Title: IAS feedback: news drugs and prevention studies African Treatment Advocacy Training
1 IAS feedback news drugs and prevention studiesAfrican Treatment Advocacy Training
20 September 2007
2 Aim to understand drugs only work on active cells different targets some targets have no drugs HIV life cycle 3 (No Transcript) 4 Timeline for developing a drug Phase 3 efficacy and safety Phase 1 single dose HIV-negative Phase 4 long-term safety identify compounds/molecules 10yrs Pre-clinical Animal and test tube Phase 2 dose finding HIV-positive Expanded access (EAP) / named-patient programmes (NPP) 5 Feedback from 4th IAS Conference
PrEP for conceiving a baby
Circumcision sub-study - washing after sex
6 Maraviroc MERIT study CCR5 inhibitor naïve vs EFV non-inferior at 48wk by lt400 but NOT lt50 (69 vs 65) fewer pts lt50 with baseline VL gt100000 copies/mL (67 vs 60) CD4 count 170 vs 144 - favoured maraviroc Similar side effects - more malignancies with EFV lipids ok driven by Northern vs Southern differences FDA approved (6 August 2007) Tropism questions - 50 experienced pts fail screening test only sensitive when gt5-10 dual/mixed X4/R5 change between screening BL How and when is best use for this drug Saag M et al. Abstract WESS104. 7 Raltegravir Protocol 004 study integrase inhibitor naïve vs EFV 24 week responses continue to week 48 similar efficacy (viral load) to EFV at 48wks (all doses) - approx 88 lt50 copies/mL similar CD4 increases similar tolerability (less CNS 0 nightmares) rapid early viral load drop (clinical significance) similar resistance (3 5 vs 1 still very low numbers but XRx) better lipids (TC LDL TG but similar reductions in TCHDL ratio) continued strong results important to use with other active drugs Markowitz M et al. Abs TUAB104. 8 RTG vs EFV Viral Decay
RAL taken twice daily EFV taken once daily both with TFV/3TC.
Incidence at least 5 in any treatment group all severity levels included.
10 Effect on Serum Lipids
Total cholesterol LDL-cholesterol triglycerides not increased by raltegravir
Mean change from baseline (mg/dL) at week 48
Efavirenz Raltegravir RAL vs EFV Mean Change Baseline Mean Mean Change Baseline Mean Plt0.001 20.7 168.7 -2.3 165.9 Cholesterol P0.016 3.0 108.9 -7.5 103.8 LDL-C P0.068 49.5 127.3 -1.0 131.8 Triglycerides P0.52 -0.47 4.72 -0.59 4.59 TotalHDL ratio All raltegravir dose groups combined. 11 Etravirine (ETV TMC-125 NNRTI) DUET study 3-class experienced All received darunavir/r OBR /- ETV/placebo ETV produced increased viral load decrease (20-30 more) 3 mutations from 13 (DUET) decreased response V90I A98G L100I K101E/P V106I V179D/F Y181C/I/V G190A/S K103N not associated with ETV resistance Single/dual mutations present in 20 NNRTI-experienced pts (n1700) but in lt2 (ANRS Cotte et al) confirms activity in people with NNRTI resistance caution that needs supported regimen (active PI and/or nukes) Katlama C et al. Abs WESS204.2. Mills A et al. Abs WESS204 12 rilpivirine (TMC-278 NNRTI) 48 wk dose finding study treatment naïve vs EFV All received TDF/FTC or AZT/3TC TMC (3 doses) or EFV 90 pts each group Similar viral load decrease (80 lt50 c/mL wk48) Similar change in CD4 ( 125 c/mm3) Similar lipids Potential alternative to efavirenz
Pozniak A et al. Abstract WEPEA105
Ruxrungtham K et al. Abstract TUAB105.
Additional supportive data that circumcision is a protective intervention for sexually active men in high prevalence populations
Consistent washing was not associated with a reduction HIV-incidence and early washing with an increased risk
Circumcision didnt show protection in population studies of gay men and MSM in Australia
PrEP with TDF used in sero-different couples with treatment and lt50 copies VL and urine LH peak
Oral session on circumcision available online http//www.ias2007.org/pag/PSession.aspxs 55 14 Pre-exposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child Objectives To reduce risk-taking behavior in HIV-discordant couples (male HIV-pos.) willing to conceive a child. Methods HIV-discordant couples expressing the desire to conceive a child received a standardized risk reduction counseling including LH-peak measurement and pre-exposure prophylaxis with tenofovir 36 and 12 h before intercourse. Couples were either included after having previously been counseled for artificial insemination with processed semen and quit the program for any reason or after referral through their HIV-physician. Results Twenty-two couples were admitted for risk reduction counseling. All male partners have been under a fully suppressive antiretroviral treatment. Six couples admitted that they had previously tried to conceive by unprotected intercourse. Twenty-one couples decided to use the proposed risk reduction strategy with timed intercourse and TDF-pre-exposure-prophylaxis. Pregnancy rates were high with more than 50 pregnancies achieved after 3 cycles (11/21). In 15/21 female partners got pregnant after up to 10 attempts. All women tested negative for HIV-antibodies 3 months after the last exposure. Conclusions The true number of HIV-discordant couples who practice unprotected sex to conceive is most likely underestimated. The risk of transmission in a couple with a fully treated male partner is low and can further be reduced by timed intercourse and a short pre-exposure prophylaxis with tenofovir. The pregnancy rates of natural conception are substantially higher than with artificial reproduction techniques (40 in our program). Vernazza P. Abstract MoPDC01. 15 PrEP for serodifferent couples and pregnancy 21 HIV-different couples. All male partners 50 copies/mL for at least three months. Semen viral load was undetectable in all men (though only tested at the start of the study). Urine LH-peak measurement to determine ovulation and pre-exposure prophylaxis tenofovir 36 and 12 hours before intercourse gt 50 pregnancies achieved after 3 cycles (11/21) and 70 women (15/21) became pregnant after up to 10 attempts. All women tested negative for HIV-antibodies 3 months after the last exposure. pregnancy rates of natural conception in this study were substantially higher than by artificial reproduction techniques (40) Vernazza P. Abstract MoPDC01. 16 Washing after sex
Post-coital penile cleansing was common
Post-coital penile cleansing as practiced in the rural population of Rakai did not protect from male HIV acquisition among uncircumcised men
Washing less than 10 minutes after intercourse may increase HIV risk relative to delayed cleansing
Washing with water had higher risk than dry cloth
Washing-alone is associated with a non-significant increase in HIV-incidence among uncircumcised men
Makumbi FE et al. Abs WEAC1LB 17 Results -1 Adjusted IRR of HIV incidence by post-coital cleansing Adjusted for Condom use marital status age non-marital partnerships alcohol use with sex perceived partners HIV status sex freq number of sexual partners Consistent washing was not associated with a reduction HIV-incidence Makumbi FE et al. Abs WEAC1LB 18 Results -2 Adjusted IRR of HIV incidence by duration from sex to penile washing among men who reported washing with all partners Chi-sq for trend7.14 p0.0076 HIV-incidence was significantly lower if washing was delayed gt 10 minutes after sexual intercourse Makumbi FE et al. Abs WEAC1LB 19 Results -3 Adjusted IRR of HIV incidence by post-coital penile cleansing methods
Chi-sq for trend3.62 p0.0554 Increasing degree of wetness (assessed by self-reported washing) was associated with a borderline significant trend of increasing risk of HIV-acquisition Makumbi FE et al. Abs WEAC1LB 20 www.i-Base.info simon.collins_at_i-Base.org.uk Thank you
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