ARC ("AIDS-related complex") -- still a useful distinction

Under the old nomenclature, unexplained fever, weight loss, diarrhea, fatigue, night sweats of greater than three month's duration, in a person with evidence of HIV infection is called AIDS-related complex (ARC).

Often patients with ARC are troubled with minor infections, especially candidiasis, cryptosporidiosis, bad herpes simplex and/or zoster, hairy leukoplakia, tinea pedis ("athlete's foot"), tinea cruris ("crotch-rot"), others. Lymph nodes are usually enlarged.

Anatomic pathology of HIV infection

You will learn what the various infections and lymphomas look like in AIDS soon enough, and Kaposi's "sarcoma" has been described above.

Even in the absence of infections or cancer, AIDS victims suffer profound depletion of their lymphoid tissues, and also generalized wasting of body tissues, especially muscle (cachexia).

{23350} AIDS, atrophy of lymphoid tissue (trust me that this was a lymph node)
{05258} AIDS cachexia

In some tissues, patches of cells may be found undergoing apoptosis, usually a marker for cell-mediated cytolysis. (See Am. J. Surg. Path. 10: 531, 1986.)

"Bystander apoptosis" is now well-studied, and seems to result from infected T-cells with upregulated fas-ligand/CD95, which triggers the fas apoptosis trigger on the surfaces of neighboring cells. This may well account for much of the wasting syndrome and the destruction of uninfected T-cells (Virology 285: 181, 2001; AIDS 15: 957, 2001; Clin. Exp . Imm. 122: 364, 2000, many others).

For the original autopsy series of AIDS victims, read Arch. Pathol. 109: 737, 1985, Lancet 2: 85, 1988. For the most recent large series, see Arch. Path. Lab. Med. 126: 182, 2002. Taiwan's pathologists document that autopsy remains the gold standard, and that opportunitstic infections are often missed in life (J. Micro. 39: 310, 2006). The usual precautions in handling tissues seem to protect pathologists and pathology students against AIDS.

{20228} end-stage lymph node, AIDS; this used to be a lymph node, but almost all the lymphocytes are gone

HIV lymphadenopathy Yutaka Tsutsumi MD

The lymphadenopathy of ARC and persistent generalized lymphadenopathy resembles that of other viral diseases.

There is florid hyperplasia of the germinal centers, and other nonspecific reactive changes in the nodes (debris, new vessels, etc., etc. -- Am. J. Surg. Path. 11: 94, 1987).

HIV testing

Since only about 70% of people in the US who are HIV-positive know it (i.e., about a quarter-million don't know), offering to test is very important -- especially because people who know they are positive supposedly will be more careful with others.

Growing the virus is difficult, PCR is costly, and the usual lab screen is to look for anti-HIV antibodies in the blood.

The classic "screening test" is an ELISA ("enzyme-linked immunosorbent assay") procedure; it's usually positive by 6-8 weeks, but can take as long as 6 months or even longer. Today's ELISA's detect both p24 and HIV-1 (including subtype O) and HIV-2. Immunofluorescent assays for p24 supposedly turn positive earlier than the antibody. Today's rapid antibody tests for office use are very convenient; positives do need follow-up with Western blot or immunofluorescence, and PCR for viral load is the backup.

"Positives" are confirmed using a "Western blot" procedure and PCR.

Uncle Sam tests his army for HIV for only $2.50 per soldier (not bad, NEJM 32: 963, 1995).

Beware: Rare AIDS patients never seroconvert (J. Inf. Dis. 175: 955, 1997).

Blood banks, of course, do PCR on all units. Think about just ordering a PCR if you suspect the acute HIV infection syndrome. The virus is usually demonstrable in the blood in about 7 days after exposure, and peaks at 3 weeks (NEJM 356: 2073, 2007).

Probably it is good public health policy to include PCR testing in ALL HIV screening, at least those at high risk, since you'll pick up the 4% that are antibody-negative (mostly the acute infections, which are very contagious: NEJM 352: 1873, 2005; there are rare false-positive PCR's).

Today, anonymous testing is widely available, and as a result, people are getting diagnosed much earlier (JAMA 280: 1416, 1998).

