Does methamphetamine affect HIV viral load?

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The viral loads of HIV-positive people who use the recreational drug methamphetamine are significantly higher than those of individuals who do not take the drug, according to research conducted in San Diego and published in the December 15th edition of the Journal of Infectious Diseases. The investigators believe that methamphetamine users have higher viral loads, not because of any interaction between methamphetamine and HAART, but because users of the drug are less likely to adhere to their anti-HIV treatment regimens. However, the evidence is not clear-cut, and another study published recently shows that methamphetamine use appears to exacerbate HIV-related damage to the brain.

Methamphetamine

Methamphetamine is a powerful stimulant. The purest form of the drug, `crystal` or `ice`, will typically keep users high for 18-24 hours, and is either injected or smoked. Use of the drug is widespread in North America, South East Asia and Australia, but it is less common in Europe. In the United Kingdom the vast majority of amphetamine used illegally is amphetamine sulphate, which is less pure and less potent.

Study details

A total of 230 individuals were recruited to the study between 1996 and 2002. Of these, 142 patients participated in a sub-study that looked at viral load in the central nervous system.

Investigators divided the study participants into three categories according to their history of methamphetamine use. Category one comprised individuals who were former users of methamphetamine, category two included patients who had never used methamphetamine, and category three was composed of people who were current users of the drug.

Glossary

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

plasma

The fluid portion of the blood.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

replication

The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

All the patients enrolled in the study had their plasma viral load monitored, and had a comprehensive neuromedical evaluation. A sample of 116 patients had their level of adherence to HAART assessed using a self-completed questionnaire. Investigators also asked individuals if they were using any other recreational drugs.

The use of methamphetamine was significantly related to plasma viral load (p

Investigators then evaluated the potential for interaction between antiretroviral therapy and methamphetamine use, with viral load as the outcome, and HAART status (taking HAART versus not taking HAART), and methamphetamine use (past user, current user, never used), as the variables. The overall result was significant (p

HAART use was further evaluated. The cohort was divided according to the use of HAART, and then further divided according to methamphetamine use. The viral loads of patients not taking HAART were similar regardless of methamphetamine usage (p=0.97). The authors note: "This [finding] is not concistent with a direct biological effect of [methamphetamine] use itself on viral replication."

However, the investigators found that of the patients taking HAART, those who were currently using methamphetamine had significantly higher viral loads (median 5,000 copies/mL), than in individuals who were past users of the drug or had never taken it (median viral loads 1,000 copies/mL). Of the HAART treated patients who had never taken methamphetamine, 62% had an undetectable viral load, compared to 59% of past users of the drug and 39% of current users. These differences were statistically significant (p=0.07).

The investigators found no significant differences in the cerebrospinal fluid viral loads of individuals, regardless of methamphetamine status, even when they restricted their analysis to patients taking HAART. This result is surprising, they say, because animal studies have shown that methamphetamine does stimulate HIV production in brain cells called astrocytes, and also permits infiltration of HIV-infected cells into brain tissue.

The investigators note that stimulant drugs, such as methamphetamine, can increase viral load by dysregulating inflammatory cytokine production. They note that their study found that current users of the drug had higher viral loads than either past users or the drug or patients who had never used the drug, a finding that is consistent with earlier laboratory studies.

However, as viral load was comparable in patients not taking HAART, regardless of methamphetamine use, they believe that poorer adherence to anti-HIV treatment regimens explains the higher viral loads amongst HAART-treated patients who also used methamphetamine. However, they also report that the percentage of patients reporting adherence of at least 95% was comparable regardless of methamphetamine use, and the investigators note in their conclusion that the "response to [antiretroviral therapy] by former meth-dependent persons are similar to those of non-substance abusing control subjects."

The researchers downplay the possibility that a drug interaction between methamphetamine and protease inhibitors might be responsible for the viral load difference, saying that "no consistent reports of altered drug metabolism related to [methamphetamine] use exist," but omit to note that pharmaceutical companies have consistently failed to investigate interactions between pharmaceutical products and illicit drugs, citing the illegality of `street` drugs as a barrier to such research.

Further information on this website

Methamphetamine drastically increases HIV-like virus's ability to replicate in the brain - news story

References

Ellis RJ et al. Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy. Journal of Infectious Diseases 188 (on-line edition), 2003.