Standard Medications for HIV-AIDS: There are four types of HIV medications: 1) NRTIs (Nucleoside Reverse Transcriptase Inhibitors)=$208-$286/mo.=abacavir(ABC-Ziagen), Didanosine (ddl-Videx), lamivudine (3TC-Epivir), stavudine (d4T-Zerit), zalcitabine (ddC-Hivid), Zidovudine (ZDV-Retrovir); 2) Nucleotide Reverse Transcriptase Inhibitors=Adefovir(Preveon); 3) Non-nucleoside Reverse Transcriptase Inhibitors=$229-394/mo.=delavirdine(Rescriptor), efavirenz (EFV-Sustiva), nevirapine (Viramune). 4) Protease Inhibitors=$450-668/mo=indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase, Fortovase).  Almost all patients take several medications.

New Protease Inhibitor Lopinavir-ritonavir Found Superior: At the end of the 24- and 48-week periods, more patients using the new lopinavir-ritonavir combination were able to suppress the amount of virus in their blood to under 50 copies per milliliter, a level that doctors and researchers aim for when starting therapy. Ritonavir is a booster which slows lopinavir from being metabolized. Boosting of protease inhibitors is a whole new concept in HIV therapy. Current levels barely enough. No patients with virologic failure on the lopinavir-ritonavir combination showed evidence of resistance to the drug compared to the nelfinavir group, in which 33 per cent of failing patients developed resistance. Toronto, 6/27/02 NEJM

Increasing Medicine Resistance: In 1996–97, none of the patients were infected with nnRTI-resistant virus. In 2000–01, 13.2% nnRTI-resistant virus. Transmission of virus resistant to protease inhibitors (PI) also increased. PIs are another class of drugs that have received much attention in the last several years for their potency. Infection with PI-resistant virus increased from 2.5 percent of patients in 1996–97 to 7.7 percent of patients in 2000–01. 27% resistant to at least one drug. JAMA 7/10/02. In 1997 just 3.3% of patients were resistant to all classes of antiretroviral. In 2000 United States study found over a quarter of patients were resistant to all three classes of antiretroviral drug. Dr Anton Pozniak, a consultant at the Chelsea and Westminster Hospital, speaking at the disclosure of the results, said that levels of drug resistance are likely to reach 42% by 2005. BMJ 7/13/02

$34,000/yr to Treat One Patient with AIDS: 2002 average U.S. patient cost.  Most of the cost of treatment is paid by the taxpayer and very little is paid for by the patients.

CD4 200 Cutoff: 12,000 adult patients analyzed. Below 200 it is too late for meds to control disease, but above 200 the survival rate is much higher. Eggers, Lancet 7/12/02

Diabetes Increased 200% in Men Treated for HIV: 563 HIV-negative and 544 HIV-positive men, 423 of whom were receiving HAART. The incidence rates of hyperglycemia and diabetes were determined in 618 men with a fasting plasma glucose of 105 mg/dL or lower and no history of diabetes mellitus or use of diabetes medications. At baseline, 14% of the HIV-infected men had diabetes, compared with 5% of the HIV-negative men. After controlling for age and body mass index,  HIV-infected men on HAART had 1.8 times the risk of development diabetes or pre-diabetes of HIV-negative men. The risk of diabetes was 3.1 times greater in the HIV-infected men on HAART than in the HIV-negative men. TT Brown, Johns Hopkins, 2/11/04

Diarrhea in HIV Patients Dramatically Reduced by Probiotic Yeast: S. boulardii was used to treat 33 HIV patients with chronic diarrhea. In these double-blind studies, 56% of patients receiving S. boulardii had resolution of diarrhea compared with only 9% of patients receiving placebo. Saint-Marc T., Rossello-Prats L., Touraine J. L. Efficacy of Saccharomyces boulardii in the treatment of diarrhea in AIDS (letter). Ann. Med. Intern. 1991;142:64-65. Ed: Other studies comparing lactobacillus yogurt to S. boulardii suggests that yogurt would do just as well, but at a lower cost.