Mail-in home HIV test uses a blood spot. It's remarkably accurate: Br. Med. J. 312: 1317, 1996; Arch. Int. Med. 157: 309, 1997. OraSure (mouth juice) HIV assay: JAMA 277: 254, 1997. Because of the benefits of HAART, started early, perhaps it's a good idea to ELISA everybody who's not abstinent or in a stable monogamous relationship every 3-5 years (NEJM 352: 586, 2005). More on this hard-to-answer topic: Ann. Int. Med. 145: 797, 2006.

At risk

AIDS spread in the same populations as hepatitis B did in the mid-20th century. Everyone remembers the four H's:

"Homosexual men" (MSM's):

Early in the epidemic, this was the main US group affected, thanks to the widespread practice of unprotected anal intercourse. Today, around half of HIV-positive patient being treated are MSM. See below.

Haitians:

As noted before, the virus first infected humans in Africa. HIV and AIDS abound in sub-Saharan Africa, in the "virus belt". See Science 226: 453, 1984. The African virus was probably acquired there by Haitian "migrant workers". American MSM's brought the infection to the US from Haiti ("Patient Zero" was the most famous, but there were many others).

The explanation for AIDS among the little Haitian boys given in Ann. Int. Med. 99: 877, 1984 (they were sex slaves... er, CSW's), has been quietly and generally accepted. Other infected Haitians received injections through unsterilized needles in a folk medical practice. Haitians without other risk factors are no longer considered a special risk group.

Update on HIV in Haiti: Science 313: 470, 2006 ("making headway under hellacious circumstances")

Heroin (and other recreational intravenous drug) users:

In some populations, as many as 64% of IV drug abusers (men and women) are now HIV positive (Br. Med. J. 300: 209, 1990). The statistics for New York City (JAMA 271: 191, 1994; the most recent I could find) stayed constant at around 50% during the peak years (ouch!), despite a shift from injecting to snorting heroin.

Blood on shared syringes readily transmits the virus. Users can prevent infection by rinsing syringes in hypochlorite ("Clorox") solution before sharing (unfortunately, this spoils rubber syringes).

Needle-exchange programs, where they have been implemented, represent a new twist in the "war on drugs". Politicians in the US mostly refuse to fund these (Lancet 349: 604, 1997; Am. J. Pub. Health. 90: 1385, 2000). On the "plus" side, they save money by preventing AIDS. And they don't seem to increase the amount of drug use (JAMA 271: 115, 1994) or crime (Am. J. Pub. Health. 90: 1933, 2000). On the "minus" side, politicians would be accused by their traditionally-minded constituents of endorsing drug abuse. Nobody wants the needle-exchange boutique next door (no kidding! Pub. Health. Reports 114: 439, 1999). Since intravenous drug abusers are not a popular group, there may be even darker reasons for voting down needle-exchange programs. Finally, even if the government doesn't fund these programs, they'll still exist. Most are non-funded and run by private donations; about half are frankly illegal and are either tolerated or underground (Am. J. Pub. Health 89: 43 1999). Vancouver now provides its junkies with a medically-supervised "safer injecting facility", without any obvious adverse impact on the community (CMAJ 175: 1399, 2006).

IV drug abuse, and sex with IV drug abusers, is was the most common way in which HIV is was transmitted in the U.S. during the 1990's (Neuro. Clin. 11: 605, 1993, others), and probably still is today, though the reappearance of the high-risk gay lifestyles has shifted the numbers back toward transmission by anal sex.

Hemophiliacs

Around 85% of patients with classic hemophilia (who received human-derived factor VIII) and hemophilia B (who receive factor IX) were positive in 1985 (Ann. Int. Med. 102: 753, 1985; Am. J. Med. 80: 345, 1986; NEJM 317: 1153, 1987). One percent of cases of AIDS have occurred in hemophiliacs.

Others at risk:

AIDS is a special risk for infants of HIV-positive mothers. The virus crosses the placenta, and may also be transmitted in milk. Review NEJM 332: 298, 1995.

