Latest DHHS #Guidelines For Initial #HIV Therapy Now Include 5 Choices — But Really 2 Are Best
https://blogs.jwatch.org/hiv-id-observations/index.php/latest-dhhs-guidelines-initial-hiv-therapy-now-include-5-choices-really-2-best/2018/04/08/
Based on this change, there are now five recommended initial regimens for most people:
Bictegravir/TAF/FTC
Dolutegravir/ABC/3TC
Dolutegravir + TAF (or TDF)/FTC
Elvitegravir/cobicistat/TAF (or TDF)/FTC
Raltegravir + TAF (or TDF)/FTC
All are based on an integrase inhibitor and a pair of NRTIs. Four have tenofovir/FTC as the NRTI pair. Three are available as a single tablet, once daily.
But with the important caveat that what follows represents my opinion and not that of these or any other guidelines, one could easily argue that there are really two primary choices here, not five.
And those are dolutegravir + TAF (not TDF)/FTC and, now, bictegravir/TAF/FTC...
https://blogs.jwatch.org/hiv-id-observations/index.php/latest-dhhs-guidelines-initial-hiv-therapy-now-include-5-choices-really-2-best/2018/04/08/
Based on this change, there are now five recommended initial regimens for most people:
Bictegravir/TAF/FTC
Dolutegravir/ABC/3TC
Dolutegravir + TAF (or TDF)/FTC
Elvitegravir/cobicistat/TAF (or TDF)/FTC
Raltegravir + TAF (or TDF)/FTC
All are based on an integrase inhibitor and a pair of NRTIs. Four have tenofovir/FTC as the NRTI pair. Three are available as a single tablet, once daily.
But with the important caveat that what follows represents my opinion and not that of these or any other guidelines, one could easily argue that there are really two primary choices here, not five.
And those are dolutegravir + TAF (not TDF)/FTC and, now, bictegravir/TAF/FTC...
!!
Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining #Cancer Incidence in #HIV-Infected Veterans: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684480/association-viral-suppression-lower-aids-defining-non-aids-defining-cancer
Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 95% CI, 2.19 to 2.51), lower among persons with early suppression (RR, 1.99 CI, 1.87 to 2.12), and lowest among persons with long-term suppression (RR, 1.52 CI, 1.44 to 1.61). This trend was strongest for ADC (unsuppressed: RR, 22.73 CI, 19.01 to 27.19; early suppression: RR, 9.48 CI, 7.78 to 11.55; long-term suppression: RR, 2.22 CI, 1.69 to 2.93), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 CI, 3.24 to 4.49; early suppression: RR, 3.42 CI, 2.95 to 3.97; long-term suppression: RR, 3.17 CI, 2.78 to 3.62), and absent for NADC not caused by viruses
Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.
Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining #Cancer Incidence in #HIV-Infected Veterans: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684480/association-viral-suppression-lower-aids-defining-non-aids-defining-cancer
Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 95% CI, 2.19 to 2.51), lower among persons with early suppression (RR, 1.99 CI, 1.87 to 2.12), and lowest among persons with long-term suppression (RR, 1.52 CI, 1.44 to 1.61). This trend was strongest for ADC (unsuppressed: RR, 22.73 CI, 19.01 to 27.19; early suppression: RR, 9.48 CI, 7.78 to 11.55; long-term suppression: RR, 2.22 CI, 1.69 to 2.93), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 CI, 3.24 to 4.49; early suppression: RR, 3.42 CI, 2.95 to 3.97; long-term suppression: RR, 3.17 CI, 2.78 to 3.62), and absent for NADC not caused by viruses
Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.
!!
#Antiretroviral Drugs for Treatment and Prevention of #HIV Infection in Adults
2018 Recommendations of the International Antiviral Society–USA Panel
https://jamanetwork.com/journals/jama/fullarticle/2688574#193815836
ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV.
Conclusions and Relevance Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.
#Antiretroviral Drugs for Treatment and Prevention of #HIV Infection in Adults
2018 Recommendations of the International Antiviral Society–USA Panel
https://jamanetwork.com/journals/jama/fullarticle/2688574#193815836
ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV.
Conclusions and Relevance Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.
!!
#Neurocognitive development in perinatally #HIV-infected adolescents on long-term treatment compared to healthy matched controls: a longitudinal study
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz386/5492020
Cross-sectional analysis of the NOVICE cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated perinatally HIV-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV-).
Processing speed, working memory, learning ability and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at older age deviated more in executive functioning (-0.13 z-score, 95%CI -0.24 to -0.02, p=0.043). The prevalence of cognitive impairment by MNC was similar in both groups at both time-points.