Diarrhea from HIV Med Helped by Glutamine: In a 25-patient DB PC crossover study, HIV-infected patients with nelfinavir-associated diarrhea for >1 month were randomized to receive L-glutamine 30 g/day or placebo for 10 days. Diarrhea was measured on a scale ranging from grade 0 (no diarrhea) to grade 4 (severe diarrhea, > 7 stools/day). Diarrhea scores were glutamine 0.762 vs. placebo 1.850, p <.01. Quality of life scores favored glutamine 1.48 vs. -2.19, p <.017.  L-glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. Huffman FG, Walgren ME. Florida International University, HIV Clin Trials. 2003 Sep-Oct;4(5):324-9

Diarrhea from HIV Helped by Glutamine: In a 41 patient DB PC study, glutamine both decreased diarrhea and increased antiretroviral drug levels suggesting that it helps with treatment as well. Clin Infect Dis 6/15/2004;38:1764-1770

Entry Inhibitors Promising: T-20, a sub-type of entry inhibitors known as fusion inhibitors. first quarter of 2003, following a fast-track review. SCH-C from Schering-Plough by blocking the CCR5 receptor, or doorway, that is found on the immune system's T-cells. GSK developing integrase inhibitor S-1360 that is designed to block HIV's capacity to insert its genes into a cell's normal DNA. 7/10/02

Fatigue: Testosterone Helped Fatigue But Not Depression in HIV/AIDs: Fluoxetine Helped Depression a Little: In a 123-man 8-week DB PC trials of testosterone (up to 400 mg IM testosterone cypionate biweekly), fluoxetine (up to 60 mg/d), or double placebo, ninety men completed the trial. In intention-to-treat analyses, mood response rates were 54%, 47%, and 44% for fluoxetine, testosterone, and placebo. Among completers, mood response rates were 70%, 57%, and 53%, respectively; in neither analysis were differences between treatments statistically significant. In contrast, testosterone was superior to fluoxetine and placebo for completers regarding fatigue. In intention-to-treat analysis, response rates were 39%, 56%, and 42% for fluoxetine, testosterone, and placebo, respectively, and for study completers, 41%, 63%, and 52%, respectively, (P < 0.05), Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. Rabkin JG, Wagner GJ, McElhiney MC, Rabkin R, Lin SH. New York State Psychiatric Institute. J Clin Psychopharmacol. 2004 Aug;24(4):379-85

GB Virus Type C Infection Might Be Protective: Men infected with both HIV and GB virus type C (GBV-C) for at least five years were three times less likely to die than HIV-positive men who did not have GBV-C. GBV-C, a virus that infects white blood cells, does not cause any known disease. It is transmitted through blood and blood products, and many people carry the virus, some for up to 40 years. Eleven years after contracting HIV, 75% of the men who had GBV-C in blood samples 5 years apart were still alive. Of the men who did not have GBV-C in either blood sample, only 39% survived for 11 years. The men who had GBV-C in their first blood sample but not in the second had the greatest risk of dying. Only 16% of them were still living after 11 years. GBV-C might inhibit HIV from growing in human cells. Johns Hopkins University, JT Stapleton et al. Persistent GB virus type C infection and survival in HIV-infected men. New England J Medicine 350(10):981-90 (3/4/2004).

HIV Infectability and Pre-Term Labor Might be Decreased by Yogurt: Complications arising from bacterial vaginosis (BV) include increased risk of sexually transmitted diseases including human immunodeficiency virus and elevated risk of preterm birth (PTB). Antibiotics have not been optimally effective and have failed to reduce the incidence of PTB. The absence of lactobacilli in the vagina, a specific feature of BV, suggests the use of yogurt can restore the normal flora and improve the chances of having a healthy term pregnancy. The potential for probiotics to prevent bacterial vaginosis and preterm labor. Reid G, Bocking A. Am J Obstet Gynecol. 2003 Oct;189(4):1202-8; Ed: Several other studies have reported evidence that bacterial vaginosis increases the risk of getting infected with HIV. While this does not appear to be a major risk factor, it is one very easily treated.

Melatonin Reduced in HIV Infected and Drops with Progression: In HIV-1 infection, an impairment of interleukin-12 (IL-12) production precedes a switch from a T-helper 1 (Th1) to a T-helper 2 (Th2) stage of cellular immunity. Melatonin, the main hormone produced by the pineal gland, seems to promote a Th1 response by increasing the production of IL-12. In a study of 77 anti-HIV-1-positive subjects and 20 healthy controls, melatonin were significantly lower in HIV-1-infected individuals in comparison with controls (p < 0.001). Within the HIV-1-seropositive group, mean melatonin and IL-12 concentrations were significantly lower in patients in CDC stage C, as compared with patients in CDC stages B and A (p < 0.01). Reduction of serum melatonin levels in HIV-1-infected individuals' parallel disease progression: correlation with serum interleukin-12 levels. Nunnari G, Nigro L, et al. Thomas Jefferson University. Infection. 2003 Dec;31(6):379-82