Around 1.5% of U.S. women of childbearing age are now HIV-positive (JAMA 265: 1704, 1991). In 1990, 782 babies were born with HIV. Without prophylaxis, the risk of transmission to the baby is about 25%. The new drugs clearly help prevent transmission to the unborn child, and there are now laws requiring mothers-to-be to accept treatment. The new statistics show that AZT given to the pregnant mother cuts the rate of transmission from 19% to 3% (Br. Med. J. 324: 381, 2002).

Mothers can now be forced by law to comply, which upsets some people ("A woman's right to control her own body!") but not me. You, the physician, had better offer HIV tests to all pregnant women, but you had better NOT test if she refuses (Am. J. Ob. Gyn. 180: 259, 1999).

Prolonged rupture of the membranes (more than four hours) is, not surprisingly, a major risk: NEJM 334: 1617, 1996. C-sectioning HIV-positive moms seems to cut the risk in half: Lancet 343: 1464, 1994.

We now know that breast-feeding is indeed an efficient way of transmitting HIV: NEJM 325: 593, 1991. Providing formula instead results in a huge reduction in transmission: JAMA 283: 1167, 2000.

Anti-HIV IgA is likely to be present in milk; it does not protect the child (J. Ped. 149: 611, 2006).

In the poor nations, breast milk is clearly the best available food for newborns, both from the standpoint of nutrition and protection from infectious disease. Public health policy must weigh the 5-15% risk of the baby acquiring Mother's HIV infections against this fact.

The ongoing complexities are shown by the observation that non-breast-fed children in Botswana, while less likely to be infected with HIV, are more likely to die overall, simply because of malnutrition (JAMA 296: 794, 2006).

HIV-infected children typically become symptomatic within a year (NEJM 321: 1791, 1989), though some may remain healthy up to ten years. Around half of these children (who now number in the thousands) have obvious brain damage (NEJM 319: 889, 1988), and they are also at increased risk for bacterial infections (pneumococcus, H.'flu, salmonella, others) and the more traditional AIDS pathogens. AIDS in children: J. Pediatrics 114: 1, 1989.

Also at (relatively low) risk are female partners of infected men. This includes wives and CSW's.

As AIDS turns into a straight's disease (Am. J. Med. 102 S4A: 2, 1997), CSW's are important vectors of AIDS in the poor nations. In late-20th-century Thailand, an "economic miracle" was driven largely by government promotion of sexual services not available elsewhere, and the night-life was dominated by unhygienic, uncircumcised, lascivious young men. Most of the CSW's were HIV-positive, and at least 12% of the young men (especially the unhygienic, uncircumcised, lascivious ones) were infected (Lancet 343: 86, 1994; they catch it easily Lancet 343: 204, 1994). Thai men wise up and start using condoms to prevent HIV infection: NEJM 335: 297, 1996. Promoting condoms to the CSW's at the sexually-transmitted disease clinic in Zaire: Lancet 344: 246, 1994 (it helps).

Likewise, in America's crack houses, teenaged girls CSW themselves for drugs; 40% of these girls are HIV-positive (NEJM 331: 1422, 1994).

By contrast, English CSW's are almost all HIV-negative, and their customers (though not their boyfriends) use condoms regularly (Br. Med. J. 307: 356, 1993). The same is now true for CSW's throughout Western Europe, though CSW's coming to the area from the former Soviet bloc are likely to be HIV-positive because of needle drug use (Lancet 364: 1, 2004).

In the early days, one percent of AIDS cases were acquired by blood transfusions (JAMA 254: 770, 1985; perhaps 12,000 people were infected by transfusions before testing made the blood supply safe). If a person gets a unit of infected blood, the chance of contracting AIDS is around 95%.

* Hundreds of Americans were injected with material containing AIDS virus as part of the quack Bahamas cancer treatment (JAMA 254: 1139, 1985; JAMA 255: 505, 1986). AIDS from sloppy acupuncture technique: NEJM 320: 250 & 321: 1476, 1989.

* Thousands of Romanian infants were infected from moronic blood transfusions: Lancet 335: 595, 1990; Lancet 338: 645, 1991. Under the Ceausescu tyranny, physicians had few things that they could do, so they gave blood transfusions promiscuously.

