2012 UPDATE ON AIDS

1. 2012 UPDATE ON AIDS Seja Joyce Jackson, APRN, AAHIVS Central AHEC at Burgdorf Clinic Hartford, CT 03/21/12

2. GLOBAL EPIDEMIOLOGY 33.4 million people living with HIV – Worldwide 22.4 million are in sub Saharan Africa. Only 40% of HIV + people know their status. Only 5 million on therapy – 10 million waiting. There will be 2.7 million new infections each year. There will be 2 million deaths this year. The majority of transmissions are via heterosexual sex.

3. US EPIDEMIOLOGY • In the US approximately 1.2 million people are living with HIV. • One in 5 (20%) are unaware that they are positive. • MSM of color fastest growing group though caucasian MSM are still the largest absolute number. • This also corresponds with a large increase in syphilis cases for MSM. • AA women are next most newly diagnosed group. • Also see increase in new cases over 50 years old. • IVDU have the least new cases. • In the US the peaks of infection are in San Francisco, LA, Miami, Washington DC, Boston, New York.

6. CONNECTICUT EPIDEMIOLOGY The peaks of HIV incidence in CT are still in Bridgeport, Hartford and New Haven. A significant increase in numbers of young, MSM of color. Substance use still a significant factor.

8. PREVENTION Should we be treating all HIV infected people? An article in the Lancet used a mathematical model to suggest that “Test and Treat” regardless of stage or CD4, could decrease new HIV cases by 95% in 10 years. Similar questions remain re sustainability, resources, pill fatigue, resistance, side effects. What about personal choice or will this be more like TB, where treatment is mandated?

9. PREVENTION BY BEHAVIOR CHANGE HIV Specialists have been advocating behavior change for over 2 decades. This has not been successful. Target groups – not getting or accepting the message – WHY NOT? Young MSM of color are now most at risk. Impact of being young, alienated, closeted, stigmatized. Men on the down-low. Condom fatigue, access, use of substances all contribute to failure. No memory of early AIDS epidemic. “Not my disease”. Believe that AIDS is “not so bad” just take a pill every day.

10. PREVENTION THE BEST MEDICINE – OR NOT? PreP: using medication, including microbicides and oral medications to prevent transmission. CDC has approved daily Truvada for PreP in MSM. Intermittent PreP is not approved (though many lay people do it this way). There are no studies on this. Must screen for HIV first & be sure the person is negative. A maximum 90 day supply should be provided. Testing for other STI’s and HIV should be done routinely. Creatinine level testing should be done routinely.

11. PrePMYSTERIES With Pre-Exposure Prophylaxis (PreP) come many unanswered issues. Is it safe to give ARV to healthy people? What if they don’t come for indicated blood work or STI screenings? What about resistance development? Will this affect future med choices? Is this affordable? (Insurance usually doesn’t cover prevention meds). Will healthy people take more risks if they are on PreP? (note the studies on microbides).

12. ANY EXCUSE NOT TO USE CONDOMS? New studies on a 1% Tenofovir based vaginal antimicrobicide are encouraging. In the CAPRISA 004 study women had approx 47% effectiveness at 6-18 months for HIV prevention. This decreased to 39% at 30 months. Mostly due to decreased adherence. May also have activity against HSV 2. Study showed 51% less new HSV2 infection in women using the gel. A new study of 71 women in NYC, with a h/o substance use showed low condom use to begin with and then even less if they used a microbicide (no matter how low the effectiveness was supposed to be). This is called condom migration (using them less over time).

13. MORE MICROBICIDE RESEARCH A separate study compared oral and gel forms of Tenofovir. The daily use of gel use resulted in 100x higher vaginal tissue concentration. The daily use of the tablet had 10x higher blood concentration. American women liked the oral tablet best. African women were equally divided, though some liked the gel because they said it enhanced sexual pleasure.

14. POTENTIAL USES FOR MICROBICIDES Initial findings presented at CROI 2011 indicate that Tenofovir gel use could reduce the risk of transmission from anal sex. Tissue biopsies were taken from HIV negative men and women who used Tenofovir gel microbicide anally were then exposed to HIV virus. Analysis showed those samples with the microbicide use were less likely to develop HIV.

