The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
...
AIDS Rounds Sept 13, 2013
Is it the End of HIV Transmission
(at the End of the Cascade)?
Sheldon Morris M.D., M.P.H.
Introduction
 The test and treat strategy is the highly touted as the
best hope for controlling the HIV epidemic.
1) Is H...
Diagnoses of HIV Infection among Adolescents and Young
Adults Aged 13–24 Years, by Transmission Category
2008–2011—United ...
Diagnoses of HIV Infection among Adolescents and Young
Adults Aged 13–24 Years, by Transmission Category
2008–2011—United ...
Marks G. AIDS. 2006;20:1447-1450.
Marks G. AIDS. 2006;20:1447-1450.
Marks G. AIDS. 2006;20:1447-1450.
Marks G. AIDS. 2006;20:1447-1450.
CCTG 592: a randomized controlled
study of a internet intervention for HIV
infected MSM to reduce STIs
 Enrolled 181 MSM ...
CCTG 592: Baseline Analysis
 Any detectable viral load (>75 copies/ ml) was found in
18%
 High level detectable viral lo...
CCTG 592: MSM on Stable ART
CCTG 592: HIV-infected MSM on ART
 Complete viral suppression among MSM on ART was
found in only 82%
 Factors associated...
CNICS: Geospatial Analysis
 891 San Diego CNICS subjects were included if they had
one patient reported outcome (PRO) que...
CNICS: Geospatial Analysis
Individual characteristics
significantly associated
with an increased risk
(p<0.02) of HRTB inc...
Rates of Risk Behaviors HIV-infected Patients in Care by CBG
Bayesian
estimate of
HRTB per
1000
population
Haubrich CROI 2...
CCTG 592: What about MSM on ART and Suppressed?
 Among MSM on stable ART and have suppressed virus
in plasma how many are...
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Status New infections
Aware (ART)
Aware (no ART)
Unaware
Awareness of HIV Serostat...
People Living With HIV
(1,039,000-1,185,000)
New Sexual infections/Year
(~32,000)
Percent
Marks G. AIDS. 2006;20:1447-1450...
Sheth JAIDS 2009
 After initiation of ART 12/25 (48%) had at least one visit with detectable sVL
 Shedders had higher bV...
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Politch AIDS 2012
Ghosn IAS 2013
 157x 2 samples 4 wks apart, 74% BPVL ND with ultrasensitive assay
 23/304 (7.6%) – 5 x 1st visit; 14 x 2...
Politch AIDS 2013
 Of the 101 men, 18% had HIV RNA in blood [median HIV-RNA copy
number/ml (range): 560 (80–6.4 x 105)], ...
 HIV-infected MSM (n=114)
 CCTG 592
 ON ART (median 882 days, IQR: 406-1725)
 Median CD4+ T-cells: 580 cells/ml
 HIV ...
CCTG 592: MSM on Suppressive ART
Gianella CID 2013
CCTG 592: MSM on Suppressive ART
Gianella CID 2013
CCTG 592: MSM on Suppressive ART
Gianella CID 2013
** In sub-analysis with HIV RNA in blood <50copies/ml high-level CMV
re...
What could be done to reduce risk of
transmission on ART?
People Living With HIV
(1,039,000-1,185,000)
New Sexual infections/Year
(~32,000)
Percent
Marks G. AIDS. 2006;20:1447-1450...
People Living With HIV
(1,039,000-1,185,000)
New Sexual infections/Year
(~32,000)
Percent
Marks G. AIDS. 2006;20:1447-1450...
Chrakraborty 2001
 Probability of transmission of HIV 3/10000 for semen viral load<1000 copies/ml
Sheth 2009
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Attia 2009
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Morris 2013
If we estimate a 92% reduction in HIV-transmission during A...
Morris 2013
 average of two unprotected anal sex acts per HIV-infected MSM per month with
serodiscordant partners (CCTG 5...
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Osborne 2013
Does ART Regimen Matter?