The situation in sub-Saharan Africa is still a nightmare, but there are some hopeful developments. Update: Lancet 364: 1, 2004. AIDS is the major cause of young adult mortality throughout much of Africa (Sci Am. 282(5): 96, May 2000).

For inspiration, see the account in Acad. Med. 82: 812, 2007. Indiana Med partners with Kenya's medical schools to set up an effective AIDS prevention and treatment program.

In sub-Saharan Africa, sexual promiscuity of any sort is a risk factor. Explanations that have been put forward...

(1) Needles used in VD clinics and hospitals are not sterilized between patients (Lancet 2: 1018, 1985).

Unsafe medical injections caused outbreaks among children in Russia in 1988 and in Libya in 1998 (Int. J. STD 13: 152, 2002). Libya's response to this embarrassing revelation was to charge 5 Bulgarian nurses and a Palestinian physician with doing this intentionally. The Libyan government obtained confessions by torture, and condemned the six to death; they were freed in 2007 after Bulgaria paid extortion money to Ghadaffi. I am not making this up (Nature 430: 277, 2004; Br. Med. J. 328: 1153, 2004; Science 308: 184, 2005). Although the six health care workers were obviously innocent victims of Gaddafi's evil, even the WHO is now starting to talk about the likelihood that iatrogenically-spread HIV is common in Africa (Bull. WHO 80: 859, 2002; South Afr. Med. J. 94: 109, 2004).

In 2003, an activist popularized the notion that this is more important than sex, and even if this doesn't seem to be so, it's probably still happening at least sometimes (Nat. Med. 10: 44, 2004). The militant claim examined: Lancet 363: 82, 2004.

(2) Heterosexual anal intercourse is widely practiced here (Contraception Fertility & Sexuality 21: 145, 1993 -- the Paris-based African Medical Institute, Am. J. Epidem. 135: 593, 1992), both as a method of cheap birth control and because many cultures practice "female circumcision" (more about this later), causing fibrosis so that intromission is difficult;

(3) Other venereal diseases, with genital ulcers, notably chancroid, are prevalent here (a risk for both men and women: J. Inf. Dis. 163: 233, 1991; Arch. Int. Med. 154: 1391, 1994).

(4) The "AIDS belt" (see below), where 10% or more of adults are infected, corresponds very closely to the areas where men are uncircumcised: Sci. Am. 274(3): 62, March 1996.

In northwestern Africa, where most of the men are circumcised, the HIV epidemic has been far less severe. In Senegal, the epidemic is even described as "contained" (Lancet 364: 1, 2004; perhaps the fact that this might be the best-governed country in the AIDS belt also gives people hope for a better future and a reason to be careful).

Circumcision clearly protects a guy in the developed nations from catching AIDS from a woman: Urol. Clin. N.A. 22: 57, 1995; Arch. Int. Med. 154: 1391, 1994; Lancet 354: 1813, 1999; Lancet 355: 926, 2000; risk cut by 5/6 Lancet 363: 1039, 2004; Nat. Rev. Micro. 3: 914, 2005. This seems to be fully accepted in today's medical literature, and in fact, three African studies were stopped early for ethical reasons because the benefits were so obvious (J. Sex. Med. 4: 838, 2007). People are now talking about male circumcision being the reason for the relative rarity of AIDS in Islamic countries (Repro. Fert. Dev. 13: 405, 2001 was first; Lancet 364: 3, 2004). A prospective randomized study of male circumcision in rural Uganda shows about a 50% reduction, and not because circumcision changes behaviors (Lancet 369: 657, 2007). Almost identical results from rural Kenya: Lancet 369: 643, 2007. WHO's chief HIV/AIDS director Kevin de Cock comes out strongly in favor of circumcision to prevent AIDS: JAMA 297: 231, 2007 (* you already know that's his real name).

* The anti-circumcision movement has, to date, countered with much inflammatory, militant rhetoric but no counter-evidence; it would seem to me that they now bear the burden of proof, and men in the AIDS belt are now lining up to be circumcised.

