Reservoirs of resistant virus

HIV can be found in blood plasma, peripheral blood mononuclear cells (PBMCs), bodily fluids and human tissue. Most discussions refer to HIV that exists in the blood plasma and PBMCs. However, viral populations in other bodily tissues (compartments) may serve as reservoirs of resistant virus, and sexual transmission depends on virus in the semen and vaginal tissues.

Antiretroviral drugs themselves reach different concentrations in different bodily compartments: AZT and 3TC have been found at higher concentrations in semen than in blood,1 while PIs do not always appear to reach adequate concentrations in semen. 2

A small number of studies have looked for drug-resistant HIV in different tissue compartments. In people 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.3 4

High similarity has been found between resistance profiles in the blood and in the gut tissue. In cases where blood contained 100% mutant virus, gut tissue showed a mix of mutant and wild-type virus.5

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, differences have been found between resistance patterns in blood plasma and the central nervous system in people with longer-term infection.6 7

Several studies have found varying resistance patterns in the blood and genital tract in women, 8 9 10 and between the blood and semen in men. 11 12 13 11

In addition, two men treated during primary infection had resistant virus in their blood, but undetectable virus in their semen. 10

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. 14

References

  1. Periera A et al. Nucleoside analogues achieve high concentrations in seminal plasma: relationship between drug concentration and virus burden. J Infect Dis 180: 2039-2043, 1999
  2. Taylor S et al. Poor penetration of the male genital tract by HIV-1 protease inhibitors. AIDS 13: 859-860, 1999
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Eron JJ et al. Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission. AIDS 12: F181-F189, 1998
  9. Fang G et al. Complete HIV pol sequence in plasma and genital tract of women: genital reservoir and differential drug resistance. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, abstract I-122, 1998
  10. de Pasquale MP et al. Primary HIV infection: in vivo fitness of pre-therapy resistant mutants and potential for secondary spread of HIV from semen. Antivir Ther 4: S89, 1999
  11. Smith DM et al. Male genital tract compartmentalization and transmission of 215L revertant. XII International HIV Drug Resistance Workshop, Los Cabos, abstract 83, 2003
  12. 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
  13. Pillai SK et al. Semen specific genetic characteristics of human immunodeficiency virus type 1 env. J Virol 79: 1734-1742, 2005
  14. 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
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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