15. MICROBICIDES • The rectal lining is only 1 cell thick while the vaginal lining has multiple layers which may contribute to the risk of anal infection being approximately 20x greater than vaginal. • Samples from participants who took oral Tenofovir did not provide protection.

16. CIRCUMCISION CONTROVERSY A study presented at CROI 2011 suggested that circumcision reduced HIV 50-60% in the short term (24 weeks) and in a follow up after 5 years reduction was up to 73%. Primarily felt to be due to reducing Genital Ulcer Disease, which enhances HIV transmisssion. A second study from Kenya found similar results but found that HSV2 rates were unchanged and syphilis rates were actually higher. Rates for all GUD (chanchroid, LGV< etc) was 48% lower.

17. SCREENING Guidelines for cervical cancer screening have changed but not those for HIV+ women. As the HIV+ population ages and we identify more HIV+ persons over 50 we will undoubtedly see an increase in all cancers. HIV experts, along with ID, hepatologists, & colorectal specialists may be significant in changing some of the screening guidelines for people with HIV and/or Hepatitis C.

18. SCREENING Other than cervical cancer and anal Paps screening guidelines for PwHIV are mostly the same as the general population. No randomized trials for screening for anal cancer with Paps, despite that the incidence of SCC is 10-50x > for HIV+MSM and 7-28x > for women with HIV.

19. ANAL PAPS • Anal Paps are easy to do, painless, inexpensive. • Some expert groups suggest anal paps for all HIV+ MSM and women w hx of anal sex every year (change from 2-3 yrs). • Abnormal Paps should be followed up by colorectal specialists who may do biopsies or other tests.

20. LET THE SUNSHINE IN By 2015 over 50% of PWHIV will be over 50! Highest risk for osteoporosis is for HIV+ people on medication, then HIV+ people with no medication and then HIV- people. Also for any group over 50. Tenofovir may be associated with significant bone loss (more so than other meds). ASSERT study showed that there is an initial loss but then there is some recovery. In SMART study bone density continued to decrease for 4 years after stopping meds. Supplements: Vitamin D and Calcium

21. NON AIDS CANCERS on the RISE Rates for non-AIDS Cancers in people with HIV are increasing. Cancers with viral etiologies have the highest rates. (Anal cancer-HPV, hepatocellular cancer-HBV, HCV). Hodgkin’s and oropharyngeal cancer are on the rise. Lung cancer is modestly increased. Epithelial cancer rates are generally the same as the general population. Reasons for these increases not known. KS and Lymphoma are significantly decreased.

22. HPV VACCINE The HPV vaccine (Guardasil) now has been approved for use in women and men ages 9-26. Data was so good the FDA stopped the trial early. The vaccine includes HPV type 6,11,16,18 protection. A different vaccine protects against only 2 types. Infection with oncogenic HPV can cause cancers of the penis, anus, head and neck in men as well as cervical cancers in women. The quadrivalent vaccine protects against these strains. Other strains may still be present and cause genital/oral warts. HIV+ men, particularly, MSM are more at risk for cancer development.

23. THE PENDULUM SWINGS New recommendations for when to start HAART. New data on adverse effects of uncontrolled viremia on morbidity and mortality. Issue of chronic inflamation and immune activation with untreated HIV. Relevance to persons with hepatic, renal, cardiovascular, OI’s. New drugs available with fewer pills, less side effects. Importance for HIV transmission prevention.

24. SO, WHEN DO WE START??? When the person is ready! Need to educate people, assess readiness, give resources to assist to optimal adherence. When other issues such as OI’s, decreasing T cells, multiple partners, unsafe sex deem it necessary. Discuss with the person at multiple opportunities. Goal is to keep viremia down and T cells up. T Cells below 350 definitely, 350-500 offer therapy, 500 & above discuss risks/benefits and offer therapy.

25. MEDICATIONS Recent new FDA analysis finds that Abacavir is not a cardiac risk. New studies suggest EKG’s for all people on Atazanavir and Saquinavir, looking for baseline EKG abnormalities (prolonged QTc). This may turn out to be a problem for all PI’s (a class effect). Kaletra liquid should not be used with newborns or infants due to high alcohol content.