(5) In much of Africa, the norm is "long-term concurrency" (i.e., a man has several girlfriends, a woman has several boyfriends) rather than "serial monogamy" as in the United States. Now, couples in "established relationships" don't always used condoms, here or there. And sex evidently happens much more often between couples there than here. (Hmmmm...) See Lancet 362: 4, 2004. "Transactional sex" (a new word for SW) seems to be driving the HIV epidemic in Accra, Ghana (AIDS 18: 917, 2004).

One of the most disturbing features of the HIV epidemic in Africa is that much of the transmission is through non-consensual sex. Sexual violence against women as a major means of transmitting the AIDS virus in the changing society of South Africa and its neighbors, where one woman is raped every 95 seconds: Lancet 341: 1340, 1993 (read it; one new national leader says that if a woman is raped, it is her own fault for going out of her house.) Doctors describe the terrible prevalence of rape and "coerced consensual sex" in "the new South Africa": Soc. Sci. Med. 55: 1231, 2002. Another nightmare article: "Infect one, infect all -- Zulu youth response to the AIDS epidemic in South Africa": A widespread, nihilistic "youth culture" (i.e., vicious gangs) actively seeks to infect everyone, especially by raping women (Medical Anthropology 17:363, 1997). Infant rape resulting from a folk belief that this cures HIV infection: Lancet 359: 274, 2002. Mbeki's government specifically reprimands a senior physician for giving AZT to a baby who has been raped: Br. Med. J. 324: 191, 2002. Whatever you decide is the underlying reason for this appalling business (Br. Med. J. 326: 495, 2003 offers a politically-correct analysis that I find altogether unpersuasive), the same thing is going on at comparable levels in nearby countries as well where apartheid was never institutionalized. It makes more sense to me to blame misgovernment of whatever kind, with the resulting poverty, lawlessness, and despair.

As the world rallies to provide antiretroviral therapy for Africa, the drug companies have begun providing regimens at almost no cost, and simplified regimens seem to work (Am. J. Pub. Health 95: 1117, 2005).

* During the early years of the 21st century, the factthat pharmaceutical companies weren't providing free HAART for every AIDS victim in Africa was the subject of a great deal of rhetoric. Left out of the public discussion was the kleptocratic tariffs, taxes, and regulations imposed on these medicines (JAMA 286: 1996, 2001). The World Health Organization's African branch has been blasted by Lancet as totally ineffective because of corruption and incompetence (Lancet 364: 475, 2004). Outside financial aid to Africa from all sources is only about $69 million annually (Lancet 357: 57, 2001); the world is full of people who would like to help but know how hard it is to help effectively given the bizarre politics. Contrary to current fictionalized accounts ("The Constant Gardener"), the big pharmaceutical companies do much less of the HIV research in sub-Saharan Africa than do government and academics, and there's actually disturbingly little work overall (Br. Med. J. 331: 742, 2005).

The world ridicules the Bush Administration's decision to earmark a third of its $15 billion dollar contribution for abstinence-only education: Nature 430: 279, 2004, many others. For me, the most appalling thing about this is the fact that many (most?) girls and women in the poor nations cannot choose abstinence -- they are forced into marriage, or if they do not get a boyfriend they will be raped. For most poor girls in most of the poor nations, "violence and forced intergenerational sex are the norm" (Lancet 364: 303, 2004). This is a sad fact about our world about which we seldom hear in the US. Further, all Bush-administration Federal money going to programs that offer condoms has to include "education about the ineffectiveness of condoms". I am not making this up. The Bush administration is of course playing to its Far Right constituents, here as elsewhere (Nat. Med. 10: 759, 2004). You'll have to decide whether it is good morals, but it's bad science.

How U.S. patients caught AIDS during the first decade (#'s rounded off, 1991 MMWR data):

59%: MSM's
21%: IV drug abusers
7%: MSM's who also do IV drugs
3%: heterosexual contacts of the above
3%: transfusions
1%: hemophiliacs
1%: from Mother
1%: overseas, in areas of "heterosexual transmission"
4%: ???

100%

How U.S. patients are catching AIDS now (CDC online 2004)

42%: MSM's
25%: IV drug abusers
33%: heterosexual contacts, mostly of the above

100%