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Highlights from the 21st CROI
Newsdesk
Highlights from the 21st CROI Scientists and clinicians gathered in Boston for the annual Conference on Retroviruses and Opportunistic Infections (CROI). Rebecca Cooney and Peter Hayward report. No virus, no risk?
detectable virus in the days after birth, but was subsequently virologically suppressed. She was lost to care, but despite treatment cessation viral load did not rebound. Deborah Persaud and colleagues reported that at age 39 months, 21 months after stopping ART, the child has undetectable viral load; despite low-level persistence of proviral DNA in circulating peripheral blood mononuclear cells, no replicationcompetent DNA was detected. Persaud also reported another child born to a mother with very high viral load and started on nevirapine by 4 h of age. HIV infection was confirmed by peripheral blood HIV DNA at 4 h of life, HIV RNA at 36 h, and CSF virus detection at 6 days. However, at 9 months the child has undetectable virus or viral DNA (abstr 75LB). The IMPAACT trial network now aims to recruit prospectively 54 infants being born to mothers with high viral loads who will start very early treatment, with a planned treatment interruption at age 2 years.
Baby baby
Contraception and HIV
The big story at last year’s CROI was the Mississippi Baby: born to a mother with high viral load, she was started on ART by 31 h of age; she had
Findings of the VOICE study (abstr 847) suggest that injectable contraception increases the risk of HIV in women with herpes simplex virus 2 (HSV2). Among 3167 women using injectable contraception in this observational study, 1801 exclusively used depot medroxyprogesterone acetate (DMPA), 1109 noresthisterone enanthate (NETEN), and 257 used both. 246 women acquired HIV (6·6 infections per 100 person years); women taking DMPA were more likely to be older, be married, and have children, less likely to have multiple sex partners, and had a higher incidence of HSV2 at baseline. Among women using DMPA the rate was 7·86 per 100 person years and among those using NET-EN the rate was 5·34 per 100 person years—unadjusted hazard ratio
Dong L Zou/Wikimedia Commons
“Our best estimate is it’s zero”, said Alison Rodger when asked what the risk was of a person with undetectable viral load passing HIV onto a sex partner. Rodger and colleagues presented the PARTNER study (abstr 153), which enrolled serodiscordant couples who had sex without condoms, in which the infected partner was on antiretroviral therapy (ART) and had a viral load of less than 200 copies per mL. Among 757 couples (282 men who have sex with men), 894 couple years of followup, and almost 45 000 sex acts without condoms not one phylogentically linked HIV transmission occurred. Any acquired infections seemed to have been transmitted during extrapartner sex. The study is ongoing, and Jens Lundgren told press that he hoped that by 2017 they would have sufficient data to confirm zero risk of transmission, having recruited an additional 450 couples of men who have sex with men across 75 clinics in Europe.
The 21st CROI was held in Boston, MA, USA, March 3–6, 2014
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1·31 (95% CI 0·96–1·79, p=0·092), HR adjusted for age and marital status 1·44 (1·05–1·98, p=0·024). Women with HSV2 infection taking DMPA had twice the risk of HIV acquisition compared with those with HSV2 taking NET-EN. Lisa Noguchi emphasised that women need both effective strategies for contraception and HIV prevention.
Three strikes, HCV is out The highly anticipated final results of the SYNERGY trial (abstr 27) were presented by Anita Kohli on behalf of a group of National Institutes of Health investigators. Interferon-free and ribavirin-free combination oral antiviral therapy that added a third directly acting antiviral agent (DAA) was shown to be as safe and effective at treating hepatitis C virus (HCV) infection in as little as 6 weeks. Three arms were compared: a sofosbuvir plus ledipasvir arm, and then two arms that included an additional DAA (either GS9667 or GS9451, each of which target different points in the HCV lifecycle). Notably, the patients included in the study were all treatment-naive and from a representative and historically difficult-to-treat population—largely African American, with high viral loads and predominantly genotype 1a. These findings suggest that effective, tolerable, and shorter duration treatment for HCV is within reach, not only in the USA but worldwide.
Longer, faster, better, stronger? In the past 3 years, pre-exposure prophylaxis (PrEP) has dominated the conversation about HIV prevention; however, adherence to the available pill-based regimens is poor. Taking a page from the birth control playbook, researchers have looked to long-lasting injectable compounds as an alternative. In two landmark studies researchers www.thelancet.com/infection Vol 14 April 2014
Newsdesk
from the US Centers for Disease Control and Prevention investigated novel compounds to protect against SHIV in macaques. Chasity Andrews and coworkers presented results suggesting that a low-level dose of the integrase inhibitor GSK1265744 (approximately 800 mg in human) successfully protected animals against transmission after repeated rectal challenge (abstr 39). In a similar study looking at protection under repeated vaginal challenge, Jessica Radzio (Atlanta, GA, USA) and others showed that administration of GSK744 (equivalent to 400 mg in human) fully protected the 12 study animals (abstr 40).