26. MEDICATIONS • New once a day combination pill – Complera (Truvada, Rilpivirine (Edurant) – NRTI and NNRTI. Ok for use in pregnancy. • The new QUAD pill is hopefully to be introduced in the next 12-16 months. This is a 4 in 1 pill including a non Ritonavir (Norvir) booster (Cobicstat) and a new integrase inhibitor (Elvitegravir) . • Also new meds for Hepatitis C that are Protease Inhibitor pills are now available, however, they can not be used in conjunction with HIV meds, particularly PI’s. There is an interaction which decreases the effectiveness of both.

27. HERE COMES THE FUTURE ! Gene therapy: Most amazing of the potential new therapies for HIV. Studies being conducted a U Penn, and in Germany. Now in CA, FL, NY as well. Potential to have virus suppressed without having to take daily medication. Defining “Cure” as “permanent remission of disease (and it’s consequences) in the absence of therapy.

28. CCR5- Mutated STEM CELLS – CURE??? CCR5 is one of the most common paths for HIV to enter the CD4 cell. Individuals with only the CCR5 gene 32 allele appear to naturally resist infection with CCR5 strains of HIV (lacking cell surface expression of CCR%) From a report based in Germany: In 2007 an HIV infected pt had a stem cell transplant with CCR5 32/32 cells for treatment of acute myeloid leukemia. HAART was stopped that day. Patient had a 2nd transplant 13 months later. This pt’s T cell numbers returned to normal and HIV remains undetectable to this date without medication. Usually, after stem cell therapy HIV rebounds (as there are more T cells for the virus to grab onto). The patient still remains vulnerable to infection with X4 virus.

29. CURE??? Findings continue to be encouraging. Must be duplicated in other patients. Practical approach to cure? Not according to Dr Paul Sax, well-known HIV expert from Harvard. “The upfront toxicity and risk of death are too high, especially given how safe antiretroviral therapy is now” Paul Sax Also the proportion of people who have the needed gene as potential donors is very small (esp in non-Caucasians).

30. HOPE !!! The studies at U Penn and in Germany are testing different strategies and therapies than we have now. Though study population is small results: encouraging. U Penn researchers are proposing to investigate using high dose chemotherapy to eradicate the HIV reservoir. German researchers continue with stem cell research. The fascinating part of this is the paradigm shift in thinking about a cure for HIV infection. “Many think a cure for HIV is impossible, but they also thought treatment could not be successful for a retrovirus 15 years ago”John Bartlett, MD, Johns Hopkins University.

31. VACCINES, THE FINAL FRONTIER Still in trials. No successful prevention vaccine at this time. Some HIV Vaccine research is shifting focus from prevention to changing the nature of the infection, according to Dr Anthony Faucci, from NIAID. Researchers realized that even while you are infected with the virus you can get reexposed/reinfected at the same time.

32. MORE ON VACCINES • Research began to shift from a prevention vaccine to one that makes the illness less lethal, even benign. An example would be to help lower viral loads. This would mean less transmission. So far, that approach has not been successful. • Also there might be differences in the transmitting virus and the chronic replicating virus. Working with this could help vaccine development, though not as yet.

33. CHALLENGES – OLD & NEW If you don’t like the weather – wait a minute. Much of HIV care information changes rapidly – about every 6 months we learn new things. Chronic disease or still a stigma? Waiting for the “Cure”– will it be gene therapy? Vaccines? Medications? PreP? Will the public grow tired of HIV?

34. CHALLENGES • Caring for an older population with comorbid conditions as well as a young population with adolescent beliefs/behaviors. • Identifying more new cases through “opt-out” testing –will we have the providers and the resources? • Need for more HIV trained providers as the aging provider population retires.

35. SUGGESTIONS Whenever possible use the “Team Approach” with the patient at the center of the team. Remember to address the whole person not just the disease. Information is a powerful tool – stay informed. Keep a POSITIVE attitude – things have gotten better! Have fun at what you do. Encourage other health care providers to consider HIV as an area within which to work.