 13:46h | UTCTypes of HIV Papers — A Quick Guide – HIV and Observations
Commentary on Twitter
In his latest HIV and ID Observations post, @PaulSaxMD presents a quick guide to the different types of HIV papers, comic style. https://t.co/RYW6MuubCd (H/T @xkcd) pic.twitter.com/Zlh7PJOh8o
— NEJM Journal Watch (@JWatch) May 16, 2023
RCT | ART intensification shows no benefit in treating HIV-associated neurocognitive impairment
18 May, 2023 | 13:31h | UTC
Cohort Study | Infection-unrelated cancers are increasingly more common than infection-related cancers among individuals with HIV
2 May, 2023 | 13:32h | UTCAge and Cancer Incidence in 5.2 Million People With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study – Clinical Infectious Diseases (free for a limited period)
Commentary: Infection-Unrelated Cancers Predominant Among Older Adults With HIV – Cancer Therapy Advisor
Commentary on Twitter
Age and Cancer Incidence in 5.2 Million People With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study
? Freely Availablehttps://t.co/LMlF30Zkry
— Clinical Infectious Diseases (@CIDJournal) April 30, 2023
Podcast | HIV in primary care
6 Apr, 2023 | 13:13h | UTC#388 HIV in Primary Care with Dr. Jonathan J. “JJ” Nunez MD – The Curbsiders
Cohort Study | Barriers to starting direct-acting antiviral treatment despite access for HIV & hepatitis C patients
6 Apr, 2023 | 13:09h | UTCInvited Commentary: The road to hepatitis C virus elimination – The Lancet Public Health
Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment?
30 Mar, 2023 | 13:49h | UTC
M-A | Factors associated with post-treatment control of viral load in HIV-infected patients
29 Mar, 2023 | 12:56h | UTC
Updated recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission
15 Mar, 2023 | 15:22h | UTC