Single-dosing for children? Continuing the theme of improving adherence, there is a push for effective single-pill daily regimens for HIV. Adults can take once daily doses of the protease inhibitor lopinavir boosted with ritonavir, but current recommendations
for children are limited to twicedaily administration. In the international, randomised controlled non-inferiority trial KONCERT (abstr 74), the pharmacokinetics of lopinavir/ritonavir were examined in a group of 173 children with low viral loads (50 copies per mL) who were on the standard twice-daily dose. Half of the children were switched to a single dose and both groups were followed up for 48 weeks. Hermione Lyall presented data showing that, although there was little difference in clinical endpoints (CD4 counts, metabolic indices), viral rebound was more common with the single dose (14%) than with the twice-daily dose (8%). On the basis of these findings, switching to oncedaily lopinavir/ritonavir was not recommended for children.
Losing bone loss
T cell count. On the downside, it can also bring about rapid bone mineral density (BMD) loss—an estimated 2–6% reduction within the first 2 years of ART. Results from a substudy of the AIDS Clinical Trials Group A5280 study looked at supplementation with high-dose vitamin D (4000 IUD) plus 1000 mg of calcium carbonate as a way to stave off BMD in people beginning an efavirenz regimen (abstr 133). From baseline to 48 weeks, BMD loss in hip in the placebo group was about double that of the vitamin D plus calcium supplementation group (3·19% vs 1·46%; p<0·001). Edgar Overton, who presented the results of the trial, stressed that these findings represented a safe and low-cost intervention that could slow the progression of bone loss. Future work in this area could focus on lower doses of vitamin D and longer follow-up.
Initiating ART in patients with HIV can bring swift changes in viral load and
Rebecca Cooney, Peter Hayward
Infectious disease surveillance update Polio-like disease in the USA A rare polio-like disease has been identified in California, USA, with about 20 patients affected in the past 18 months. The disease is characterised by acute flaccid paralysis, in which patients quickly and permanently lose muscle function in an arm or leg, with some experiencing respiratory symptoms before paralysis begins. Researchers have suggested the disease might be caused by enterovirus 68. Investigators will present a report of five early cases at the American Academy of Neurology annual meeting in Philadelphia, PA, USA (April 26 to May 3).
H5N1 in Cambodia Two children in Cambodia died from avian influenza A H5N1 infection in the first week of March. A 3-year-old boy from a village outside Phnom Penh died in the National Paediatric Hospital on March 2. An 11-year-old boy admitted www.thelancet.com/infection Vol 14 April 2014
to Phnom Penh’s Kantha Bopha Hospital with suspected H5N1 influenza infection died on March 7; another boy admitted in the same week was said to be in a stable condition on March 9. All confirmed cases of H5N1 in Cambodia this year have been in children with a history of exposure to poultry. As of Feb 25, 658 laboratory-confirmed cases of H5N1 infection and 388 deaths worldwide have been reported to WHO from 15 countries.
Salmonella in Australia More than 200 people became ill with salmonellosis in February after eating foods containing raw eggs from two restaurants in Victoria, Australia. On March 3, the Chief Health Officer reported that the source of the outbreak had been identified as Green Eggs farm near Ararat (VIC). The Department of Environment and Primary Industries has restricted the sale of eggs from
the farm until cleaning and hygiene measures have been taken. People are being urged to use eggs from the supplier in cooked foods only.
Measles in the Mediterranean An outbreak of measles has been reported among the crew of the cruise ship Costa Pacifica. On Feb 27 the ship arrived in Civitavecchia, Italy, from Palma de Mallorca, Spain; Italian health authorities reported that members of the crew had possible symptoms of the disease. The next day nine individuals were admitted to hospital in Rome. Two further probable cases were identified when the ship arrived in Savona on March 1. According to the European Centre for Disease Prevention and Control, “the apparent high attack rate among the crew suggests a low vaccine coverage in this group”.