Multiple Simultaneous Long-Term Relationships Increase AIDS in Africa: Africans do not have more sexual relationships that Americans or Europeans. However, both African men and women are much more likely to have one or more simultaneous long-term relationships in addition to their primary one whereas in the U.S. and Europe, men and women tend to have serial relationships, but just one at a time. These simultaneous long-term relationships dramatically alter the speed at which HIV can spread through a population. One factor that aids this spread is that a person who has been recently infected with HIV may be as much as 100 times more likely to transmit the virus than someone who has been infected for a longer time since once antibodies develop, they dramatically reduce the number of HIV virus particles in the blood until AIDS eventually overwhelms the body.  The emphasis on condoms just doesn't work.  They fail to prevent infection 10% of the time due to breakage or human error.  Uganda was successful in significantly lowering its adult AIDS rate by crusading against simultaneous relationships and reducing the rate of such relationships from 35% of the adult population to 15%. New Scientist. 2004.

Muscle Wasting Helped by HMB, Arginine, Glutamine: Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). A mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day was not associated with any adverse indicators of health. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p < .05) when compared with placebo.  Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. Rathmacher JA, Nissen S, Panton L, Clark RH, Eubanks May P, Barber AE, D'Olimpio J, Abumrad NN.  Iowa State University, JPEN J Parenter Enteral Nutr. 2004 Mar-Apr;28(2):65-75

N-acetyl-L-cysteine No Benefit as Add-on on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment. Treitinger A, Spada C, et al. Federal University of Santa Catarina. Braz J Infect Dis. 2004 Oct;8(5):363-71.

Protease-Inhibitor Triple Regimes Better: In a meta-analysis using indirect comparisons of clinical trials comparing three drug regimens based on two nucleoside reverse transcriptase inhibitors (NRTIs) and either a protease inhibitor or an NNRTI with two drug regimens (two NRTIs), 14 trials, totalling 6785 patients, were identified. Most patients had been exposed to an NRTI and had advanced immunodeficiency at baseline; 1096 progressed to AIDS or died. Seven trials assessed protease inhibitors based triple regimens and seven assessed NNRTI based triple regimens (nevirapine or delavirdine). Triple therapy was more effective than dual therapy. The effect was pronounced for protease inhibitor based regimens (odds ratio 0.49) but non-significant for NNRTI based regimens (0.90). BMJ 1/30/04.

Selenium Helped Anxiety in HIV+: In a 12-month DB PC study of 63 HIV+ drug users given selenium 200 mcg/day, 69% had elevated anxiety and 25% moderate depression (BDI over 20). These were not related to current drug abuse, HIV treatment or viral load. Those on selenium had a major increase in vigor (p,.001). and less state and trait anxiety (p=.03). Depression was not affected by selenium. After controlling for antiretroviral therapy, CD4 decline, and education, anxiety was six times more common in the placebo group. Psychological burden in the era of HAART: impact of selenium therapy. Shor-Posner G, Lecusay R, et al. University of Miami. Int J Psychiatry Med. 2003;33(1):55-69

Selenium: HIV Shedding Increased 200% in Low Selenium: Kenya study of 319 HIV+ women. Selenium deficiency is associated with shedding of HIV-1--infected cells in the female genital tract. Baeten JM, Mostad SB, Hughes MP, Overbaugh J, Bankson DD, Mandaliya K, Ndinya-Achola JO, Bwayo JJ, Kreiss JK. J Acquir Immune Defic Syndr 2001 Apr 1;26(4):360-4

Selenium: HIV Hospitalizations Decreased 35% by Selenium: Hospitalizations declined from 157 before the trial to 103 during the 2-year study of selenium in a DB PC trial of 186 HIV+ patients with half given 200microg/d (RR = 0.38; p =.002) and the percent of hospitalizations due to infection/100 patients also decreased for those receiving selenium (p =.01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p =.001). Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants. Burbano X, Miguez-Burbano MJ, McCollister K, Zhang G, Rodriguez A, Ruiz P, Lecusay R, Shor-Posner G. HIV Clin Trials 2002 Nov-Dec;3(6):483-91

Selenium May Help HIV Patients: Of 949 HIV-1-infected Tanzanian women who were pregnant, over the 5.7-year follow-up, 306 died. Lower plasma selenium levels were significantly associated with an increased risk of mortality (P= 0.01). Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania . Kupka R, Msamanga GI, et al. Harvard. J Nutr. 2004 Oct;134(10):2556-60

Sinusitis: Guaifenesin Helps: In a 23-patient DB PC study of chronic rhinosinusitis in HIV positive patients, guaifenesin, a mucolytic, at 2400 mg per day did help decrease nasal congestion and thin the post-nasal drainage. The role of guaifenesin in the treatment of sinonasal disease in patients infected with the human immunodeficiency virus (HIV). Wawrose SF, Tami TA, Amoils CP. Laryngoscope. 1992 Nov;102(11):1225-8. Ed: Numerous European studies have shown that mucolytics have a small, positive effect in decreasing the frequently of recurrent episodes of acute bronchitis in chronic bronchitis patients.