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Osborne 2013
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Osborne 2013
Grant RM, et al. N Engl J Med. 2010;363:2587-2599.
Future Interventions for Semen Shedding
 Good ART management: Start ea...
March 18, 2013
UCSD AVRC
Questions
Barriers of HIV Prevention through Treatment
Barriers of HIV Prevention through Treatment
Barriers of HIV Prevention through Treatment
Barriers of HIV Prevention through Treatment
Barriers of HIV Prevention through Treatment
Barriers of HIV Prevention through Treatment
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Barriers of HIV Prevention through Treatment

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Sheldon Morris, MD, of UC San Diego AntiViral Research Center, presents "Barriers of HIV Prevention through Treatment"

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Barriers of HIV Prevention through Treatment

  1. 1. The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
  2. 2. AIDS Rounds Sept 13, 2013 Is it the End of HIV Transmission (at the End of the Cascade)? Sheldon Morris M.D., M.P.H.
  3. 3. Introduction  The test and treat strategy is the highly touted as the best hope for controlling the HIV epidemic. 1) Is HIV declining? 1) Where are we in the achieving high rates of HIV treatment and what are the barriers to success? 1) If we get individuals onto durable ART is there still going to be transmission? How much?
  4. 4. Diagnoses of HIV Infection among Adolescents and Young Adults Aged 13–24 Years, by Transmission Category 2008–2011—United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.
  5. 5. Diagnoses of HIV Infection among Adolescents and Young Adults Aged 13–24 Years, by Transmission Category 2008–2011—United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.
  6. 6. Marks G. AIDS. 2006;20:1447-1450.
  7. 7. Marks G. AIDS. 2006;20:1447-1450.
  8. 8. Marks G. AIDS. 2006;20:1447-1450.
  9. 9. Marks G. AIDS. 2006;20:1447-1450.
  10. 10. CCTG 592: a randomized controlled study of a internet intervention for HIV infected MSM to reduce STIs  Enrolled 181 MSM November 2010-July 2012 at UCSD, USC and Harbor-UCLA  Final visit of last participant in Aug 2013  Outcome with be Risk reduction intervention versus control survey alone for incident STI any site (syphilis, CT/GC in throat, rectum or urethra)
  11. 11. CCTG 592: Baseline Analysis  Any detectable viral load (>75 copies/ ml) was found in 18%  High level detectable viral load (>1000 copies/ml) was found in 9%  Unprotected anal sex with a potentially serodiscordant and any detectable viral load occurred in 13%
  12. 12. CCTG 592: MSM on Stable ART
  13. 13. CCTG 592: HIV-infected MSM on ART  Complete viral suppression among MSM on ART was found in only 82%  Factors associated at risk of transmission of HIV among MSM on ART based on detectable plasma viral load were black race, low CD4 count, METH use
  14. 14. CNICS: Geospatial Analysis  891 San Diego CNICS subjects were included if they had one patient reported outcome (PRO) questionnaire in 2011.  Geocoding to the census block group (CBG) level  49% HRTB was defined as any of the following in the past 6 months: unprotected anal or vaginal sex; sex after alcohol or drugs; sharing injection drug use equipment; more than 2 partners; and sex with HIV negative or unknown partner. Haubrich CROI 2013
  15. 15. CNICS: Geospatial Analysis Individual characteristics significantly associated with an increased risk (p<0.02) of HRTB included: CBG rates of HRTB were significantly higher ( all p<0.05) in communities with:  younger age  Fewer visits to HIV care  higher nadir CD4  No AIDS diagnosis  current substance use  higher current CD4  male gender  absence of a current mental health diagnosis  lower income  greater percentage males  higher education  shorter distance to care and higher population  Moran’s global I statistic indicated significant global clustering of HRTB (p<0.001) and cluster ‘hot-spots’ were identified by Kuldorff’s scan statistic. Haubrich CROI 2013
  16. 16. Rates of Risk Behaviors HIV-infected Patients in Care by CBG Bayesian estimate of HRTB per 1000 population Haubrich CROI 2013
  17. 17. CCTG 592: What about MSM on ART and Suppressed?  Among MSM on stable ART and have suppressed virus in plasma how many are still shedding HIV in their semen?  What are the factors associated with detectable for HIV in semen?