For more on the polio-like disease in the USA see http:// healthier.stanfordchildrens.org/ q-rare-polio-like-diseaseemerges-california/ For more on H5N1 influenza in Cambodia see http://www. phnompenhpost.com/national/ boy-11-dies-avian-flu-hospitaldoctor For more on salmonella in Australia see http://www. theguardian.com/world/2014/ mar/03/salmonella-outbreak-invictoria-prompts-raw-eggwarning For more on measles in the Mediterranean see http://www. ecdc.europa.eu/en/publications/ Publications/rapid-riskassessment-measles-cruise-shipMediterranean-5-March-2014. pdf
Neil Bennet 277
Highlights from the 21st CROI Scientists and clinicians gathered in Boston for the annual Conference on Retroviruses and Opportunistic Infections (CROI). Rebecca Cooney and Peter Hayward report. No virus, no risk?
detectable virus in the days after birth, but was subsequently virologically suppressed. She was lost to care, but despite treatment cessation viral load did not rebound. Deborah Persaud and colleagues reported that at age 39 months, 21 months after stopping ART, the child has undetectable viral load; despite low-level persistence of proviral DNA in circulating peripheral blood mononuclear cells, no replicationcompetent DNA was detected. Persaud also reported another child born to a mother with very high viral load and started on nevirapine by 4 h of age. HIV infection was confirmed by peripheral blood HIV DNA at 4 h of life, HIV RNA at 36 h, and CSF virus detection at 6 days. However, at 9 months the child has undetectable virus or viral DNA (abstr 75LB). The IMPAACT trial network now aims to recruit prospectively 54 infants being born to mothers with high viral loads who will start very early treatment, with a planned treatment interruption at age 2 years.
Baby baby
Contraception and HIV
The big story at last year’s CROI was the Mississippi Baby: born to a mother with high viral load, she was started on ART by 31 h of age; she had
Findings of the VOICE study (abstr 847) suggest that injectable contraception increases the risk of HIV in women with herpes simplex virus 2 (HSV2). Among 3167 women using injectable contraception in this observational study, 1801 exclusively used depot medroxyprogesterone acetate (DMPA), 1109 noresthisterone enanthate (NETEN), and 257 used both. 246 women acquired HIV (6·6 infections per 100 person years); women taking DMPA were more likely to be older, be married, and have children, less likely to have multiple sex partners, and had a higher incidence of HSV2 at baseline. Among women using DMPA the rate was 7·86 per 100 person years and among those using NET-EN the rate was 5·34 per 100 person years—unadjusted hazard ratio
Dong L Zou/Wikimedia Commons
“Our best estimate is it’s zero”, said Alison Rodger when asked what the risk was of a person with undetectable viral load passing HIV onto a sex partner. Rodger and colleagues presented the PARTNER study (abstr 153), which enrolled serodiscordant couples who had sex without condoms, in which the infected partner was on antiretroviral therapy (ART) and had a viral load of less than 200 copies per mL. Among 757 couples (282 men who have sex with men), 894 couple years of followup, and almost 45 000 sex acts without condoms not one phylogentically linked HIV transmission occurred. Any acquired infections seemed to have been transmitted during extrapartner sex. The study is ongoing, and Jens Lundgren told press that he hoped that by 2017 they would have sufficient data to confirm zero risk of transmission, having recruited an additional 450 couples of men who have sex with men across 75 clinics in Europe.
The 21st CROI was held in Boston, MA, USA, March 3–6, 2014
276
1·31 (95% CI 0·96–1·79, p=0·092), HR adjusted for age and marital status 1·44 (1·05–1·98, p=0·024). Women with HSV2 infection taking DMPA had twice the risk of HIV acquisition compared with those with HSV2 taking NET-EN. Lisa Noguchi emphasised that women need both effective strategies for contraception and HIV prevention.
Three strikes, HCV is out The highly anticipated final results of the SYNERGY trial (abstr 27) were presented by Anita Kohli on behalf of a group of National Institutes of Health investigators. Interferon-free and ribavirin-free combination oral antiviral therapy that added a third directly acting antiviral agent (DAA) was shown to be as safe and effective at treating hepatitis C virus (HCV) infection in as little as 6 weeks. Three arms were compared: a sofosbuvir plus ledipasvir arm, and then two arms that included an additional DAA (either GS9667 or GS9451, each of which target different points in the HCV lifecycle). Notably, the patients included in the study were all treatment-naive and from a representative and historically difficult-to-treat population—largely African American, with high viral loads and predominantly genotype 1a. These findings suggest that effective, tolerable, and shorter duration treatment for HCV is within reach, not only in the USA but worldwide.
Longer, faster, better, stronger? In the past 3 years, pre-exposure prophylaxis (PrEP) has dominated the conversation about HIV prevention; however, adherence to the available pill-based regimens is poor. Taking a page from the birth control playbook, researchers have looked to long-lasting injectable compounds as an alternative. In two landmark studies researchers www.thelancet.com/infection Vol 14 April 2014
Newsdesk
from the US Centers for Disease Control and Prevention investigated novel compounds to protect against SHIV in macaques. Chasity Andrews and coworkers presented results suggesting that a low-level dose of the integrase inhibitor GSK1265744 (approximately 800 mg in human) successfully protected animals against transmission after repeated rectal challenge (abstr 39). In a similar study looking at protection under repeated vaginal challenge, Jessica Radzio (Atlanta, GA, USA) and others showed that administration of GSK744 (equivalent to 400 mg in human) fully protected the 12 study animals (abstr 40).
