HIV can be found in blood plasma, peripheral blood mononuclear cells (PBMCs), in bodily fluids and human tissue. Discussion of HIV mutations and drug resistance usually refers to HIV that exists in the blood plasma and PBMCs.

There is considerable viral diversity throughout the body. In people who have been treated during the era of single and two-drug therapy, a mixture of wild-type and resistant virus can often by isolated from various cellular reservoirs even after successful suppression of HIV with triple drug therapy (Noe 2003; Ruff 2002).

A small number of studies have looked for drug-resistant HIV in tissue compartments. One study has found that the HIV genotype obtained from the tonsils (a type of lymph tissue) is very similar to the HIV genotype found in the blood plasma, and although HIV DNA stored in the lymph tissue is archived HIV, it is very similar to HIV RNA in the blood plasma and the lymph tissue. This suggests that lymph tissue is not a source of drug-resistant virus.

Similar research found high concordance of resistance profiles from blood and gut samples. In cases where blood contained 100% mutant virus, gut tissue showed a mix of mutant and wild-type virus (Poles 2001).

Another study found that HIV variants in the blood plasma and the cerebrospinal fluid (CSF), the fluid around the brain, do not differ in untreated people during the early stages of HIV infection. However, a greater variety of naturally occurring mutations was found in 15 untreated people with long-term infection, and there were differences between blood plasma and CSF samples in four of this group. This research suggests that mutations do develop separately in the blood and brain without the selective pressure of drug treatment, and that early treatment may be better able to suppress HIV due to the homogeneity of the virus at this time (Cenci 2000).

A review of paired samples from 31 individuals found that ten out of 31 had evidence of nucleoside reverse transcriptase inhibitor (NRTI)-resistant virus in the CSF, but drug sensitive virus in the blood. Three of the ten patients had high level AZT resistant virus in the CSF, but drug sensitive virus in plasma (Cunningham 2000).

While HIV in the CSF may not contain resistance mutations present in the blood plasma, there is evidence from two people with HIV-related dementia that drug-resistant virus moves from the plasma into the CSF during treatment. This resistant virus quickly takes over from pre-existing virus in the CSF and central nervous system (Wong 1999).

Ongoing research is studying whether limited drug penetration into tissue and other viral compartments contributes to viral resistance. Compartmentalisation of virus within the central nervous system, and the independent of resistance, has recently been demonstrated, with possible implications of HIV-related neurological disease (Smit 2004).

Resistance in the blood does not necessarily mean resistance in the genital tract. A recent study found drug resistance in the blood and vaginal secretions of women with HIV but patterns of resistance differed in the two compartments (De Pasquale 2001). Another group found that drug-resistant HIV in the vagina was likely to be associated with macrophages, thus increasing the risk of transmission of drug resistant virus and reported that virus in blood and vaginal cells may have similar rates of evolution towards resistance (Tirado 2005).

Non-concordance of resistance mutations on HIV in the blood and the semen have also been reported. Of 32 samples, different mutation patterns between the two compartments were found in 46% of patients (Liuzzi 2004).

Compartmentalisation of viral evolution and limited viral diversity has also been observed in the male genital tract, with transmission of viral quasispecies that had been largely outgrown in the blood after stopping treatment (Pillai 2005; Smith 2003).

See Transmission of resistant HIV in Anti-HIV therapy: Resistance and Treating HIV in the genital tract in Anti-HIV therapy: Choosing your treatment strategy for more details.

References

Cenci A et al. Viral dynamics and mutations in the pol gene during primary HIV-1 infection. J Biol Regulators Homeostatic Agents 14: 7-10, 2000.

Cunningham PH et al. Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid. AIDS 14: 1949-1954, 2000.

De Pasquale MP et al. Drug-selected HIV-1 mutations can differ in cervico-vaginal and blood plasma RNA. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 446, 2001.

Devereux HL et al. In vivo HIV-1 compartmentalisation: drug resistance-associated mutation distribution. J Med Virol 66: 8-12, 2003.

Erice A et al. Analysis of HIV-1 reverse transcriptase and protease sequences in paired plasma and lymphoid tissue specimens from HIV-1 infected individuals. AIDS 15: 831-836, 2001.

Liuzzi G et al. Differences between semen and plasma of nucleoside reverse transcriptase resistance mutations in HIV-infected patients, using a rapid assay. In Vivo 18: 509-512, 2004.

Noe A et al. Persistence of resistance genotypes in HIV-1 infected cells after long-term HAART. First European HIV Resistance Workshop, Luxembourg, abstract 18, 2003.

Pillai SK et al. Semen specific genetic characteristics of human immunodeficiency virus type 1 env. J Virol 79: 1734-1742, 2005.

Poles MA et al. Despite high concordance, distinct mutational and phenotypic drug resistance profiles in human immunodeficiency virus type 1 RNA are observed in gastrointestinal mucosal biopsy specimens and peripheral blood mononuclear cells compared with plasma. J Infect Dis 183: 143-148, 2001.

Ruff CT et al. Persistence of wild-type virus and lack of temporal structure in the latent reservoir for human immunodeficiency virus type 1 in pediatric patients with extensive antiretroviral exposure. J Virol 76: 9481-9492, 2002.

Smit TK et al. Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. J Virol 78: 10133-10148, 2004.

Smith DM et al. Male genital tract compartmentalization and transmission of 215L revertant. XII International HIV Drug Resistance Workshop, Los Cabos, abstract 83, 2003.

Tirado G et al. Differential evolution of cell-associated virus in blood and genital tract of HIV-infected females undergoing HAART. Virology 344: 299-305, 2005.

Wong JK et al. The development and trafficking of multidrug resistant HIV in plasma and central nervous system during the failure of combination antiviral therapy. Antivir Ther 4: S76, 1999.