  18. 18. 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Status New infections Aware (ART) Aware (no ART) Unaware Awareness of HIV Serostatus: Estimates of Transmission 25% 65% Marks G. AIDS. 2006;20:1447-1450. 20% ?? New Infections/Year (~32,000) People Living With HIV
  19. 19. People Living With HIV (1,039,000-1,185,000) New Sexual infections/Year (~32,000) Percent Marks G. AIDS. 2006;20:1447-1450. Rates of HIV Shedding in Semen on ART Trial Pop. HIV shedding Comments Ghosn 2013 157 MSM on ART 23/304 (7.6%) 5 1st visit 14 2nd visit 2 both visits 2 samples 4 wks apart 74% BPVL ND with ultrasensitive assay 145 copies (40-1475) Gianella 2013 114 MSM on ART 11/114 (9.6%) 6/100 (6.0%) when BPVL ND 1 sample per subject Semen plasma HIV RNA 2.1 log10 copies (1.7- 2.5) Politch 2012 101 MSM on ART 30/101 (30%) detectable HIV RNA and/or DNA in semen Semen HIV RNA or DNA 18% had HIV RNA in blood - median 560 (80– 650, 000) Sheth 2009 25 MSM initiating ART 48% had HIV in semen at least once 16.4% of all BPVL ND Blood and semen were collected at weeks 0, 2, 4, 8, 12, 16, 20 and 24. Marcellin 2008 145 men on ART in assisted reproduction 16/264 (6.1%) 7/232 (3.0%) when BPVL ND 1-6 samples per subject median HIV-1 RNA in semen 1770 copies/ml
  20. 20. Sheth JAIDS 2009  After initiation of ART 12/25 (48%) had at least one visit with detectable sVL  Shedders had higher bVL of 4.65 log10 RNA copies/ml (vs. 4.50; P.0.86) and lower baseline CD4 T cell count 195 vs. 230/ml (p=0.97)  Baseline sVL was 10-fold higher in those with isolated semen shedding than in those without detectable isolated shedding (median 4.42 vs. 3.41 log10 RNA copies/ml; P.0.03)  In 13 STI-free, long-term ART-treated men, with an undetectable bVL for median 82 months (range: 48–216 months), isolated semen HIV RNA shedding was detected in four of 13 participants (31%; median 564 RNA copies/ml, range: 336–828 copies/ml) Sheth 2009
  21. 21. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Politch AIDS 2012
  22. 22. Ghosn IAS 2013  157x 2 samples 4 wks apart, 74% BPVL ND with ultrasensitive assay  23/304 (7.6%) – 5 x 1st visit; 14 x 2nd visit; 2 x both visits  20.5% had an STI (syphilis, gardnerella, ureaplasma, gonorrhea, mycoplasma, chlamydia, HSV2) but this was not associated with shedding  Factors associated wth shedding included: CD4 554-735 compared to lower or higher, presence of PBMC HIV-DNA >318 per 10 x6 PBMCs.
  23. 23. Politch AIDS 2013  Of the 101 men, 18% had HIV RNA in blood [median HIV-RNA copy number/ml (range): 560 (80–6.4 x 105)], and 30% had HIV RNA and/or DNA in semen  Of the 30 men with HIV in semen, 17 had CF HIV-RNA, 17 had CA HIV-RNA and 5 had CA HIV-DNA  Detection of HIV in semen was also associated with elevated concentrations of several other seminal inflammatory markers: TNF-a, IL-6, IL-8, and SLPI.