Single-dosing for children? Continuing the theme of improving adherence, there is a push for effective single-pill daily regimens for HIV. Adults can take once daily doses of the protease inhibitor lopinavir boosted with ritonavir, but current recommendations
for children are limited to twicedaily administration. In the international, randomised controlled non-inferiority trial KONCERT (abstr 74), the pharmacokinetics of lopinavir/ritonavir were examined in a group of 173 children with low viral loads (50 copies per mL) who were on the standard twice-daily dose. Half of the children were switched to a single dose and both groups were followed up for 48 weeks. Hermione Lyall presented data showing that, although there was little difference in clinical endpoints (CD4 counts, metabolic indices), viral rebound was more common with the single dose (14%) than with the twice-daily dose (8%). On the basis of these findings, switching to oncedaily lopinavir/ritonavir was not recommended for children.
Losing bone loss
T cell count. On the downside, it can also bring about rapid bone mineral density (BMD) loss—an estimated 2–6% reduction within the first 2 years of ART. Results from a substudy of the AIDS Clinical Trials Group A5280 study looked at supplementation with high-dose vitamin D (4000 IUD) plus 1000 mg of calcium carbonate as a way to stave off BMD in people beginning an efavirenz regimen (abstr 133). From baseline to 48 weeks, BMD loss in hip in the placebo group was about double that of the vitamin D plus calcium supplementation group (3·19% vs 1·46%; p<0·001). Edgar Overton, who presented the results of the trial, stressed that these findings represented a safe and low-cost intervention that could slow the progression of bone loss. Future work in this area could focus on lower doses of vitamin D and longer follow-up.
Initiating ART in patients with HIV can bring swift changes in viral load and
Rebecca Cooney, Peter Hayward
Infectious disease surveillance update Polio-like disease in the USA A rare polio-like disease has been identified in California, USA, with about 20 patients affected in the past 18 months. The disease is characterised by acute flaccid paralysis, in which patients quickly and permanently lose muscle function in an arm or leg, with some experiencing respiratory symptoms before paralysis begins. Researchers have suggested the disease might be caused by enterovirus 68. Investigators will present a report of five early cases at the American Academy of Neurology annual meeting in Philadelphia, PA, USA (April 26 to May 3).
H5N1 in Cambodia Two children in Cambodia died from avian influenza A H5N1 infection in the first week of March. A 3-year-old boy from a village outside Phnom Penh died in the National Paediatric Hospital on March 2. An 11-year-old boy admitted www.thelancet.com/infection Vol 14 April 2014
to Phnom Penh’s Kantha Bopha Hospital with suspected H5N1 influenza infection died on March 7; another boy admitted in the same week was said to be in a stable condition on March 9. All confirmed cases of H5N1 in Cambodia this year have been in children with a history of exposure to poultry. As of Feb 25, 658 laboratory-confirmed cases of H5N1 infection and 388 deaths worldwide have been reported to WHO from 15 countries.
Salmonella in Australia More than 200 people became ill with salmonellosis in February after eating foods containing raw eggs from two restaurants in Victoria, Australia. On March 3, the Chief Health Officer reported that the source of the outbreak had been identified as Green Eggs farm near Ararat (VIC). The Department of Environment and Primary Industries has restricted the sale of eggs from
the farm until cleaning and hygiene measures have been taken. People are being urged to use eggs from the supplier in cooked foods only.
Measles in the Mediterranean An outbreak of measles has been reported among the crew of the cruise ship Costa Pacifica. On Feb 27 the ship arrived in Civitavecchia, Italy, from Palma de Mallorca, Spain; Italian health authorities reported that members of the crew had possible symptoms of the disease. The next day nine individuals were admitted to hospital in Rome. Two further probable cases were identified when the ship arrived in Savona on March 1. According to the European Centre for Disease Prevention and Control, “the apparent high attack rate among the crew suggests a low vaccine coverage in this group”.
For more on the polio-like disease in the USA see http:// healthier.stanfordchildrens.org/ q-rare-polio-like-diseaseemerges-california/ For more on H5N1 influenza in Cambodia see http://www. phnompenhpost.com/national/ boy-11-dies-avian-flu-hospitaldoctor For more on salmonella in Australia see http://www. theguardian.com/world/2014/ mar/03/salmonella-outbreak-invictoria-prompts-raw-eggwarning For more on measles in the Mediterranean see http://www. ecdc.europa.eu/en/publications/ Publications/rapid-riskassessment-measles-cruise-shipMediterranean-5-March-2014. pdf
Neil Bennet 277