Vaginitis in HIV Patients Prevented as Well with Lactobacillus acidophilus as with Clotrimazole: In a randomized 21-month DB PC study of 164 HIV patients, weekly intravaginal clotrimazole and L. acidophilus tablet each markedly decreased yeast infections with the clotrimazole doing non-significantly better. Yale. Evaluation of two self-care treatments for prevention of vaginal candidiasis in women with HIV. Williams AB, Yu C, Tashima K, Burgess J, Danvers K. J Assoc Nurses AIDS Care. 2001 Jul-Aug;12(4):51-7. Ed: Eating yogurt daily would probably have a similar effect but at the same time accomplish many other useful purposes.

Vitamins: HIV Patients May Need Vitamin D Supplementation: In a lab study using intact cells, HIV-protease inhibitors (a standard medication in HIV treatment) markedly suppress the activities of 25- and 1alpha-hydroxylase, which are critical in 1,25(OH) D synthesis, while exerting mild inhibition of 24-hydroxylase, responsible for 1,25(OH) D catabolism. Defective 1,25(OH) D production caused by protease inhibitors could contribute to the bone demineralization in HIV patients. Washington Univ. AIDS. 2003 Mar 7;17(4):513-20. Osteoporosis occurs much more often to HAART HIV patients than in the normal population at the same age.  This is especially true for those on protease inhibitors, 21% of whom had osteoporosis. Q J Nucl Med. 2004 Mar;48(1):39-48

Vitamins: Multivitamin Supplements Delay the Progression to AIDS and Death: In a DB PC study of 1078 pregnant women infected with HIV comparing daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease, the median follow-up with respect to survival was 71 months. Of those given multivitamins, 31% survived vs. 25% on placebo ( P=0.04). Multivitamins also resulted in significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads. Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined. A randomized trial of multivitamin supplements and HIV disease progression and mortality. Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ. Harvard. N Engl J Med. 2004 Jul 1;351(1):23-32

Vitamin A Bad During HIV Pregnancy: In a Harvard DB PC study of vitamins A, B, C, and E, significantly more women who received vitamin A had detectable levels of HIV-1 in CVL (74.8%), compared with those who did not receive vitamin A (65.1%) (P=.04). Multivitamin B-complex, C, and E had no effect on the risk of viral shedding. This raises concern about the use of vitamin A supplements by HIV-1-infected women. Effect of prenatal vitamin supplementation on lower-genital levels of HIV type 1 and interleukin type 1 beta at 36 weeks of gestation. Fawzi W, Msamanga G, Antelman G, Xu C, Hertzmark E, Spiegelman D, Hunter D, Anderson D. Clin Infect Dis. 2004 Mar 1;38(5):716-22

Vitamin D Deficiency and Osteoporosis Very Common: In 44 HIV victims, non-African-Americans were more likely to have osteopenia or osteoporosis (59%) compared to African-Americans (26%) (p = 0.09). The prevalence of vitamin D insufficiency (< 34 ng/ml) and elevated i-PTH (>65 pg/ml) was 79% and 20%, respectively. Ethnic variations in the prevalence of metabolic bone disease among HIV-positive patients with lipodystrophy. Curtis JR, et al. University of Alabama. AIDS Res Hum Retrovirus 2006 Feb;22(2):125-31.

Yogurt: HIV Infectability and Pre-Term Labor Might be Decreased by Yogurt: Complications arising from bacterial vaginosis (BV) include increased risk of sexually transmitted diseases including human immunodeficiency virus and elevated risk of preterm birth (PTB). Antibiotics have not been optimally effective and have failed to reduce the incidence of PTB. The absence of lactobacilli in the vagina, a specific feature of BV, suggests the use of yogurt can restore the normal flora and improve the chances of having a healthy term pregnancy. The potential for probiotics to prevent bacterial vaginosis and preterm labor. Reid G, Bocking A. Am J Obstet Gynecol. 2003 Oct;189(4):1202-8; Ed: Several other studies have reported evidence that bacterial vaginosis increases the risk of getting infected with HIV. While this does not appear to be a major risk factor, it is one very easily treated.

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com

Email: [email protected]