Conclusions
cART-treated PHIV+ adolescents appear to have similar global cognitive development compared to healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.
#Neurocognitive development in perinatally #HIV-infected adolescents on long-term treatment compared to healthy matched controls: a longitudinal study
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz386/5492020
Cross-sectional analysis of the NOVICE cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated perinatally HIV-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV-).
Processing speed, working memory, learning ability and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at older age deviated more in executive functioning (-0.13 z-score, 95%CI -0.24 to -0.02, p=0.043). The prevalence of cognitive impairment by MNC was similar in both groups at both time-points.
Conclusions
cART-treated PHIV+ adolescents appear to have similar global cognitive development compared to healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.
OUP Academic
Neurocognitive development in perinatally HIV-infected adolescents on long-term treatment compared to healthy matched controls:…
AbstractBackground. Cross-sectional analysis of the NOVICE cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated
!!
Preexposure #Prophylaxis for the Prevention of #HIV Infection
https://jamanetwork.com/journals/jama/fullarticle/2735509
The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine..
The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate–based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial.
Conclusions and Recommendation The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation)
Preexposure #Prophylaxis for the Prevention of #HIV Infection
https://jamanetwork.com/journals/jama/fullarticle/2735509
The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine..
The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate–based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial.
Conclusions and Recommendation The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation)
Jamanetwork
USPSTF Guideline: Preexposure Prophylaxis for the Prevention of HIV Infection
This 2019 Recommendation Statement from the US Preventive Services Task Force recommends offering preexposure prophylaxis (PrEP) with effective antiretroviral therapy to persons at high risk of HIV acquisition (A recommendation).
!!
Sequential #LASER ART and CRISPR Treatments Eliminate #HIV-1 in a Subset of Infected Humanized Mice
https://www.nature.com/articles/s41467-019-10366-y
Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice.
HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected.
...These data provide proof-of-concept that permanent viral elimination is possible.
Sequential #LASER ART and CRISPR Treatments Eliminate #HIV-1 in a Subset of Infected Humanized Mice
https://www.nature.com/articles/s41467-019-10366-y
Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice.
HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected.
...These data provide proof-of-concept that permanent viral elimination is possible.
Nature
Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Nature Communications - Here, the authors show that sequential treatment with long-acting slow-effective release ART and AAV9- based delivery of CRISPR-Cas9 results in undetectable levels of virus...
Effect of #Zinc Supplementation vs Placebo on Mortality Risk and #HIV Disease Progression Among HIV-Positive Adults With Heavy #Alcohol Use
https://2medical.news/2020/07/03/effect-of-zinc-supplementation-vs-placebo-on-mortality-risk-and-hiv-disease-progression-among-hiv-positive-adults-with-heavy-alcohol-use/
.. A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in …
https://2medical.news/2020/07/03/effect-of-zinc-supplementation-vs-placebo-on-mortality-risk-and-hiv-disease-progression-among-hiv-positive-adults-with-heavy-alcohol-use/
.. A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in …
Risk of failure in dual therapy versus triple therapy in naïve #HIV-patients: a systematic review and meta-analysis
https://2medical.news/2020/10/18/risk-of-failure-in-dual-therapy-versus-triple-therapy-in-naive-hiv-patients-a-systematic-review-and-meta-analysis/
Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities.. ..Fourteen studies were included, allowing a meta-analysis on 5,205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the relative risk (RR) of treatment failure (TF) (RR>1 favoring triple therapy) in 10 studies was 1.20 (95%CI: 0.91-1.59, I 2: 49.2%); the RR of …
https://2medical.news/2020/10/18/risk-of-failure-in-dual-therapy-versus-triple-therapy-in-naive-hiv-patients-a-systematic-review-and-meta-analysis/
Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities.. ..Fourteen studies were included, allowing a meta-analysis on 5,205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the relative risk (RR) of treatment failure (TF) (RR>1 favoring triple therapy) in 10 studies was 1.20 (95%CI: 0.91-1.59, I 2: 49.2%); the RR of …
#COVID-19 Outcomes Among Persons Living With or Without Diagnosed #HIV Infection in New York State
https://2medical.news/2021/02/06/covid-19-outcomes-among-persons-living-with-or-without-diagnosed-hiv-infection-in-new-york-state/
New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level.. ..A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] …
https://2medical.news/2021/02/06/covid-19-outcomes-among-persons-living-with-or-without-diagnosed-hiv-infection-in-new-york-state/
New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level.. ..A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] …