Antiretroviral Chemotherapy

Although promising data was presented on new NNRTIs and PIs that are more potent and demonstrate improved resistance profiles, none of them are likely to be available for widespread use within the coming year. Likewise, fusion inhibitors and IL-2 require further study before entering clinical practice. What follows are comments on a few abstracts that deal with simplified preparations or pharmacokinetic (PK) enhancement of existing agents, which are more immediately applicable to clinical care. Full texts of all conference abstracts are available at http://www.retroconference.org/2001.

Abstracts 315 and 316 demonstrated Trizivir's equivalent activity to its components, AZT, 3TC, and abacavir. For selected patients, this offers the simplicity of one pill twice daily .

Abstracts 318 and 319 supported the efficacy of the new extended release formulation of ddI EC as compared to either standard ddI or to other HAART regimens. Enteric-coated Didanosine is easier to take and leads to less drug-drug interactions than standard ddI tablets.

Abstracts 332, 405, and 739 evaluated various dosing regimens for the ritonavir (RTV) enhancement of amprenavir (AMP). Combining data from these studies, the following regimens all appear to have similar efficacy to the standard dosing of AMP 1200 mg bid: AMP 600/RTV 100 bid, AMP 450/RTV 200 bid, and AMP 1,200/RTV 200 or 400 qd. All of the alternative regimens decrease pill burden, increase C min (less opportunity for resistance), decrease C max (less toxicity) and lead to similar AUC. The 450/200 option appears to have the best overall PK parameters, and also obviates the need for dose modification when used with NNRTIs.

Abstracts 334, 335, and 336 studied the PKs of ritonavir enhancement of indinavir (IDV). Pooling data from these three studies, the standard dosing of IDV 800 mg tid had similar PK to IDV 800/RTV 100 bid, IDV 400/RTV 400 bid, and IDV 1200/RTV 200 qd. The bid and qd regimens provided less frequent dosing and eliminated the necessity for dosing on an empty stomach. Overall, the 400/400 option appeared to have the best PK parameters with the least side effects.

Abstracts 18 and 321 provided additional data on the once daily use of emtricitibine (FTC), a NRTI with greater potency and prolonged half-life as compared to 3TC.

In conclusion, virtually every HAART regimen can now be delivered in two daily doses, and there are an increasing number of options for once daily therapies. In the correctional setting, this will increase adherence and simplify directly observed therapy for those systems that chose to use it.

Epidemiology

The following four abstracts demonstrate the overwhelming ongoing need for inmate peer education for all prisoners -- whether known to be infected or not.

• Abstracts 211 (NYC) and 212 (6 U.S. cities) both studied young men who have sex with men (MSM) and found an alarming rate of unprotected anal sex within the past six months (~50% of those interviewed). Both studies also found rates of HIV seropositivity among African American men of approximately 30% -- over twice as high as those from all other racial/ethnic backgrounds.

• Abstract 213 from Los Angeles found that those MSM who had confidence that HAART decreases the risk of HIV transmission were more likely to have had recent unprotected anal sex.

• Abstract 261 from Amsterdam found a marked increased rate of syphilis and gonorrhea (GC) among MSM. Among HIV seropositive MSM, those who experienced a HAART induced rise in CD-4 and drop in viral load were found to then increase their rate of unprotected sex with casual partners.

Transmission

A number of studies have shown that HAART induced drops in HIV viral load decrease the rate of transmission to seronegative partners. Abstract 221 from Thailand corroborated such prior studies by finding no cases of transmission when the HIV viral load was <1,094.

Prior studies have shown that the presence of ulcerative genital disease increases the transmission rate of HIV. Abstract 222 demonstrated that the presence of GC urethritis also markedly increases HIV transmission, reminding us of the unique opportunity that we have in correctional medicine to impact the spread of disease by diagnosing and treating STDs.

Lastly, an important study from the Kaiser HMO system in California (219) evaluated 416 individuals recently diagnosed with HIV. At the time of diagnosis, 44% already had CD-4 <200, with 19% <50. Since HAART is most effective when instituted earlier in the course of the disease (see abstracts 341 and 342), many patients are being diagnosed too late for optimal benefit. Furthermore, 40% of these newly diagnosed individuals had presented with known HIV risk factors at least 12 months before they were eventually tested -- reflecting missed opportunities for earlier diagnosis and treatment. Risk factors included oral infection, pneumonia, unexplained fever >100, herpes zoster, seborrheic dermatitis, night sweats, and unexplained weight loss. Undiagnosed persons not only go untreated, but they also unknowingly pass the virus to others. How often in our own correctional practices have we missed opportunities for earlier diagnosis?

HCV Accelerates HIV and Vice Versa

The impact of HIV on HCV and vice versa has been the subject of much debate. CROI reports contributed to the confusion. In a population of hemophiliacs, Dr Eric Daar found a close linear relationship between HCV RNA level and abnormal liver function tests (SGOT or ALT). The HCV viral load level (by branched-chain DNA) appeared to independently predict an increased risk of HIV clinical progression (abstract 35). This observation was confirmed in a Swiss cohort, described in the Lancet (Greub G, et al. Lancet, 2000;356:1800-1805. However, a report by Sulkowski at CROI contraindicated these findings, suggesting that risk of progression was more linked to lack of access to medical care (for HIV) in his cohort of African American patients who had HIV and HCV coinfection (abstract 34).

*No affiliations to disclose.

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