  24. 24.  HIV-infected MSM (n=114)  CCTG 592  ON ART (median 882 days, IQR: 406-1725)  Median CD4+ T-cells: 580 cells/ml  HIV RNA levels in blood <500copies/ml  100 subjects HIV RNA <50copiem/ml Determinants of HIV Shedding in Semen on ART Gianella CID 2013
  25. 25. CCTG 592: MSM on Suppressive ART Gianella CID 2013
  26. 26. CCTG 592: MSM on Suppressive ART Gianella CID 2013
  27. 27. CCTG 592: MSM on Suppressive ART Gianella CID 2013 ** In sub-analysis with HIV RNA in blood <50copies/ml high-level CMV replication was the only predictor of detectable HIV RNA in semen
  28. 28. What could be done to reduce risk of transmission on ART?
  29. 29. People Living With HIV (1,039,000-1,185,000) New Sexual infections/Year (~32,000) Percent Marks G. AIDS. 2006;20:1447-1450. Heterosexual HIV Transmission After ART Initiation in Discordant Couples • Partners for the Prevention of HSV/HIV Transmission study – Prospective cohort analysis of discordant couples (n=3381) – 7 African countries • HIV-infected partners starting HAART (n=349) – Genetically linked HIV transmission (n=103) • Follow-up – Up to 24 months Donnell D, et al. Lancet. 2010;375:2092-2098. HIV Incidence HIVIncidence (per100-person-years) 2.24 (1.84-2.72) 0.37 (0.09-2.04) HIV Partner Had Initiated HAART No Yes 92% Reduction
  30. 30. People Living With HIV (1,039,000-1,185,000) New Sexual infections/Year (~32,000) Percent Marks G. AIDS. 2006;20:1447-1450. HPTN 052 • Median follow-up: 1.7 years – HIV RNA <400 copies/mL • Early ART: 90% • Delayed ART: 93% • Linked HIV transmission to HIV- negative partner (n=39) – Early therapy (n=1) • 0.1 per 100 person-years – Delayed therapy (n=27) • 1.7 per 100 person-years • Early ART that suppressed HIV RNA led to a 96% reduction of sexual transmission of HIV in serodiscordant couples CumulativeProbability 0 1 2 3 4 5 Linked HIV Transmission Early ART Delayed ART Cohen M, et al. N Engl J Med. 2011;Jul 18. [Epub ahead of print]. Hosseinipour MC, et al. 6th IAS Conference. Rome, 2011. Abstract MoAX0104. Years HR: 0.04 (95% CI 0.01-0.27) (P<0.001) *Transmission occurred within 90 days after the index initiated antiretroviral therapy.
  31. 31. Chrakraborty 2001  Probability of transmission of HIV 3/10000 for semen viral load<1000 copies/ml Sheth 2009
  32. 32. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Attia 2009
  33. 33. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Morris 2013 If we estimate a 92% reduction in HIV-transmission during ART to the summary estimated risk of heterosexual transmission of 0.008 = 0.0007. If couples had sex on all three days the monthly cumulative probability of conception would be 0.23 [calculated as 0.084+(1-0.084)*0.086+(1- 0.079)*0.081], while the risk of transmitting HIV would be 0.002.
  34. 34. Morris 2013  average of two unprotected anal sex acts per HIV-infected MSM per month with serodiscordant partners (CCTG 592)  probability of transmission of 0.00136 per act (92% reduction from 0.017)  Estimating 442,000 HIV-infected MSM living in the U.S. (CDC 2009)  If 59% on ART = 260,000 MSM on ART in the U.S.  Estimated sexually active MSM at 85%  approximately 7,000 transmissions in the U.S. related to MSM on ART Sheth 2009 Estimating HIV Transmissions from MSM on ART
  35. 35. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Osborne 2013 Does ART Regimen Matter?
  36. 36. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Osborne 2013
  37. 37. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Osborne 2013
  38. 38. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Future Interventions for Semen Shedding  Good ART management: Start early, maximize adherence  Are some regimens better than others?  CMV suppression?
  39. 39. March 18, 2013 UCSD AVRC
  40. 40. Questions

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