HIVAIDS epidemiology, pathogenesis, prevention, and treatment

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• HIV/AIDS epidemiology, pathogenesis, prevention,
  and treatment

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• HIV pandemic
• Pathogenesis of HIV-1
• Clinical management
• Drug treatment
• Prevention
• Conclusions

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HIV pandemic

• An estimated 386 million people live with
  HIV-1 worldwide, while about 25 million have died
  already.
• Today, there is no region of the world
  untouched by this pandemic.

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• Based on their genetic make-up, HIV-1 viruses
  are divided into three groups M main, N, and
  O group.
• These HIV-1 groups and HIV-2 probably result
  from distinct cross-species transmission events.

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Pathogenesis of HIV-1

• Despite its modest genome size (less than
• 10 kb), HIV-1 excels in taking advantage of
  cellular pathways while neutralising and hiding
  from the different components of the immune
  system.

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The structure of HIV-1
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• The HIV-1 life cycle is complex and its
  duration and outcome is dependent on target cell
  type and cell activation.

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The course of HIV-1 infection defined by the
level of viral replication
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• APOBEC3G/3F and TRIM5a are recently described
  intrinsic restriction factors that are
  constitutively expressed in many cells.
• These two proteins have potent antiviral
  activity.

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HIV-1 has evolved strategies to counteract the
restriction factors TRIM5a and APOBEC3G/3F
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Clinical management (Diagnosis)

• Serological tests
• rapid test for surveillance, screening, and
  diagnosis
• little laboratory expertise

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• Limitations
• detection of infection during primary infection
  when antibodies are absent.
• in infants younger than 18 months who
• might bear maternal HIV-1 antibodies.

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• Direct virus detection
• plasma viral load quantification of plasma HIV-1
  RNA copies.
• measurement of CD4 cells reveal the
• degree of immunodeficiency.

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Drug treatment

• Antiretroviral compounds
• Combination antiretroviral treatment
• HAART in resource-constrained settings
• Drug resistance
• Viral reservoirs

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Antiretroviral compounds

• Antiretroviral treatment is the best option
  for longlasting viral suppression and for
  reduction of morbidity and mortality.

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• 20 of the 21 antiretroviral drugs currently
  approved by the US Food and Drug Administration
  target the viral reverse transcriptase or
  protease.

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Combination antiretroviral treatment

• HIV-1s high genetic variability provided the
  rationale for highly active antiretroviral
  treatments (HAART)

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• By combination of several potent
  antiretroviral agents, viral replication is
  suppressed to low levels that emergence of drug
  resistant HIV-1 variants was, if not prevented,
  at least delayed.

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• A set of criteria composed of plasma viraemia
  concentration, absolute or relative CD4 cell
  counts, and clinical manifestations, is used to
  recommend initiation of HAART.

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HAART in resource-constrained settings

• In many countries, treatment options are
  limited not only by the costs of HAART but also
  by restrictive licensing policies.

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• Current estimates suggest that 80 of people
  infected with HIV-1 with a clinical need for
  treatment do not yet have access to
  antiretroviral drugs.

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Drug resistance

• Insufficient compliance, drug side-effects, or
  drug-drug interactions can lead to suboptimum
  drug concentrations, resulting in viral rebound.

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• Drug-resistant HIV-1 is transmissible
• can be detected in up to 20 of newly
• infected individuals in countries with broad
• access to antiretrovirals.

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Viral reservoirs

• HIV-1 latency in long-lived cell populations
  poses an obstacle to eradication because current
  antiviral combination treatments fail to
  eliminate integrated proviruses from resting
  cells.

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Prevention

• Mother-to-child transmission
• Sexual transmission

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Mother-to-child transmission

• Intrapartum transmission has been reduced by
  increasing access to interventions such as one
  dose of nevirapine to mother and newborn baby.

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• Breastfeeding transmission a potential novel
  intervention still being tested is the daily use
  of antiretrovirals during breastfeeding.

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Sexual transmission

• Reduction of heterosexual transmission is
  crucial for control of the epidemic in many parts
  of the world.

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• Prevention is achieved through reduction in
  the number of discordant sexual acts or reduction
  of the probability of HIV-1 transmission in
  discordant sexual acts.

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• Other biomedical prevention interventions
  include male circumcision, antiretrovirals for
  prevention, chemoprophylactic
• treatment of herpes simplex virus-2,
• microbicides, and vaccines.

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• Microbicides
• Microbicides are an additional important
  biomedical intervention technology that is covert
  and under womens control.

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• Vaccines
• A safe, protective, and inexpensive vaccine
  would be the most efficient and possibly the only
  way to curb the HIV pandemic.

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• Recent vaccine development has focused
• on eliciting cellular immune responses.
• This approach is the most promising to
• prevent or at least control retroviral infection.

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Conclusions

• An important gateway to both prevention and
  care is knowledge of HIV-1 status.
• HIV/AIDS is an exceptional epidemic that
  demands an exceptional response.

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• Much progress has been made in a short space
  of time, despite many scientific and programmatic
  challenges.

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• The unrelenting growth of the pandemic tells
  us that current strategies are not enough.
• Needing to do some things differently to
  increase the scale and magnitude of current
  strategies in keeping with the pandemic.

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• Thank you!